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Acute respiratory infections caused by influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 remain a major public health challenge in Europe. Although surveillance systems for these pathogens are well established, the past 2 decades have seen a rapid diversification of data streams supporting surveillance and research. This expanding data landscape, combined with fragmentation across institutions, sectors, and countries, may limit timely evidence synthesis and effective public health decision-making. This scoping review aimed to identify and characterize data sources used for surveillance and research on influenza, RSV, and SARS-CoV-2 in Europe over the past 20 years, and to examine their evolution over time, their alignment with research objectives, and geographic variation in data availability and use. We conducted a scoping review using an objective-driven analytical framework. Empirical reports published between January 2005 and September 2025 were identified in MEDLINE, Web of Science, and Embase. Eligible reports focused on influenza, RSV, or SARS-CoV-2 and included data from 12 European countries. Clinical and interventional studies were excluded. Reports were classified according to 4 research objectives: epidemiological monitoring, evaluation of interventions, assessment of disease burden and health outcomes, and analyses of population adherence and trust toward public health measures. Data sources were grouped into 9 categories, including surveillance systems, electronic health records (EHRs), registries, claims, surveys, digital, environmental, integrated datasets, and others. A total of 2564 empirical reports were included. Over time, respiratory virus research relied on an increasingly diverse set of data streams. While surveillance systems remained central, particularly for epidemiological monitoring, their relative dominance declined. From 2020 onward, there was a marked expansion in the use of EHRs, registries, claims data, digital sources, and linked or integrated datasets, alongside increased use of open-access data. Data source use varied by research objective: surveillance data predominated in monitoring and intervention evaluation; EHRs in studies of risk factors and treatment effectiveness; surveys in seroprevalence and public trust analyses; and claims data in assessments of economic burden. Substantial geographic disparities were observed. Northern European countries more frequently used linked and multisource datasets, whereas Southern Europe relied more often on open-access or single-source data. This scoping review provides a multipathogen, cross-country mapping of data sources for respiratory virus surveillance and research in Europe over 2 decades, applying an innovative objective-driven framework. Unlike prior reviews focused on single pathogens or data types, it offers a consolidated, comparative perspective based on 2564 reports to inform public health decision-making. The COVID-19 pandemic accelerated innovation in data generation and access, but progress remained largely centered on SARS-CoV-2, while structural fragmentation continues to limit timely, integrated data across Europe. Strengthening preparedness will require interoperable infrastructures, federated analysis platforms, sustainable funding for surveillance innovations, and cross-sectoral data sharing.
Pediatric migrant health has been identified by the World Health Organization as a critical area for interdisciplinary research to improve care for children and adolescents with migration experience. Nevertheless, research agendas have rarely been shaped systematically by individuals with lived and professional experience, limiting relevance and impact. To identify and prioritize the most important unanswered research questions in pediatric migrant health in Europe through a structured, participatory priority-setting process. This multiphase survey study (April 2024 to June 2025), led by migrants and clinicians using the James Lind Alliance participatory priority-setting methodology, comprised 2 online consultations informed by Delphi procedures and a final in-person consensus workshop using a modified nominal group technique. Participants residing in multiple European countries included migrant caregivers, former migrant children and adolescents, health care workers in pediatric migrant health, and double experts with combined lived and professional experience. They were recruited via professional networks, community organizations, and open calls. The final in-person consensus workshop convened in Basel, Switzerland, in June 2025. The primary outcome was a ranked list of the top 10 unanswered research priorities in pediatric migrant health based on participant-generated questions and consensus methods. In consultation 1, 256 participants (156 [61.0%] with lived migration experience; 25 countries of residence, 41 countries of origin; 115 aged <35 years [44.9%], 138 aged ≥35 years [53.9%]; 158 female [61.7%]) submitted 1589 questions and comments, which were consolidated into 53 unanswered summary questions after qualitative content analysis and evidence checking. In consultation 2, rankings from 576 participants (214 [37.2%] with lived migration experience; 31 countries of residence, 50 countries of origin; 193 aged ≤35 years [33.5%], 364 aged ≥35 years [63.2%]; 412 female [71.5%]) yielded a short list of 25 questions. During the final consensus workshop, participants selected the top 10 research priorities. The 3 highest ranked priorities focused on universal access to health care, the health impact of racism and discrimination, and barriers to accessing care. Remaining priorities addressed health effects of migration, social determinants of health, needs of at-risk groups (including unaccompanied or undocumented minors and children with medical complexities), professional language support, training of health care workers, and family involvement in care. The research priorities identified in this survey study could provide a roadmap for future multidisciplinary and participatory research to improve health equity for pediatric migrants in Europe.
To explore the status of low-dose CT lung cancer screening (LCS) training practices, identify existing gaps, and define key competencies to be included in LCS educational curricula. As part of the European SOLACE project, a structured cross-sectional survey consisting of 11 closed- and open-ended items, developed based on relevant literature, international guidelines, and expert input to assess LCS current practices and training needs, was administered to a panel of European LCS experts. Participants were invited to individual Zoom interviews (May-November 2025). Data were analyzed using descriptive statistics. Twenty-five LCS experts were interviewed from 14 European countries, including 10 radiologists (40%), 8 pulmonologists (32%), 4 thoracic surgeons (16%), 1 project manager (4%), 1 smoking cessation specialist (4%), and 1 general practitioner (GP) (4%). Reported training activities ranged from established programmes (4/14 countries), to learning initiatives (6/14) and/or planned programmes (4/14). Radiologists (96%), pulmonologists (80%), and GPs (60%) were identified as the main target groups for training. On a 6-point Likert scale (0 = not important, 5 = extremely important), experts indicated limited awareness of training needs as the most relevant gap (mean 2.8 ± 2.2). Key educational areas to be strengthened included management of incidental findings (4.5 ± 0.6) and confident use of guidelines for nodule management (3.8 ± 1.8). Among essential competencies for professionals involved in LCS, the highest-rated were competence in managing incidental findings (4.7 ± 0.6), familiarity with guideline-based nodule management (4.7 ± 0.6), basic knowledge of AI tools (4.5 ± 0.8), and communication with LCS participants (4.5 ± 1.1). The findings suggest a heterogeneous LCS training landscape across European countries and underscore the importance of developing shared European curricula. Key priorities may include strengthening technical skills alongside structured communication training. Education and training of all stakeholders are essential for the successful implementation of LCS programmes. This survey assesses the current status of LCS training practices across Europe, identifies existing gaps, and defines key competencies to inform future curricula for health professionals involved in LCS. The European LCS training landscape is highly heterogeneous, with substantial variability in training activities, target professionals, and delivery modalities.
Revitalization measures currently represent an important tool in ecological practice for the recovery of disturbed habitats, and their effectiveness is increasingly assessed using bioindicator groups, including ground beetles (Carabidae). Between 2020 and 2023, we conducted research in the European habitat of the Danube Floodplains, where we evaluated the impact of revitalization measures on ground beetle assemblages. The study was carried out at 15 study sites representing eight habitat types. At each site, five pitfall traps were installed in a linear arrangement. In total, 5,292 individuals belonging to 47 species were analyzed, with a mean ellipsoid biovolume of 192 mm3 per individual. PCA analysis revealed a division of species into two main clusters according to their preference for forest and open habitats, with reference sites without management characterized by a higher proportion of apterous and brachypterous species. In contrast, habitats subjected to restoration measures showed dominance of macropterous species typical of disturbed and dynamic ecosystems. Significant differences in ellipsoid biovolume and all morphometric traits were confirmed among habitats and study years. Habitats with restoration measures exhibited a gradual increase in ellipsoid biovolume and morphometric traits of individuals, indicating improved food availability and more favorable living conditions. Prediction of ellipsoid biovolume development using LSTM models (neural networks) indicated stabilization of Carabidae assemblages in forest habitats after the completion of restoration measures, whereas pronounced fluctuations persisted in open habitats, suggesting the need for a longer time period or more intensive interventions to achieve community stability. The results provide a practical basis for planning and evaluating the effectiveness of restoration and management measures in European habitats of conservation importance, as well as for biodiversity conservation and adaptive landscape management, particularly in optimizing interventions in forest and open ecosystems to achieve long-term stability of Carabidae assemblages.
Kawasaki disease (KD) is a childhood vasculitis affecting medium-sized arteries, particularly the coronary arteries. Despite treatment with intravenous immunoglobulin (IVIG), coronary artery aneurysm (CAA) rates remain high in Europe and North America. The KD-CAAP trial evaluated whether adjunctive prednisolone reduces CAA in unselected European children with KD. This multicentre, randomised, open-label, blinded endpoint-assessed, superiority trial (ISRCTN71987471) enrolled children aged 30 days to 16 years across 59 centres in 12 European countries. Participants were randomised 1:1 to oral prednisolone (2 mg/kg/day) plus IVIG (2 g/kg) and aspirin (experimental group); or IVIG and aspirin (control group), stratified by age (<1 vs ≥1 year), sex and country. Co-primary outcomes were: CAA within 12 weeks and mean maximum coronary artery z-score across weeks 1-6, analysed using intention-to-treat. Between Jan 2021-July 2024, 103 children (58% male; median age 2 years) were randomised: 50 to experimental and 53 to control groups. All children received IVIG + aspirin; fewer experimental participants received a second IVIG dose [9 (18%) vs 20 (38%) control, p = 0.021] or rescue therapy [8 (16%) vs 17 (32%), respectively, p = 0.044]. CAA occurred in 12/50 (24%) experimental vs 12/53 (23%) control participants (adjusted risk difference +1.1% (95% credibility interval -13.8%-16.1%), with 45% probability of benefit. There was no evidence of difference in mean maximum coronary z-scores over weeks 1-6 (mean 0.6 (95% confidence interval 0.4-0.9) vs 0.7 (0.4-0.9); adjusted difference -0.0; 95% confidence interval -0.2 to +0.2; p = 0.72). CAA developed in 6/12 (50%) infants <1 year. Serious Adverse Events occurred in 7 (14%) experimental vs 3 (6%) control participants (p = 0.19). Costs were significantly lower in the experimental group due to less IVIG use over 12 weeks. Prednisolone reduced treatment escalation, with potential health economic benefits, but did not reduce CAA in unselected European children with KD. CAA rates remained high, particularly in infants. Innovative Medicines Initiative grant 777389.
Widespread municipal and industrial feedstocks rich in organics are potential feedstocks for allocating biogenic carbon into circular bioproducts through open-culture biotechnology. In this work, we estimate the production potential of selected biochemicals (methane, lactate, medium-chain carboxylates [MCC]) and biopolymers (extracellular polymeric substances [EPS]; namely flocculant EPS and alginate-like EPS [ALE], and polyhydroxyalkanoates [PHA]). Theoretical and practical carbon and chemical oxygen demand (COD) efficiencies are presented to estimate their bioproduction potential in Europe (EU-27) based on a meta-analysis, feedstock-bioproduct compatibility assessment and Monte Carlo simulations. Potentially compatible feedstocks added up to about 60 and 20 Mton/year of COD and carbon, respectively, and comprised municipal wastewater, food waste and industrial wastewaters from the food (dairy, beverages, yeast and sugar) and pulp and paper (pulp, cardboard) sectors. Methane, a highly reduced molecule (oxygen/carbon ratio = 0), is the bioproduct that can recover the most COD (∼36 Mton COD/year) and carbon (∼7 Mton carbon/year) from the feedstocks, whereas oxygen-rich lactate (O/C = 1) showed the highest mass flux potential (∼12 metric Mton/year). From the biopolymers, flocculant EPS had the highest bioproduction potential (∼11 Mton COD/year). The estimated potentials could supply a significant fraction of the global market demand for e.g., plastic applications from lactate and PHA; or European targets for e.g., biomethane or sustainable aviation fuels (SAF) from MCC. A supply potential of EPS-based products in excess of their market applications demand indicate that further market development may be required. This study illustrates the opportunities for future commercialization of open-culture bioproducts.
Introduced in 2020, plain language summaries of publications (PLSPs) are standalone articles that aim to expand the reach of scientific findings to non-specialist audiences using plain language and meaningful visuals. Despite increased publication, there is no agreed cross-publisher definition of PLSPs, resulting in inconsistent terminology, formatting, peer-review processes, and metadata that hinder indexing and discoverability in bibliographic databases such as PubMed and Europe PMC. In February 2024, the multistakeholder collaboration Open Pharma launched an initiative to review existing standards and practices related to the publication of PLSPs. After identifying three publishers offering standalone PLSPs - Becaris Publishing, Sage, and Taylor & Francis - representatives from each formed a steering committee to define PLSPs and agree on principles that differentiate them from other publishing formats. PLSPs are defined as standalone summaries of peer-reviewed articles, written according to plain language principles, published open access with a unique digital object identifier (DOI), and are themselves peer reviewed (including by someone who is not a scientific specialist in the topic area). They should include a summary, clear reference to the original article, and a combination of text and meaningful graphics. This consensus provides a foundation for standardizing PLSPs as a distinct article type and acceptable secondary publication format. We hope it will also support consistent authoring, editorial management, peer-review processes and indexing. We call on indexing services to formally recognize PLSPs and on publishers to adopt this format as an accurate and reliable source of understandable scientific information. First introduced in 2020, plain language summaries of publications (PLSPs) are a type of scientific research article that take complex research and translate it into clear, simple language and visuals to make the key findings easier to understand. PLSPs are becoming more popular. However, even the most popular online libraries of research articles (also called research databases) don’t have specific filters to search for PLSPs, which makes them hard to find. To fix this, Open Pharma launched a project in 2024 to create a standard definition for PLSPs. They worked with three publishers that publish PLSPs – Becaris Publishing, Sage, and Taylor & Francis – to agree on the content of PLSPs and how they should be published. Together, they agreed that PLSPs are easy-to-read summaries of research articles. They should include easy-to-understand text and graphics, clearly link to the original article, be free to access online, and have their own unique identifier (called a digital object identifier [DOI]). They should be reviewed by scientific experts and people with lived experience (a process called peer review) to make sure the PLSP is accurate, understandable and fit for purpose. We hope that this agreement will help PLSPs become a recognized article type, and – with action from research databases and other publishers – could make them easier to find.
Transition of extracellular vesicle (EV) research from basic discovery to clinical application raised hopes regarding diagnostic, therapeutic and prognostic progress. Rigorous reporting of experimental details is required to align the EV field with pharmaceutical quality standards. MISEV2023 recommendations encourage concise reporting but widespread adoption remains limited. Current reporting tools are time-consuming, and adherence declines despite rapidly growing number of EV studies. We therefore created EV-Checklist, a complementary digital tool that streamlines reporting and increases transparency. By uploading manuscript text, an AI-assisted algorithm automatically completes a checklist covering EV nomenclature, source, isolation, characterization and function. To ensure accuracy, users validate AI-generated entries before submission-ideally, gaps in reporting can be closed (e.g., missing particle/protein ratio). The resulting concise report can accompany manuscripts helping editors, reviewers and readers by presenting key methodological and results details at a glance. EV-Checklist complements existing comprehensive registries as 'fast-and-easy' tool enhancing clarity and accessibility of EV research data and may promote higher adherence to documentation standards. Adoption may be encouraged by journal endorsement to streamline the review process for compliant submissions, signalling adherence to MISEV2023 standards. EV-Checklist and an accompanying AI-assisted search tool (PMC EV Search), spanning over 45,700 open-access EV manuscripts, are publicly available at https://ev-zone.org/.
The transition to electrified drivetrains fundamentally reshapes material demand and future secondary raw material supply. However, existing vehicle composition data are often fragmented or proprietary. This study presents a harmonized, open-access dataset detailing the material and elemental composition of the European passenger car fleet (M1 category) from 1980 to 2050. Using integrated top-down and bottom-up methodologies, we provide high-resolution data for six drivetrain types and 13 vehicle segments, including crossover utility vehicles and battery-electric models. The dataset links products, components, materials, and elements (p-c-m-e), with standardized alloy specifications and quantified uncertainty. Technical validation confirms high internal consistency, with Pearson correlation coefficients (r) between independent modeling approaches exceeding 0.96 for total metal, aluminum, and iron/steel content. This dataset supports robust stock-and-flow modeling and recoverability analysis beyond mass-based indicators. By aligning with emerging regulatory tools like Digital Product Passports, it enables evidence-based resource strategies and circular economy planning for critical and strategic raw materials.
The Stratification of Patients Using Advanced Integrative Modelling of Data Routinely Acquired for Diagnosing Rheumatic Complaints (SPIDeRR) project aims to improve the patient journey for individuals with musculoskeletal (MSK) complaints due to rheumatic and musculoskeletal diseases (RMDs). The primary objective was to understand patients' experiences navigating the healthcare system to achieve timely diagnosis and treatment for RMDs. Secondary objectives included identifying challenges and opportunities for implementing digital tools for help seeking and diagnosis, thus enhancing access to appropriate treatments. Based on the patient experience mapping framework, 3 substudies were conducted as follows: (i) a systematic review and stakeholder surveys to identify key stages and touchpoints; (ii) focus groups to gather additional insights; and (iii) synthesis of findings into visual maps and personas highlighting gaps and potential solutions. Substudy 1 (36 studies and 247 survey participants) revealed that navigating the healthcare systems in Europe is complex, facing significant barriers, such as limited specialist access, knowledge gaps, and inconsistent treatment pathways for people with RMDs. Substudy 2 (28 participants with and without RMDs) found that initial symptom management may delay proper care, multiple emotions emerge while waiting for a solution, and preferences for direct specialist access vs general practitioner gatekeeping vary depending on individual and healthcare system. Substudy 3 developed visual representations of 5 evocative patient journeys, outlining stages, obstacles, interactions, and emotions. The journey of Europeans with MSK complaints is intricate and country specific, posing challenges for nontailored solutions. Personalised digital tools, improved healthcare provider education, and efficient communication between care levels are recommended to enhance the patient experience and improve outcomes for individuals with RMDs.
An enhanced understanding of eosinophilic granulomatosis with polyangiitis (EGPA) in clinical practice may help identify areas where patient management could be improved. The objectives of this study were to examine the real-world demographics, patient diagnostic journey, disease burden, treatment patterns, and health-related quality of life (HRQoL) of patients with EGPA. Data were drawn from the Adelphi Real World EGPA Disease Specific Programme, a cross-sectional survey of patients with EGPA and their physicians in Europe (France, Germany, Italy, Spain, and the UK) and the USA from July to December 2023. The study included 121 physicians and 503 patients. Most patients were White (89%), the mean (SD) age was 49.5 (15.3) years, and the distribution of sexes was balanced. Mean (SD) time between sign/symptom onset and EGPA diagnosis was 9.8 (19.1) months. Patients had a mean (SD) of 5.5 (3.8) signs and/or symptoms at diagnosis, and physician-perceived severity of EGPA was mild in 20%, moderate in 55%, and severe in 24% of patients. Glucocorticoids were the most prescribed therapies (79%), and the use of interleukin-5-/receptor alpha-targeted therapies was low (21% mepolizumab, 7% benralizumab, <1% reslizumab). Patient-reported HRQoL and work productivity were most impacted in those with organ damage, oral glucocorticoid dose ≥10 mg/day, blood eosinophil count ≥300 cells/μL, or relapse, refractory, deteriorating, moderate, or severe disease. EGPA is associated with a considerable disease burden. Increased disease awareness to facilitate prompt diagnosis and treatment and optimised management to achieve remission and enhance patients' HRQoL are needed.
Medical education research acknowledges "P2P-teaching" as an effective, scalable, and cost-effective possibility for educating students in human medicine. At the same time, the medical field is yet to form an empirically founded and overarching description of necessary P2P-teaching competencies across medical subjects. In order to create an overarching picture of relevant student P2P-teaching competencies in medical education, this article raises the question, "What are the relevant teaching competencies in qualification measures for P2P-teachers in medical education?". We performed a systematic mapping review. Our search strategy applied the PICOS-Scheme and the semantic fields "student tutor", "qualification", "competency", "medical" and "empirical" to medical and educational databases, over the period from July to November 2024. A snowballing-system enriched the results, and a selection process according to PRISMA systematically reduced search results from 322 down to 18 peer-review articles for in-depth analysis. This final sample includes peer-reviewed studies from North America, Europe and Australia, drawing from many medical disciplines and published in English and German. For synthesis, we extracted key study characteristics and qualitatively analyzed contents of qualification measures for P2P-teachers. The analysis brings three medical and 12 student P2P-teaching competencies to the fore. Together these competencies form a competency-profile for student P2P-teachers. The competency-profile shows overlaps with relevant medical teaching frameworks. The relevant studies not only show a weak grounding of P2P-teaching research in learning and teaching theories, but also that they tend to be limited to low levels of evidence. Our results are limited to the peer-reviewed and English- and German discourse. This specific discourse on P2P-teaching does not show an overarching consensus as to what the focal competencies for student P2P-teachers are, but it shows a remarkable number of implicit and explicit overlaps. Therefore, the P2P-teaching competency-profile for student tutors might serve as a starting point for (and invitation to) an open-discussion across medical schools to create and elaborate on an interrelated evidence-based research strategy on P2P-teacher-training. Against the background of the current state of research methodology, systematically investigating competencies of student P2P-teachers is a fruitful research area.
With growing interest in ART, fertility preservation, and postmenopausal health of women, reproductive medicine is increasingly focused on characterizing oocytes and ovarian tissue composition, as well as understanding the molecular mechanisms that guide ovarian function throughout its lifecycle. High-throughput omics technologies have enabled the characterization of different molecular layers, leading to substantial advances in our understanding of their complex dynamics. However, not all molecular aspects are studied equally, and studies examining the same modalities often show inconsistencies, underscoring the need for data standardization and highlighting the potential for using transformative artificial intelligence and machine-learning (AI/ML) methods for ovary studies. This study aims to evaluate how multi-omic studies have advanced our understanding of the ovarian lifecycle from fetal development to postmenopause. We systematically reviewed published studies that have investigated molecular/omic layers, including the genome, methylome, transcriptome, and proteome throughout ovarian development and aging. Our analysis identified key molecular and cellular patterns, highlighted inconsistencies across studies and addressed gaps in data analysis, interpretation, and reproducibility to guide future research. We conducted a systematic literature search of Medline (PubMed), Embase (Ovid), and Web of Science Core Collection (Clarivate) using a combination of controlled and free text terms for human ovary, oogenesis, folliculogenesis, ovary development and (epi)genome, transcriptome, proteome, and multi-omic mechanisms to find relevant articles published before August 2025. To focus the scope of the current review, studies of domesticated and farm animals, rodents and other model organisms, non-human primates, as well as those examining various human ovarian pathologies were excluded. The search identified 23 546 studies for screening, of which 637 full-text studies were assessed for eligibility. Subsequently, we extracted data from 121 studies. Most studies analyzed the transcriptome of oocytes, granulosa cells, and ovarian tissue from reproductive-age individuals (n = 91), with fewer studies examining samples from individuals of advanced reproductive age (n = 45) and fetal (n = 16) samples. Transcriptome analyses were most common (n = 103, 85%), followed by proteome (n = 19, 16%) and epigenome (n = 14, 12%) studies. We found substantial variation in how studies defined and reported participants' groups as well as in their sequencing technologies and data analysis methods, with a lack of standardized reporting of background clinical information, data analysis methods, and pipeline details. The key findings underscore the prevailing consensus on genes defining major ovarian cell types and their roles throughout the ovarian lifespan, from prenatal development to postmenopausal transformation. This review highlighted the underrepresentation of certain patient groups, particularly prepubertal and peri-/postmenopausal individuals, among researched populations, due to obvious clinical and ethical reasons. This scoping review offers a comprehensive overview and benchmark of the current state of high-throughput omics-based research on ovarian cellular composition and molecular dynamics. To address these shortcomings, we propose general recommendations for multi-omics ovary studies and emphasize the necessity for more thorough multi-omic data integration by effectively applying novel AI/ML approaches. They can potentially improve the quality of multi-omics analyses at both single-cell and tissue levels despite limited sample sizes and enable integration of molecular profiling data with clinical and radiology datasets, enabling a more comprehensive understanding of ovarian biology. Such advancements can enhance reproducibility of research findings and guide future research to deepen our understanding of ovarian biology and ultimately support the development of medical technologies for better preserving fertility and alleviating infertility. A protocol was published a priori on the Open Science Framework (https://osf.io/z38gb/).
Antibody-mediated rejection (AMR) is a major cause of kidney transplant failure. The CD38 antibody felzartamab has been shown to reduce AMR activity, but recurrence after stopping treatment suggested a need for sustained therapy. We extended a placebo-controlled phase 2 trial (NCT05021484) to assess the feasibility and durability of prolonged, biomarker-guided treatment. Of the 21 patients who completed the primary study, eleven patients with recurrent or persistent AMR after treatment discontinuation received felzartamab for an additional 12 months (16 mg/kg IV): 6 months of fixed dosing followed by 6 months of donor-derived cell-free DNA (dd-cfDNA)-guided dosing. Endpoints included biopsy findings, dd-cfDNA, donor-specific antibodies (DSA), natural killer (NK) cell dynamics, urinary chemokines, kidney function, and safety. Felzartamab (median of two doses during the biomarker-guided phase) was associated with changes in rejection activity and stable kidney function. Median microvascular inflammation decreased from 2 (IQR 2-2) to 0 (0-2) at week 52, with 7 of 11 patients (64%) showing a score of 0; one developed low-grade intimal arteritis. Molecular AMR probability declined from 0.77 (0.58-0.87) to 0.12 (0.08-0.35). Overall, dd-cfDNA, NK cells and chemokines decreased, whereas DSA remained largely unchanged. Treatment was well tolerated, with mild-to-moderate infusion reactions and no treatment discontinuations. Re-dosing and prolonged CD38 targeting was associated with lower AMR activity in most patients despite heterogeneity, supporting AMR as a chronic process that may benefit from ongoing immunomodulation. dd-cfDNA-guided dosing was feasible, with variable dose requirements and effects. Larger and longer trials are required to determine optimal dosing and long-term benefit. Biogen (unrestricted grant). Insight (in kind dd-cfDNA measurements).
Older adult care systems face severe workforce shortages, rising demands, and high levels of stress and burnout, undermining the quality of care and organizational resilience. Support4Resilience (S4R, 2024-2028) aims to improve working conditions and mental well-being by equipping leaders with an evidence-based, organizational-level intervention. The project develops and evaluates a digital S4R Toolbox consisting of 3 tools: (1) mapping and identification (MAP); (2) reflection and education (IMPROVE); and (3) reorganization (REMOVE). The project aims to strengthen resilience and mental well-being among health care workers and informal caregivers in older adult care across Europe and Australia through the development and implementation of the digital S4R Toolbox. Secondary objectives are identifying determinants of resilience and mental well-being across diverse contexts; exploring needs and perspectives that inform successful adaptation to changing working conditions and ethical challenges; designing the S4R Toolbox; evaluating its relevance, effectiveness, and cost-effectiveness across health care systems; advancing theory on the relationship among individual resilience, organizational resilience, and leadership; and producing research-based recommendations and interventions through the open-access S4R Resource Bank. S4R applies an exploratory, longitudinal, mixed-methods co-design approach across 4 phases. The input phase gathers evidence through literature reviews, context mapping, and qualitative and quantitative data collection in 7 countries. The co-design and prototype testing phase involves developing the S4R Toolbox and conducting pilot testing. The implementation, evaluation, and finalization phase includes a 1-year implementation period, followed by process, effectiveness, and cost-effectiveness evaluations and final refinement of the Toolbox. The output phase disseminates the results through the open-access S4R Resource Bank. The project has achieved substantial early progress, including 5 literature reviews, completed and published context mapping, and comprehensive data collection involving health care workers, leaders, and informal caregivers in 7 countries. Toolbox development is well advanced, and pilot testing has been completed. S4R will deliver a research-based digital Toolbox that supports leaders in strengthening the resilience and mental well-being of health care workers and informal caregivers in older adult care. By integrating the perspectives and experiences of leaders, health care workers, and informal caregivers, identifying resilience factors, and developing theory-informed, cost-effective interventions, S4R will provide actionable resources through an open-access platform, contributing to more resilient older adult care systems. ClinicalTrials.gov NCT07504042; https://clinicaltrials.gov/ct2/show/NCT07504042. DERR1-10.2196/73701.
The genetic architecture of Parkinson's disease varies considerably across ancestries, yet most previous genetic studies have focused on individuals of European ancestry. We aimed to characterise the distribution of established Parkinson's disease causal variants, as well as risk-associated variants with clinical implications (ie, variants in genes involved in pathways targeted by ongoing clinical trials), across ancestrally diverse populations. We conducted a multi-ancestry, observational, cross-sectional genetic study using retrospective data from the Global Parkinson's Genetics Program (GP2) release 11 (released in December, 2025). The study investigated causal and risk variants, including copy number variants, in established Parkinson's disease and parkinsonism-associated genes, following the recommendations of the Movement Disorder Society (MDS) Task Force on the Nomenclature of Genetic Movement Disorders, including GBA1, LRRK2, SNCA, VPS35, RAB32, PINK1, PRKN, PARK7, ATP13A2, DCTN1, DNAJC6, FBXO7, JAM2, RAB39B, SLC20A2, SYNJ1, VPS13C, and WDR45. Individuals with Parkinson's disease were diagnosed based on established clinical criteria, including the Parkinson's UK Brain Bank or MDS diagnostic criteria (or both), and healthy control participants were defined as individuals without evidence of neurodegenerative disease and unrelated to participants with Parkinson's disease. We analysed genome and exome sequencing and array genotyping data of 99 783 individuals, including 58 559 individuals with Parkinson's disease and 41 224 controls, from 11 genetically inferred ancestries (African, African admixed, Ashkenazi Jewish, Latino and Indigenous people of the Americas, central Asian, complex admixture, east Asian, European, Finnish, Middle Eastern, and south Asian), defined using reference population-based ancestry inference methods. We calculated allele frequencies for all investigated variants in individuals with Parkinson's disease and controls, both overall and stratified by ancestry. Approximately 29% of individuals (29 001 of 99 783; 15 443 [26·4%] of 58 559 individuals with Parkinson's disease and 13 558 [32·9%] of 41 224 controls) were from under-represented populations (ie, non-European and non-Ashkenazi Jewish). Our findings indicated both shared genetic contributors across ancestries as well as ancestry-specific differences in variant frequencies and the spectrum of variants within Parkinson's disease-associated genes. Overall, 1217 (2·1%) of 58 559 individuals with Parkinson's disease carried a causal variant, with substantial variations across ancestries ranging from ten (0·4%) of 2844 African individuals to 251 (10·7%) of 2343 individuals of Ashkenazi Jewish ancestry. Risk variants in GBA1 and LRRK2 were identified in 6893 (11·8%) of 58 559 individuals with Parkinson's disease and 3578 (8·7%) of 41 224 controls. GBA1 risk variants were most frequent overall and identified across all ancestries, but variant frequency and spectra differed substantially between ancestries, from 195 (4·1%) of 4773 in the east Asian ancestry group to 1505 (52·9%) of 2844 in the African ancestry group. Similarly, LRRK2 causal and risk variants showed ancestry-specific enrichment, with the highest frequencies of causal variants in the Ashkenazi Jewish (250 [10·7%] of 2343) and Middle Eastern (59 [4·4%] of 1347) ancestry groups, whereas risk variants were predominantly identified in the east Asian ancestry group (601 [12·6%] of 4773). Carriers of biallelic causal variants in PRKN, commonly including deletions and duplications, were also identified across all ancestries except Ashkenazi Jewish; the highest frequency was in the Middle Eastern ancestry group (17 [1·3%] of 1347), and frequencies in all other ancestries were less than 1%. This large-scale, multi-ancestry genetic study offers crucial insights into the population-specific genetic architecture of Parkinson's disease. Whereas clinical trials targeting GBA1 and LRRK2 variant carriers are primarily performed in Europe and the USA, increased ancestral diversity in Parkinson's disease research will be crucial to improve diagnostic accuracy, enhance our understanding of disease mechanisms across populations, and ensure equitable application of and access to emerging genetically informed therapies. Aligning Science Across Parkinson's (ASAP) through the Global Parkinson's Genetics Program (GP2).
Climate change is accelerating the circulation of the chikungunya virus (CHIKV), posing a significant threat to both endemic areas and immunologically naive temperate regions. This study aims to synthesize empirical climatic drivers, future transmission projections, and global adaptation strategies to evaluate current evidence and identify key research gaps. This scoping review completed protocol registration on the Open Science Framework prior to literature retrieval, with systematic searches conducted across PubMed, Web of Science, Scopus and EBSCOhost to collect all relevant English peer-reviewed papers published between Jan 1, 2000 and Nov 1, 2025. Multi-level screening filtered out unqualified literature, and unified datasets related to epidemiological parameters, predictive models and adaptation measures were extracted from 104 eligible studies. The results indicate that: (1) Current evidence reveals post-2014 research favors Europe and South America, disproportionately focusing on temperature (n = 38) and precipitation (n = 32). CHIKV transmission exhibits a non-linear thermal optimum (23-30 °C) and a 1-to-4-week lag following extreme precipitation. (2) Future projections (n = 24) consistently indicate transboundary vector expansion into higher latitudes and altitudes. (3) Regarding adaptation strategies, we conceptualized a three-tiered intervention framework. However, a stark socioeconomic-climatic gap emerged: while 43% of the research centers on mid-tier early warning systems in high and upper-middle-income nations, evidence for the foundational infrastructural resilience in low-income regions is limited. This global climate-CHIKV synthesis reveals structurally imbalanced preparedness. To mitigate escalating transboundary risks, international health policies must pivot from solely reactive surveillance. Future priorities should include proactive, climate-resilient urban infrastructure and equitable cross-border coalitions in neglected low-resource settings.
Rectal cancer treatment in Nordic countries has traditionally differed, especially regarding neoadjuvant treatment. The aim of this review is to give an overview of the current rectal cancer guidelines in the Nordics and compare these to international guidelines. Oncologists and colorectal surgeons from the Nordic countries (Denmark, Finland, Norway, and Sweden) and the Netherlands were invited to participate in this narrative review. Two consensus meetings were held to agree on the content. All authors provided recommendations from their national guidelines. In addition, recommendations from the European Society of Medical Oncology (ESMO) and from the US National Comprehensive Cancer Network (NCCN) guidelines were extracted. Several differences between the included guidelines were identified. The radiological "sigmoid take-off" definition for the upper margin of the rectum has been adapted in Denmark and the Netherlands, whereas the other guidelines rely on distance from the anal verge on rigid sigmoidoscopy. Indications for direct surgery vary considerably, where the NCCN guidelines recommend more aggressive neoadjuvant treatment, primarily total neoadjuvant therapy (TNT), the Nordic and European guidelines open for direct surgery more often, and reserve especially TNT for high-risk cases. European countries more often recommend short-course radiotherapy, whereas NCCN maintains chemoradiotherapy as the mainstay. Whereas intentional and opportunistic organ preservation is an established part of the Dutch, NCCN, and ESMO guidelines, its use is mostly restricted to clinical trials in the Nordics. The Nordics and the Netherlands are restrictive in terms of adjuvant treatment, which is frequently recommended in ESMO and NCCN. Whereas neoadjuvant immunotherapy is recommended for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer in NCCN, this use is off-label in Europe and not routinely recommended. Although all guidelines rely on the same evidence, there are considerable differences, especially in the indications and type of oncologic treatment, both in the neoadjuvant and in the adjuvant setting.
We report the first study of anumigilimab, a novel anti-G-CSFR antibody, in patients with neutrophil-driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)]. This phase 1b, open-label, repeat-dose study (NCT03972280) comprised 15-week treatment and 9-week follow-up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21-day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment-emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response. Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab-related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment-related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal-finding exploratory analyses, 57.9% of patients with HS (n = 11/19 with data at Week 15) achieved ≥50% HS Clinical Response, IHS4 score decreased by 40.3%, and patients with PPP experienced a 40.4% reduction in ppPASI score. These clinical responses were not dose dependent, possibly due to imbalanced baseline characteristics and small sample size. Anumigilimab was generally well tolerated in patients with HS or PPP, with no serious treatment-related safety concerns, and demonstrated dose-dependent pharmacology. While clinical responses in HS and PPP were observed, it should be noted that these observations were exploratory and signal-finding in nature. Importantly, the study was not powered to statistically confirm efficacy and lacked a placebo control, underscoring the need for future randomized, placebo-controlled trials to validate these preliminary signal-finding observations. Hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP) are skin diseases that substantially affect patients' lives. Inflammation is a normal response to injury or infection. But inflammation can sometimes occur without injury or infection, resulting in long‐term diseases such as HS and PPP. A molecule called granulocyte colony‐stimulating factor (G‐CSF) drives inflammation in HS and possibly PPP. Blocking G‐CSF therefore may have the potential to improve symptoms. A novel drug called anumigilimab blocks the activity of G‐CSF. We used anumigilimab to treat 39 participants with HS or PPP in Australia and Europe. Our main goal was to see whether anumigilimab has any unwanted effects. Participants received 5five injections of anumigilimab, which were given every 3 weeks. Anumigilimab was not associated with any serious safety concerns. Sixteen patients had unwanted effects related to anumigilimab, which cleared up by themselves. The most common of these were tiredness and low levels of neutrophils (a type of white blood cell). Anumigilimab levels in blood, and its effects on neutrophil levels, were proportional to the amount of drug given. Several participants with HS or PPP appeared to benefit from receiving the drug. In conclusion, our results suggest that anumigilimab may be able to benefit people with HS or PPP. However, a placebo was not used in this small study. Anumigilimab requires investigation in larger studies with a placebo in order to further determine its safety and effectiveness.
In protected areas, fragmentation and artificial light at night are usually present alongside changes in land type, from natural to agricultural or urban. We explored the intensity of edge effects on light trap responses of nocturnal insects at the margin of the floodplain forest in the Donau-Auen National Park in Central Europe, Austria. Specifically, we examined the abundance and biomass of nocturnal insects and characterized the community composition and diversity of moths with respect to the local habitat. In this study, 58 species were observed, with 21 unique records on the forest edge and nine in the interior. Traps in the forest interior harbored significantly higher nocturnal insect biomass. However, moth assemblages were more diverse at edge sites due to many singletons, attributed to individuals attracted from areas with open vegetation. Nine species (15.5% of total) were recorded later than expected given their summer flight periods, potentially reflecting the effects of ongoing climate change associated with warmer autumns. Overall, we observed higher moth species diversity at the forest edge, and insect biomass and moth abundance were higher within the forest. These findings underscore the urgent need to incorporate local anthropogenic landscape and climate change as synergically evolutionary drivers in future population and community-focused research.