Aims: Chemokines are inflammatory mediators during acute and chronic liver injury. The chemokine PF4 (CXCL4) is the only chemokine which is mainly secreted by platelets. PF4 has been shown to interact with RANTES (CCL5), thereby increasing monocyte arrest to endothelium. As RANTES has been shown to stimulate hepatic stellate cells and platelets are thought to contribute to liver fibrosis, PF4 might be an interesting novel mediator of liver injury.

This present deliverable, D3.2 “Interdisciplinary Collaborations between EATRIS and other Research Infrastructures” builds on EATRIS-CONNECT D3.1 which describes the Life Science domain through a translational lens connecting researchers, patients, the data lifecycle and healthcare interventions. It presents a blueprint for connecting European research infrastructures (RIs) across domains to accelerate the development of personalised medicine (PM). The main outcomes of this deliverable are:1. A conceptual model of an Interdisciplinary Research Graph linking data, services, and expertise across domains for the advancement of PM.2. A proof-of-concept prototype demonstrating how a graph can be structured and queried.3. Two use cases (pancreatic cancer; environmental exposure and childhood cancers) illustrating the value of such a graph in identifying partners, mapping services, and exposing gaps. Key findings: •Interconnecting diverse infrastructures reveals new opportunities for research on complex health challenges where biology, environment, and social determinants intersect.•The graph can serve as a navigation tool for researchers and policymakers to discover services and build collaborations, while also supporting funding proposals with a structured interdisciplinary narrative.•Important gaps remain, including limited coverage of artificial intelligence (AI)/machine learning (ML) services and the need for richer, validated catalogues of RI offerings.•The effort highlights the value of complementary tasks, activities and services across research infrastructures to contribute to societal health challenges. This present deliverable does not aim to provide a fully operational system but to lay the foundation for one. Sustained development, governance, and community engagement will be required to transform the prototype into a long-term, operational knowledge base for European PM.

Quality checklists have demonstrated benefits in healthcare and other high-reliability organizations, but there remains a gap in the understanding of design approaches and levels of stakeholder engagement in the development of these quality checklists. This scoping review aims to synthesize the current knowledge base regarding the use of various design approaches for developing quality checklists in healthcare. Secondary objectives are to explore theoretical frameworks, design principles, stakeholder involvement and engagement, and characteristics of the design methods used for developing quality checklists. The review followed the Preferred Reporting Items for Systematic Reviews 2020 checklist. Seven databases (PubMed, APA PsycInfo, CINAHL, Embase, Scopus, ACM Digital Library, and IEEE Xplore) were searched for studies using a comprehensive search strategy developed in collaboration with a health sciences librarian. Search terms included "checklist" and "user-centered design" and their related terms. The IAP2 Spectrum of Participation Framework was used to categorize studies by level of stakeholder engagement during data extraction. Twenty-nine studies met the inclusion criteria for this review. Twenty-three distinct design methods were identified that were predominantly non-collaborative in nature (e.g., interviews, surveys, and other methods that involved only one researcher and one participant at a given time). Analysis of the levels of stakeholder engagement revealed a gap in studies that empowered their stakeholders in the quality checklist design process. Highly effective, clear, and standardized methodologies are needed for the design of quality checklists. Future work needs to explore how stakeholders can be empowered in the design process, and how different levels of stakeholder engagement might impact implementation outcomes.

Understanding soybean responses to drought stress is critical for breeding drought-tolerant varieties. The extent of stomatal regulation of leaf water potential during drought stress can be characterized by the degree of isohydry. We hypothesize that abscisic acid (ABA) and hydraulic signals, two key factors influencing stomatal regulation, coordinate differently to regulate stomatal closure and impact yield performance under varying drought intensities in soybeans with different isohydric behaviors. To test this, we selected four landraces and four modern cultivars exhibiting diverse isohydric behaviors and conducted a progressive drought experiment. The experiment measured stomatal conductance, photosynthetic rate (P n ), and leaf hydraulic conductance (K leaf ) as soil moisture progressively declined. Additionally, a water control experiment assessed foliar ABA content, osmotic adjustment (OA), and yield components under moderate (50 % pot capacity) and severe stress (30 % pot capacity) drought stress were compared relative to well-watered conditions. Results showed that modern cultivars, characterized by more isohydric behavior, produced higher ABA levels, triggering earlier stomatal closure at higher soil water content, which was subsequently modulated by hydraulic signals during prolonged drought. Isohydric genotypes also displayed enhanced OA, enabling them to maintain high P n under severe drought stress. Under moderate drought stress, the isohydric cultivars experienced greater yield lose (21 % and 25 % for two isohydric cultivars vs. −8 % and 1 % for two landraces) and increased less water use efficiency for grain (WUEg). However, under severe drought stress, isohydric genotypes suffered less yield reduction (70 % and 72 % for isohydric cultivars vs. 79 % and 77 % for two anisohydric landraces) and increased more WUEg compared to anisohydric genotypes. Overall, isohydric genotypes, which exhibit a more conservative water-use strategy, are better suited for regions prone to severe drought stress. In contrast, anisohydric genotypes may perform better in regions with more reliable water availability. • Hydroscape area can represent the degree of isohydry in soybean. • Cultivars produce more ABA, enabling earlier stomatal closure to conserve water. • Cultivars enhanced osmatic adjustment to maintain higher photosynthesis under severe drought. • Modern soybean cultivars exhibit more isohydric traits with less yield reduction compared with landraces.

BACKGROUND: Several studies performed in the last years on the brain, showed that beta2-microglobulin (β2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble β2m have been implicated in cognitive impairments like that associated with chronic haemodialysis, or aortic valve replacement. Increased soluble β2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer's disease (AD). OBJECTIVE: To compare plasma β2m levels in healthy subjects and subjects with dementia or cognitive impairment. METHODS: We measured the concentration of β2m in a cohort of 245 individuals and compared sex matched, cognitive healthy individuals. RESULTS: We found higher levels of β2m in AD patients compared to non-AD MCI and healthy controls (2063 ng/mL ±852 versus 1613 ± 503 and 1832 ± 382 ng/mL, p< 0.001 and <0.033, respectively), while there was no difference between mild cognitive impairment (MCI) and healthy controls (p > 0.05). CONCLUSIONS: Our data confirm that β2m could play a role in AD. However, a replication study in an independent cohort would be necessary to confirm our preliminary results.

ABSTRACT Multi-omics approaches can offer powerful insights into personalized biomarker profiles relevant for disease diagnosis, prognosis, and therapeutics. However, separating meaningful biological variability from technical noise remains a major challenge. The EATRIS-Plus consortium analyzed blood samples from 127 healthy adults across six omics layers using twelve platforms, resulting in one of the most comprehensive multi-omics profiling datasets of healthy individuals available to date. We applied reproducible workflows to analyze and integrate these data, revealing several key findings. Sex significantly influenced all omics layers, emphasizing the importance of sex-balanced study designs. Age could be accurately predicted using epigenetic clocks, achieving high performance with our high-resolution enzymatic methylation sequencing data ( R 2 = 0.90), whereas candidate aging biomarkers were identified across all omics layers. The resulting dataset provides reference ranges in healthy individuals for abundance and variability of omics features, enabling robust power analyses, sample size estimations, and benchmarking of multi-omics integration methods. This resource can guide future biomarker discovery and personalized health research and was made FAIR-compliant and publicly available via the ClinData Portal ( https://clindata.imtm.cz ) and a Zenodo repository ( https://doi.org/10.5281/zenodo.17514796 ).

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs in 30% to 50% of patients undergoing cardiac surgery and is associated with increased morbidity and mortality. Prospective identification of structural/molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict risk of POAF may identify new molecular pathways and targets for prevention of this common morbid complication. METHODS: Right atrial appendage samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial (Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation), fixed in 10% buffered formalin, and embedded in paraffin for histology. We assessed general tissue morphology, cardiomyocyte diameters, myocytolysis (perinuclear myofibril loss), accumulation of perinuclear glycogen, interstitial fibrosis, and myocardial gap junction distribution. We also assayed NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT, CRP (C-reactive protein), and circulating oxidative stress biomarkers (F2-isoprostanes, F3-isoprostanes, isofurans) in plasma collected before, during, and 48 hours after surgery. POAF was defined as occurrence of postcardiac surgery atrial fibrillation or flutter of at least 30 seconds duration confirmed by rhythm strip or 12-lead ECG. The follow-up period for all arrhythmias was from surgery until hospital discharge or postoperative day 10. RESULTS: Thirty-five percent of patients experienced POAF. Compared with the non-POAF group, they were slightly older and more likely to have chronic obstructive pulmonary disease or heart failure. They also had a higher European System for Cardiac Operative Risk Evaluation and more often underwent valve surgery. No differences in left atrial size were observed between patients with POAF and patients without POAF. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen score or Cx43 distribution at the time of surgery was not significantly associated with incidence of POAF. None of these histopathologic abnormalities were correlated with levels of NT-proBNP, hs-cTnT, CRP, or oxidative stress biomarkers. CONCLUSIONS: In sinus rhythm patients undergoing cardiac surgery, histopathologic changes in the right atrial appendage do not predict POAF. They also do not correlate with biomarkers of cardiac function, inflammation, and oxidative stress. Graphic Abstract: A graphic abstract is available for this article.

BACKGROUND: Clinician well-being is crucial to the healthcare system, particularly during the COVID-19 pandemic, which intensified psychological distress among clinicians. This study examines well-being disparities between rural and urban clinicians using the NIOSH Worker Well-Being Questionnaire (WellBQ). METHODS: A cross-sectional survey was conducted with 222 clinicians from one urban and three rural hospitals in North Carolina between September and December 2022. The WellBQ assessed well-being across five domains. Data analysis identified concerning thresholds based on positive and negative responses, with discrepancies resolved through independent reviews and focus group validation. FINDINGS: In the work evaluation and experience domain, rural hospitals reported concerns with time paucity and work overload, while urban hospitals focused on work-related fatigue and job engagement. Rural hospitals noted issues with job benefits, health programs, and schedule flexibility, whereas urban hospitals emphasized the lack of supportive work culture and management trust. Both settings reported concerns in the physical environment and safety climate domain, including sexual harassment, physical violence, and bullying. Health status concerns in rural hospitals included overall stress and poor mental health, while urban hospitals highlighted chronic health conditions and risky drinking. CONCLUSION: This study identified significant well-being disparities between rural and urban clinicians, with urban hospitals showing higher concerning thresholds. Future research should refine these thresholds, explore workplace violence causes, and assess long-term impacts on clinician well-being.Applications to Practice:This study reveals significant well-being disparities between rural and urban clinicians, emphasizing the need for tailored occupational health interventions.

Research infrastructures (RIs) are facilities that enable the research community to use their specific technology platforms, resources, and services to conduct research and foster innovation. Europe’s RIs exist to solve systemic bottlenecks, pushing forward the frontiers of scientific disciplines, and enabling transformative technological development ranging from translational medicine to biobanking to clinical trials. In 2022, European wide RIs, including oncology experts and patient associations, came together to battle cancer by providing innovative cancer research services across Europe. CanSERV is a new EU-funded project under the Horizon Europe program that aims to provide a comprehensive portfolio of oncology-related research services to all scientists in EU member countries, associated countries and beyond. The CanSERV portfolio provides capabilities across the full breadth of cancer research and the translational pipeline, from basic biology research through to the delivery of late-phase clinical trials. Central to this project will be to facilitate cancer therapeutic developers with a set of robust, standardized, and validated assays for the development of novel Advanced Therapy Medicinal Products including cell and gene therapies, therapeutic vaccines, and RNA-based immunotherapies. Through this new initiative, the canSERV consortium will strive to meet the needs of academic and industry users from the EU and beyond to create a more effective, streamlined, and defragmented European oncology research infrastructure landscape.

Background: The aim of this study was to assess work system factors and nurse and physician well-being across professionals (nurse vs. physician) and geographic locations (rural vs. urban) during COVID-19 pandemic. Methods: This study invited nurses and physicians within four hospitals from one large healthcare system to participate: one urban academic medical center and three rural hospitals. We measured work systems factors using the National Academy of Medicine (NAM) framework and the National Institute for Occupational Safety and Health (NIOSH) survey. Wellbeing was measured using the 2-question summative burnout score, Patient Health Questionnaire (PHQ-9) to measure depression, and post-traumatic stress disorder (PTSD) checklist (PCL) to measure PTSD symptoms. Statistical analyses were conducted using Chi-square (for Likert-scale items) and t -tests (for continuous scales) as appropriate. Statistical significance was set at the .05 level, two-tailed. Results: Overall, our results suggested that nurses and physicians working in the urban settings experience more impeding work system factors and are more burned out, depressed, exhibit more PTSD symptoms, and face greater overall well-being issues, when compared to nurses and physicians working in the rural settings. Conclusions/Applications to Practice: This study examined a comprehensive set of work system factors and well-being measures to better understand differences between rural and urban settings, and nurses compared to physicians. By examining this entire set of measures, we were able to provide a greater insight into the key differences, highlighting opportunities for policy-level contributions to prevent work related impairments from reaching the healthcare workforce.

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Introduction: The classical functions of hepatic stellate cells (HSCs) are fat storage, vitamin A uptake and metabolism [1]. In response to cellular stress, HSCs transdifferentiate into myofibroblasts (MFB) and produce extracellular matrix proteins. Therefore, they have been implicated in the development if liver fibrosis and subsequent cirrhosis [2]. Recent investigations showed the antigen presentation capability of HSC [3–5]. Human and mice HSCs express genes typical for antigen- presenting cells (APC) including major histocompatibility complex (MHC) class II and the co-stimulatory molecules CD80 and CD86.

Background: Approximately 4000 preventable surgical errors occur per year in the US operating rooms, many due to suboptimal teamwork and safety behaviors. Such errors can result in temporary or permanent harm to patients, including physical injury, emotional distress, or even death, and can also adversely affect care providers, often referred to as the "second victim." Objective: Given the persistence of adverse events in the operating rooms, the objective of this study was to quantify the effect of an innovative and immersive virtual reality (VR)-based educational intervention on (1) safety behaviors of surgeons in the operating rooms and (2) sense-making regarding the overall training experience. Methods: This mixed methods pre- versus postintervention pilot study was conducted in a large academic medical center with 55 operating rooms. Safety behaviors were observed and quantified using validated Teamwork Evaluation of Non-Technical Skills instrument during surgical cases at baseline (101 observations; 83 surgeons) and postimmersive VR based intervention (postintervention: 24 observations within each group; intervention group [with VR training; 10 surgeons] and control [no VR training; 10 surgeons]). VR intervention included a 45-minute immersive VR-based training incorporating a pre- and postdebriefing based on Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) principles to improve safety behaviors. A 2-tailed, 2-sample t-test with adjustments for multiplicity of the tests was used to test for significance in observable safety behaviors between the groupings. The debriefing data underwent analysis through the phenomenological analysis method to gain insights into how participants interpreted the training. Results: Preintervention, all safety behaviors averaged slightly above "acceptable" scores, with an overall average of 2.2 (range 2-2.3; 0-3 scale). The 10 surgeons that underwent our intervention showed statistically significant (P<.05) improvements in 90% (18/20) of safety behaviors when compared to the 10 surgeons that did not receive the intervention (overall average 2.5, range 2.3-2.7 vs overall average 2.1, range 1.9-2.2). Our qualitative analysis based on 492 quotes from participants suggests that the observed behavioral changes are a result of an immersive experience and sense-making of key TeamSTEPPS training concepts. Conclusions: VR-based immersive training intervention focused on TeamSTEPPS principles seems effective in improving safety behaviors in the operating rooms as quantified via observations using the Teamwork Evaluation of Non-Technical Skills instrument. Further research with larger, more diverse sample sizes is needed to confirm the generalizability of these findings.

Abstract Background and Aims Resprouting plants are distributed across diverse global vegetation communities. In Caragana korshinkii, both the leaves and stems of resprouts exhibit reduced hydraulic conductivity and enhanced drought tolerance with increasing age following shoot removal. However, the way in which stomatal regulation responds to resprout age remains poorly understood. Methods This study was conducted in the field on 1- to 13-year-old resprouts of C. korshinskii. We focused on measuring three core parameters: leaf water potential (Ψleaf) at predawn and midday; stomatal conductance (gs) in the morning and midday; and stomatal sensitivity to Ψleaf. Additional measurements included leaf osmotic potential (Ψo), leaf turgor loss point (πtlp) and leaf dry mass per unit area (LMA). Key Results We found that as resprouts aged from 1 to 13 years, the predawn-to-midday Ψleaf difference (Ψpd − Ψmd) increased from 1.1 to 2.1 MPa; the morning-to-midday decline in stomatal conductance (Δgs morning–midday) decreased from 0.19 to 0.04 mol m−2 s−1; stomatal sensitivity to Ψleaf declined from 1.68 to 1.48; and water potential corresponding to a 50 % reduction in gs decreasing from −1.95 to −2.59 MPa. These shifts were correlated with more negative Ψo and πtlp and with increasing LMA. Conclusions This study reveals a transition from prioritizing drought avoidance to drought tolerance with resprout age in C. korshinskii following shoot removal. The adaptation highlights stomatal regulation as a key mechanism enhancing resprout drought resistance in arid shrub plantations.