This study synthesized the available evidence of simulation-based electronic health records (EHRs) training in educational and clinical environments for healthcare providers in the literature. The Arksey and O'Malley methodological framework was employed. A systematic search was carried out in relevant databases from inception to January 2020, identifying 24 studies for inclusion. Three themes emerged: (a) role of simulation-based EHR training in evaluating improvement interventions, (b) debriefing and feedback methods used, and (c) challenges of evaluating simulation-based EHR training. The majority of the studies aimed to emphasize the practical skills of individual medical trainees and employed post-simulation feedback as the feedback method. Future research should focus on (a) using simulation-based EHR training to achieve specific learning goals, (b) investigating aspects of clinical performance that are susceptible to skill decay, and (c) examining the influence of simulation-based EHR training on team dynamics.

This dataset provides the data extracted for the scoping review of the literature on preclinical models for personalised medicine, as part of the EU project on “Personalised Medicine Trials” (PERMIT). It covers the references for all articles selected as part of the scoping review of the two case models chosen, oncology and brain disorders.

Adopting rigorous standards is critical for ensuring interoperability, data integrity, and privacy as healthcare evolves from fragmented, non-digital workflows into integrated digital ecosystems. Globally, multiple countries have integrated these standards into their healthcare infrastructures, enhancing real-time data sharing, reducing errors, and enabling more efficient resource utilization. Implementing standards not only streamlines both clinical and administrative workflows but also fosters timely coordination among healthcare providers. Unified data architectures further pave the way for emerging technologies such as AI, IoT, and blockchain, allowing advanced analytics and continuous patient monitoring while safeguarding data. By creating an ecosystem in which information can seamlessly traverse multiple platforms, standards empower healthcare systems to evolve alongside cutting-edge innovations and ultimately improve care delivery. These integrated, adaptable solutions also support the development of equitable public health strategies and reinforce the pursuit of patient-centered, evidence-based care globally.

Background: Healthcare professionals in plastic and reconstructive surgery (PRS) face unique stressors that contribute to burnout, increasing the risk of errors and compromising patient care. Despite this, there is limited research on PRS burnout in the United States. This study aimed to measure burnout rates and identify high-impact improvement targets within a PRS division at a US academic medical center. Methods: A sequential mixed-methods study was conducted, involving systems analysis and contextual design methods. All surgeons (n = 5) and nonsurgeons (n = 9) were invited to participate (total n = 14). Burnout rates were measured, and workplace stressors were identified using surveys, focus groups, and contextual inquiries. High-impact, low-effort improvement targets were determined through impact-effort matrices. Results: Survey data from 13 respondents revealed an 85% burnout rate. Three focus groups and 14 contextual inquiries were conducted. After 13 participants validated and prioritized 2 affinity diagrams and provided 24 high-priority stressors, 8 respondents completed 2 surveys that yielded 6 high-impact/low-effort targets for organizational improvement efforts. Conclusions: This study highlights the high prevalence of burnout in PRS and identifies specific improvement targets for both surgeons and nonsurgeons. Findings suggest strategies such as improving respect and recognition for surgeons and streamlining clinic flow for nonsurgeons. Implementing these targeted improvements can enhance the well-being of healthcare professionals and ultimately improve patient care. The study's methods can be replicated by other healthcare organizations to identify and address burnout-related issues effectively.

Background: Neurodegeneration plays a major role in determining disability in multiple sclerosis (MS) patients. Hence, there is increasing need to identify reliable biomarkers, which could serve as prognostic measure of disease progression. Objectives: To assess whether cerebrospinal fluid (CSF) tau and β-amyloid (Aβ) levels were altered in newly diagnosed MS patients and correlated with disability. Moreover, we investigated whether these CSF biomarkers associate with macroscopic brain tissue damage measures. Methods: CSF Aβ and tau levels were determined by enzyme-linked immunosorbent assay in CSF samples from 48 newly diagnosed MS patients, followed-up clinically for 3 years by recording their Expanded Disability Status Scale score at 6-month intervals, and 45 controls. All patients underwent magnetic resonance imaging at baseline and at the end of follow-up to quantify their lesion load (LL). Results: CSF Aβ levels were significantly reduced in patients compared to controls ( p < 0.001). Lower CSF Aβ levels at baseline were a disability predictor at 3-year follow-up ( p = 0.009). CSF tau levels correlated with T2- and T1-LL ( p < 0.001). Conclusion: CSF Aβ reduction is a promising biomarker of neurodegeneration and may predict patients’ clinical outcome. Therefore, CSF Aβ should be considered as a potential biomarker of prognostic value.

The well-being of medical physicists can impact overall system performance, patient safety, and quality of patient care. There are limited formal assessments of factors contributing to physicists well-being. Nine medical physicists at a US academic medical center were surveyed on 21 workplace factors, drawn from the National Academy of Medicine's systems model of clinician burnout and professional well-being between May 2022 and August 2022. Highly rated factors were summarized and presented to medical physicists in focus groups. Contextual inquiries (a form of shadowing) were conducted to gather additional information about factors contributing to well-being. Qualitative data from the survey, focus groups, and contextual inquiries were used to generate an affinity model, which medical physicists then validated and used to prioritize top factors. Twenty-two medical physicists at the academic medical center and three other US academic medical centers rated these factors by level of impact and level of effort, and improvement recommendations were made based on these results. Key factors affecting medical physicist well-being included inadequate staffing, work-life integration, excessive workload, and time pressure. Twenty-two medical physicists across four institutions prioritized the following top factors for improvement: (i) retain the hybrid work model, (ii) hire additional medical physicists to cover clinic responsibilities, (iii) limit or compensate after hours work, (iv) improve scheduling workflows, and (v) improve communication and visibility from organization-level leadership and administration. High impact, low effort priorities to improve medical physicist well-being across the four institutions include work-life integration, scheduling workflows, and relationships with leadership. These factors seem to be within the improvement control of each radiation oncology center. Further research is needed to establish the generalizability of our findings and spearhead broad policy changes.

Recently, synthesis and secretion of connective tissue growth factor (CTGF)/CYR61/CTGF/NOV-family member 2 (CCN2) in cultures of hepatocytes were shown, which are sensitively up-regulated by exogenous TGF-beta. In this study TGF-beta-dependent CTGF/CCN2 expression in hepatocytes cultured under completely TGF-beta-free conditions was analysed by Western-blots, metabolic labelling, and CTGF-reporter gene assays. In alkaline phosphatase monoclonal anti-alkaline phosphatase complex (APAAP)-staining of cultured hepatocytes it was demonstrated that latent TGF-beta within the hepatocytes becomes rapidly detectable during culture indicating an intracellular demasking of the mature TGF-beta antigen. Subsequent signaling to theCTGF/CCN2 promoter occurs via p-Smad2, whereas p-Smad3 does not seem to be involved. Cycloheximide did not abolish the rapid immunocytochemical appearance of mature TGF-beta, but calpain inhibitors partially suppressed intracellular TGF-beta activation and subsequently CTGF up-regulation. Calpain treatment had the reverse effect. None of the inhibitors of extracellular TGF-beta signalling was effective in the reduction of spontaneous CTGF synthesis, but intracellularly acting Alk 4-/Alk 5-specific inhibitor SB-431542 was able to diminish CTGF expression. The assumption that latent intracellular TGF-beta is activated by calpains during culture-induced stress or injurious conditions in the liver in vivo was further validated by a direct effect of calpains on the activation of recombinant latent TGF-beta. In conclusion, these data are the first to suggest the possibility of intracrine TGF-beta signalling due to calpain-dependent intracellular proteolytic activation leading to transcriptional activation of CTGF/CCN2 as a TGF-beta-sensitive reporter gene. This mechanism might be deleterious for keeping long-term hepatocyte cultures due to TGF-beta-induced apoptosis and, further, might be of relevance for induction of apoptosis or epithelial-mesenchymal transition of hepatocytes in injured liver.

Summary: Large national, integrated biobanks have revolutionized how genetics-linked healthcare data can be scaled, providing access to massive databases to researchers globally. Recognizing the importance of integrated biobanks for public health and national scientific advancement, countries around the world have launched similar initiatives. Despite comprising a quarter of the world’s population, South Asia accounts for only 1·8% of EHR-indexed publications and 0·2% of GWAS participants. We argue for a South Asia Biobank Consortium: (1) a regional governing body overseeing interoperability across (2) national-level integrated biobanks that adapts the UK Biobank model to regional contexts (3) supported by federated analytics infrastructure with global access. If enacted, the consortium represents a scientific imperative and a pathway to digital health equity for nearly two billion people living in South Asia. We present a framework based on hallmarks of successful integrated biobanks and critical success factors. We propose a timeline for its establishment. Without decisive action, current disparities will worsen, leaving South Asia’s population marginalized as the transformative revolution continues. With a federated, equitable strategy, South Asia can transform from a peripheral participant into a central driver of biomedical discovery – strengthening health systems, advancing equity, and realizing the global promise of precision medicine.

An effective response to the coronavirus disease 2019 (COVID-19) pandemic requires a better understanding of the biology of the infection and the identification of validated biomarker profiles that would increase the availability, accuracy, and speed of COVID-19 testing. Here, we describe the strategic objectives and action lines of the European Alliance of Medical Research Infrastructures (AMRI), established to improve the research process and tackle challenges related to diagnostic tests and biomarker development. Recommendations include: the creation of a European taskforce for validation of novel diagnostic products, the definition and promotion of criteria for COVID-19 samples biobanking, the identification and validation of biomarkers as clinical endpoints for clinical trials, and the definition of immune biomarker signatures at different stages of the disease. An effective management of the COVID-19 pandemic is possible only if there is a high level of knowledge and coordination between the public and private sectors within a robust quality framework.

Background/Aims YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. Methods The CHI3L1 −131G → C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n = 440) by 5′-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 −131G → C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. Results CHI3L1 −131G → C genotype was strongly associated with the stage of liver fibrosis in the screening (n = 265, P = 0.001) and validation cohort (n = 175, P = 0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P = 0.002). Conclusions The CHI3L1 promoter polymorphism −131G → C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker. YKL-40 is a chitinase-like protein involved in matrix remodelling and a non-invasive fibrosis marker. We assessed whether a functional promoter polymorphism in CHI3L1, encoding YKL-40, is associated with HCV-induced liver fibrosis and influences YKL-40 serum concentrations. The CHI3L1 −131G → C promoter polymorphism was genotyped in two cohorts of HCV infected patients (n = 440) by 5′-endonuclease assays. Histological fibrosis scores and YKL-40 serum levels (ELISA) were associated with CHI3L1 −131G → C by quantitative and qualitative genetic analyses and corrected by multivariate analysis. CHI3L1 −131G → C genotype was strongly associated with the stage of liver fibrosis in the screening (n = 265, P = 0.001) and validation cohort (n = 175, P = 0.009). Homozygous carriers of the G allele were protected from severe fibrosis (F3/F4). This association was confirmed after correction for age and gender. Functionally, the G allele was associated with reduced serum levels of YKL-40 in HCV infected patients (P = 0.002). The CHI3L1 promoter polymorphism −131G → C determines YKL-40 serum levels and is associated with the severity of HCV-induced liver fibrosis. These results suggest a functional role of YKL-40 in liver fibrogenesis and should be taken into account when using YKL-40 as a non-invasive fibrosis marker.

This is the protocol for a series of scoping reviews that will map the general concept of methods for personalised medicine, to set the basis for the discussion on robustness and reproducibility of personalised medicine development programmes. The final goal is the identification of standards and needs in terms of methodology of data generation, management, analysis and interpretation to improve clinical studies in personalised medicine. For the purpose of this review, four main aspects of the general concept of personalised medicine will be analysed: Methods for stratification and validation cohorts Methods for machine learning applied to stratification Pre-clinical methods for translational development of treatment options and treatments selection Methods for clinical trials in personalised medicine

We describe a system that permits conditional mobilization of a Sleeping Beauty (SB) transposase allele by Cre recombinase to induce cancer specifically in a tissue of interest. To demonstrate its potential for developing tissue-specific models of cancer in mice, we limit SB transposition to the liver by placing Cre expression under the control of an albumin enhancer/promoter sequence and screen for hepatocellular carcinoma (HCC)-associated genes. From 8,060 nonredundant insertions cloned from 68 tumor nodules and comparative analysis with data from human HCC samples, we identify 19 loci strongly implicated in causing HCC. These encode genes, such as EGFR and MET, previously associated with HCC and others, such as UBE2H, that are potential new targets for treating this neoplasm. Our system, which could be modified to drive transposon-based insertional mutagenesis wherever tissue-specific Cre expression is possible, promises to enhance understanding of cancer genomes and identify new targets for therapeutic development.

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.