Swiss School of Archaeology in Greece
UNIL IRIS | Institutional Research Information SystemNot a member yet
170689 research outputs found
Sort by
Topical Ruxolitinib and Delgocitinib Versus Systemic JAK Inhibitors: A Comparative Safety Review
No full textJanus Kinase Inhibitors (JAKi) represent a novel class of drugs for the treatment of chronic inflammatory skin diseases. Topical JAKi (t-JAKi) offer targeted therapy at potentially reduced systemic side effects and improved long-term safety compared to systemic JAKi (s-JAKi). This narrative review assesses the pharmacokinetics and safety profile of currently available t-JAKi, ruxolitinib and delgocitinib, with a comparative analysis to s-JAKi. Pharmacokinetic data show that topical ruxolitinib achieves effective dermal concentrations, with minimal systemic exposure. Clinical trials consistently report low rates of adverse events, primarily application-site reactions, while systemic events such as upper respiratory tract infections occur at rates comparable to placebo. Data on delgocitinib similarly indicate negligible systemic absorption and a favorable safety profile. Taken together, these findings suggest that t-JAKi may represent safer alternatives to s-JAKi for selected patients with localized inflammatory skin diseases, particularly those with comorbidities or heightened systemic risk. Long-term studies and real-world evidence are needed to confirm sustained safety and guide their optimal integration into clinical practice
Expert review of CLABSI prevention in the NICU: supporting the transition of investigational drugs into clinical practice.
No full textCentral venous catheters (CVCs) are essential for administering life-saving medications, parenteral nutrition, and fluids in extremely premature (EP; i.e., 28 weeks' gestational age) infants. Indeed, CVCs have enabled increased survival and improved outcomes in EP infants over the last several decades. However, CVCs remain a major risk factor for central line-associated bloodstream infection (CLABSI), which can lead to serious complications in this vulnerable population. While many neonatal intensive care units (NICUs) have adopted CVC bundles to reduce CLABSI risk, implementation remains inconsistent, contributing to significant variability across centers. A minimized and reproducible baseline rate of CLABSI is important not only to physicians caring for EP infants and their families but also to clinical investigators and regulatory authorities in the evaluation of experimental therapies aimed at combating the complications of prematurity, such as bronchopulmonary dysplasia, retinopathy of prematurity, and impaired neurological development. CLABSIs may confound clinical outcomes and thus impact the interpretation of trial results. We propose a standardized central line bundle, informed by current clinical practice and a critical appraisal of the literature, for mandatory use in clinical trials.
Consistent application of a standardized central line bundle would reduce variability in baseline CLABSI rates across study sites, enabling more accurate benefit-risk assessments of experimental therapies, particularly those requiring central venous access, in this population of infants with a high unmet medical need.
• Central venous catheters (CVCs) are essential for administering life-saving treatments in extremely premature infants, significantly improving their survival and outcomes. CVCs, however, are known to increase the risk of central line-associated bloodstream infection (CLABSI). • Central line bundles are routinely implemented in clinical practice with demonstrable benefit in reducing CLABSI. Still, their impact often wanes as the focus and stringency on bundle components and audit programs decrease.
• We propose a standardized central line bundle for mandatory use in clinical trials. This will help reduce variability in baseline CLABSI rates across study centers, enabling a more accurate evaluation of the benefit-risk profile of experimental therapies-especially those requiring administration via central venous catheters
Intramyocardial fatty infiltration lesion in sporadic inclusion body myositis: a case report.
No full textSporadic inclusion body myositis (sIBM), the most common inflammatory muscle disorder in adults over 50 years, is often misdiagnosed due to its gradual onset and its common but unspecific muscle weakness in older adults. Diagnosis relies on clinical, radiological, and pathological features. Cardiac involvement is rare, prompting this case description and a comprehensive literature analysis. A 73-year-old woman diagnosed with sIBM in 2021 through muscle biopsy had been experiencing muscular symptoms since 2015. Her condition progressively worsened, affecting daily activities. Annual follow-ups revealed a moderate obstructive syndrome on respiratory testing, prompting a cardiac evaluation. Cardiac magnetic resonance (CMR) imaging identified intramyocardial lesions consistent with fatty infiltration, highlighting the interest of advanced imaging in sIBM management. Cardiac involvement in sIBM is presumed rare compared to other idiopathic inflammatory myopathies, though the exact frequency remains unclear. Early identification of heart alterations by CMR in sIBM can be prognostically valuable, guiding follow-up and interventions. However, literature on this subject is limited to small cohort studies and case reports describing complications. Given the slow progression of sIBM and the limited efficacy of current treatments, the discovery of myocardial lesions could warrant closer cardiological monitoring. Larger cohort studies are needed to explore potential new therapeutic approaches. Our case underscores the importance of CMR in detecting subtle cardiac manifestations in sIBM and illustrates the potential prognostic value of cardiac assessment in the management of sIBM
Deep Learning for fODF Estimation in Infant Brains: Model Comparison, Ground-Truth Impact, and Domain Shift Mitigation
No full textThe accurate estimation of fiber orientation distribution functions (fODFs) in diffusion magnetic resonance imaging (MRI) is crucial for understanding early brain development and its potential disruptions. Although supervised deep learning (DL) models have shown promise in fODF estimation from neonatal diffusion MRI (dMRI) data, the out-of-domain (OOD) performance of these models remains largely unexplored, especially under diverse domain shift scenarios. This study evaluated the robustness of three state-of-the-art DL architectures: multilayer perceptron (MLP), transformer, and U-Net/convolutional neural network (CNN) on fODF predictions derived from dMRI data. Using 488 subjects from the developing Human Connectome Project (dHCP) and the Baby Connectome Project (BCP) datasets, we reconstructed reference fODFs from the full dMRI series using single-shell three-tissue constrained spherical deconvolution (SS3T-CSD) and multi-shell multi-tissue CSD (MSMT-CSD) to generate reference fODF reconstructions for model training, and systematically assessed the impact of age, scanner/protocol differences, and input dimensionality on model performance. Our findings reveal that U-Net consistently outperformed other models when fewer diffusion gradient directions were used, particularly with the SS3T-CSD-derived ground truth, which showed superior performance in capturing crossing fibers. However, as the number of input diffusion gradient directions increased, MLP and the transformer-based model exhibited steady gains in accuracy. Nevertheless, performance nearly plateaued from 28 to 45 input directions in all models. Age-related domain shifts showed asymmetric patterns, being less pronounced in late developmental stages (late neonates, and babies), with SS3T-CSD demonstrating greater robustness to variability compared to MSMT-CSD. To address inter-site domain shifts, we implemented two adaptation strategies: the Method of Moments (MoM) and fine-tuning. Both strategies achieved significant improvements ( p < 0.05 ) in over 95% of tested configurations, with fine-tuning consistently yielding superior results and U-Net benefiting the most from increased target subjects. This study represents the first systematic evaluation of OOD settings in DL applications to fODF estimation, providing critical insights into model robustness and adaptation strategies for diverse clinical and research applications.
© 2025 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC
From global to local: rethinking the design of probiotic intervention strategies
No full textThe human microbiome plays a crucial role in maintaining homeostasis and influencing disease development, yet its composition varies across geography, age, and lifestyle. These differences challenge the efficacy of universal probiotic treatments and call for more personalized or regionally adapted approaches. In this review we examine the limitations of universal probiotics, emphasizing the importance of considering host-microbe co-adaptation, local dietary practices, and ecological context. We argue that probiotic design must account for microbial diversity, strain-level adaptation, and functional redundancy, and we explore how these factors affect colonization success and therapeutic potential. Finally, we discuss ways to re-center microbiome knowledge within diverse ecological, cultural, and epistemic traditions for a global, inclusive approach allowing for microbiome-targeted therapies that are both effective and accessible.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved
Identification of individuals at high risk of developing rheumatoid arthritis: a balanced random forest model in a cohort of 1544 first-degree relatives
No full textTo identify in a genetically susceptible population individuals at higher risk of developing rheumatoid arthritis (RA) using a classification approach combining known epidemiological risk factors, serological biomarkers, genetics, clinical signs and symptoms.
We used data from the prospective SCREEN-RA (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) cohort of 1540 first-degree relatives of RA patients (RA-FDRs). The primary outcome was the development of RA. Additionally, we used seropositive inflammatory arthritis (IA) as a secondary outcome for exploratory analyses. Balanced random forest (BRF) models were fit and evaluated through fivefold cross-validation to avoid overfitting. We chose a classification threshold that targeted high sensitivity.
After a mean follow-up of 7.1 years, 27 participants developed RA and 126 developed seropositive IA. The BRF demonstrated moderate predictive performance, characterised by high sensitivity (≥0.85) but modest specificity. Rheumatoid factors (RFs) had the highest importance in RA prediction, followed by symptoms of 'clinically suspected arthralgia' (CSA) scale. Age, gender and anti-RA33 autoantibodies were the main variables for the prediction of seropositive IA.
Overall, the results demonstrate that predicting RA by combining genetics, serological biomarkers, epidemiological risk factors and clinical signs is promising, although model generalisation remains challenging. The low prevalence of RA in the cohort complicates the development of highly accurate prediction models. Future efforts should focus on including external validation and potentially incorporating additional biomarkers to enhance the sensitivity and overall performance of the predictive tests.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group
Influence of scleral thickness on photodynamic therapy outcomes in central serous chorioretinopathy.
No full textTo test the prognostic role of anterior scleral substantia propria (ASSP) thickness in predicting the 3-month response after half-dose photodynamic therapy (PDT) in central serous chorioretinopathy (CSCR) and to assess its clinical relevance of ASSP in different CSCR phenotypes.
A prospective, exploratory, multi-centre cohort study conducted at IRCCS San Martino Hospital (Genoa, Italy) and Jules-Gonin Eye Hospital (Lausanne, Switzerland). Demographic and clinical data, and optical coherence tomography (OCT) were collected at baseline and 3 months after PDT. Based on OCT images, we categorized CSCR phenotypes and collected clinically relevant imaging metrics. ASSP thickness was obtained from four different measurements using anterior segment (AS) OCT. Multivariable regression models were performed to evaluate the distribution of ASSP thicknesses among different CSCR phenotypes and to test the prognostic role of ASSP thickness in discriminating between PDT responders (complete subretinal fluid reabsorption) and partial responders.
The study cohort comprised 109 Caucasian patients (82 males, 75.2%) with a total of 142 eyes: 84 eyes simple (59.1%) versus 58 eyes complex (40.9%) CSCR. A linear normal model confirmed a positive association between complex CSCR and higher ASSP thickness (β = 26.1, 95% CL = 12.1/40.1, p < 0.001), with a low prevalence of ciliochoroidal effusion loculations in AS-OCT (1/142 eyes, 0.7%). ASSP thickening was positively linked to the presence of posterior cystoid retinal degeneration (PCRD; p = 0.002), indicating a potential role in the pathogenesis of severe CSCR phenotypes. In the subgroup of treated patients (61 eyes), 63.9% had a complete response after PDT. In these patients a logistic binary model highlighted a significantly higher risk of PDT non-responsiveness (OR = 9.62, 95% CL = 2.44/37.9, p = 0.001) associated with a 60-unit increase in ASSP thickness levels. By contrast, other anatomical parameters (i.e., body surface area, age, gender, axial length) showed no remarkable prognostic roles.
This research highlighted the association of ASSP thickening with complex CSCR phenotype in Caucasian patients and its role in predicting PDT efficacy. These findings enhance our comprehension of the anatomical risk factors in patients affected with CSCR and potentially guide a better understanding of non-responsive cases to PDT treatment
Grammaire française du vivre-ensemble
No full textQu’est-ce que le vivre-ensemble et quel rapport avec la langue ?
Dans la conversation, le vivre-ensemble, c’est respecter l’autre, lui faire une place et parler de soi. Parler, c’est tenir un subtil équilibre entre ces trois dimensions, explorées ici en 123 manières de parler le français, décrites simplement et exemplifiées
Navigating the design of simulated exercising peers: insights from a participatory design study
No full textBackground
To fight sedentary lifestyles, researchers have introduced various technological interventions aimed at promoting physical activity through social support. These interventions encourage people to exercise together, maintaining high levels of motivation. However, the unpredictable nature of human peers makes it challenging to control behavior and balance these interventions effectively. Artificial intelligence agents, on the other hand, can provide consistent social support and are more controllable. Hence, we propose Simulated Exercising Peers (SEPs) as a promising solution for providing agent-based social support for physical activity.
Method
Participatory design sessions were conducted, involving young adults in the creation of SEP-based interventions. Sixteen participants generated four prototypes that varied in aesthetics, behavior, and communication style, with outcomes analyzed through the lens of Self-Determination Theory to better understand the motivational implications of each design.
Results
Findings highlight key components crucial for designing SEPs that enhance acceptance and efficiently integrate into physical activity interventions. Additionally, the study revealed how the aesthetics and behavior of SEPs could potentially deceive users, which can lead to user disengagement from interventions involving SEPs. Participants also defined two distinct social roles for the SEPs, i.e., coach, and companion, each associated with unique communication styles.
Conclusion
This study offers five design guidelines for the development of SEPs, AI agents aimed at promoting physical activity through social support, and highlights opportunities for their integration into broader physical activity interventions
