Swiss School of Archaeology in Greece
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A review of the Quichua Porcupine <i>Coendou quichua</i> complex (Rodentia: Erethizontidae) with the description of a new species from Colombia
No full textStress CMR Perfusion Imaging in the Medicare-Eligible Population: Insights From the SPINS Study.
No full textPatients aged ≥65 years account for a disproportionately large portion of cardiovascular (CV) events and pose a challenge for noninvasive detection of coronary artery disease.
This study sought to determine the prognostic value of stress cardiac magnetic resonance (CMR) in a Medicare-eligible group of patients in a multicenter setting in the United States.
From a multicenter U.S. registry, the study identified patients aged ≥65 years who were referred for stress CMR for evaluation of myocardial inducible ischemia. The primary outcome was defined as CV death or nonfatal myocardial infarction, whereas the secondary outcome was defined as any primary outcome, hospitalization for unstable angina, hospitalization for congestive heart failure, and unplanned late coronary artery bypass grafting. The associations of CMR findings with CV outcomes adjusted to clinical risk markers and health care cost spending were determined.
Among 1,780 patients (aged 73 ± 5.7 years; 46% female), study investigators observed 144 primary events and 323 secondary events, over a median follow-up of 4.8 years. The presence of inducible ischemia and late gadolinium enhancement (LGE) was associated with incrementally higher event rates. Patients with neither inducible ischemia nor LGE experienced a <1% annualized rate of primary outcome. In a multivariable model adjusted for CV risk factors, inducible ischemia and LGE maintained an independent association with primary (HR: 2.80 [95% CI: 1.93-4.05]; P < 0.001; and HR: 1.85 [95% CI: 1.21-2.82]; P = 0.004, respectively) and secondary (HR: 2.46 [95% CI: 1.90-3.19]; P < 0.001; and HR: 1.72 [95% CI: 1.30-2.27]; P < 0.001, respectively) outcomes. Rates of revascularization, as well as downstream costs for patients without CMR-detected inducible ischemia, remained low throughout the follow-up period.
In a multicenter cohort of Medicare-eligible older patients, stress CMR was effective in providing risk stratification. (Stress CMR Perfusion Imaging in the United States [SPINS] study; NCT03192891)
Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody.
No full textAfrican trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth
A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.
No full textEvaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.
A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up. Seventy cases were reviewed by 42 pulmonary pathologists first according to the WHO classification and after tutorial according to a modified classification. A third round was conducted based on feedback from 41 peers of previous rounds. Additionally, orthogonal biomarker analysis was performed.
In the first two rounds, 42 pathologists from 13 countries assessed all 70 cases, while 36 pathologists evaluated 41 non-unanimous cases in the third round. Kappa values for invasiveness increased in rounds 1, 2, and 3 to 0.27, 0.45 and 0.62, respectively. In contrast to low variation in total tumor size measurements (6 %), a marked increase in invasive tumor size variation was observed (42 %), which was associated with high uncertainty. In the third round 10 cases were non-invasive, all without recurrence. The modified classification showed in the 3rd round marked reduction of the variation in pT staging compared to the current WHO classification. Proliferation rate, tumor mutational burden, and transcriptomic profiles supported the distinction between invasive cases and non-invasive cases of the modified classification.
The modified classification demonstrates essentially higher reproducibility compared to the current WHO classification in NMA. The modified classification proves valuable in identifying low-risk lesions that are entirely non-invasive, and is supported by biomarker analysis
The hit-and-run of cell wall synthesis: LpoB transiently binds and activates PBP1b through a conserved allosteric switch
No full textThe peptidoglycan (PG) cell wall is the primary protective layer of bacteria, making the process of PG synthesis a key antibiotic target. Class A penicillin-binding proteins (aPBPs) are a family of conserved and ubiquitous PG synthases that fortify and repair the PG matrix. In gram-negative bacteria, these enzymes are regulated by outer-membrane tethered lipoproteins. However, the molecular mechanism by which lipoproteins coordinate the spatial recruitment and enzymatic activation of aPBPs remains unclear. Here we use single-molecule FRET and single-particle tracking in E. coli to show that a prototypical lipoprotein activator LpoB triggers site-specific PG synthesis by PBP1b through conformational rearrangements. Once synthesis is initiated, LpoB affinity for PBP1b dramatically decreases and it dissociates from the synthesizing enzyme. Our results suggest that transient allosteric coupling between PBP1b and LpoB directs PG synthesis to areas of low peptidoglycan density, while simultaneously facilitating efficient lipoprotein redistribution to other sites in need of fortification.
© 2025. The Author(s)
Live screening of transgenic zebrafish using AI-assisted image analysis identifies ursonic acid as a Tfeb activator for muscle health and aging
No full text"Appelé à être abandonné". La place des spectateurs dans les créations et théories de Romeo Castellucci.
No full textCurrent practice positions on oesophageal biopsy sampling and endoscopic dilation in adult patients with eosinophilic oesophagitis
No full textBackground
There is a gap of knowledge with regards to the optimal biopsy sampling procedure as well as the technical and temporal aspects of endoscopic dilation for eosinophilic oesophagitis (EoE). Current guidelines lack specific recommendations.
Methods
The Swiss Network for Eosinophilic Gastrointestinal Diseases, together with members from The International Gastrointestinal Eosinophil Researchers, assembled a topical review consensus group. After a systematic literature review, two rounds of voting in a Delphi-style process were performed. Statements were rated on an even Likert scale ranging from 1 (strong disagreement) to 4 (strong agreement). Statements were accepted if they achieved an agreement of >80%.
Results
The experts agreed on a total of 10 statements, 5 statements about biopsy sampling and 5 statements about endoscopic dilation. There was agreement about the need for separately collecting biopsies from at least two segments of the oesophagus, standardised endoscopic and histological disease assessment and the optimal biopsy technique (one biopsy per attempt using the turn and suction technique). The experts further agreed on the early use of endoscopic dilation whenever fibrostenosis is present and an interval of 6–12 months between dilations in most cases. In the absence of fibrostenosis and dysphagia symptoms, empiric dilation for non-dysphagia symptoms cannot be recommended.
Conclusion
These current practice positions summarise the recommended approach to oesophageal biopsy sampling and endoscopic dilation in adult patients with EoE. Given the lack of randomised controlled data, the statements made in this topical review consensus are largely based on expert opinion and should be seen as guidance in clinical practice that will evolve in the future as newer data emerge
PSMA PET in renal cell carcinoma: an update and future aspects
No full textProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising molecular imaging tool for renal cell carcinoma (RCC), particularly for the clear-cell subtype (ccRCC). Unlike its expression in prostate cancer, PSMA in ccRCC is localised mainly to the endothelial cells of tumour-associated neovasculature, where it reflects angiogenic activity driven by the VHL-HIF-VEGF axis. This biological substrate provides the rationale for using PSMA-targeted imaging as a surrogate of angiogenesis and as a potential predictive biomarker in systemic therapy. Evidence from retrospective and prospective studies demonstrates high diagnostic accuracy of PSMA PET/CT in ccRCC, with detection rates exceeding 80-90%, outperforming conventional imaging and [¹⁸F]FDG PET/CT, particularly in metastatic disease. Quantitative PET-derived parameters, including SUVmax and heterogeneity indices, have shown correlation with VEGFR-2, PDGFR-β, and HIF-2α expression and may serve as predictors of response to tyrosine kinase inhibitors and immunotherapy combinations. PSMA-guided metastasis-directed therapy has also shown encouraging control rates in oligometastatic settings. Beyond its diagnostic role, PSMA PET offers a foundation for theragnostic applications. Early clinical experience with [¹⁷⁷Lu]Lu-PSMA radioligands and ongoing trials such as RENALUT and PRadR are exploring the feasibility of radioligand therapy targeting PSMA-positive ccRCC neovasculature. Although biological and kinetic barriers persist, PSMA-based imaging and therapy represent a feasible, rapidly translatable platform that bridges diagnosis and targeted treatment, marking a pivotal step towards personalised, imaging-guided management of advanced ccRCC.
Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved