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| 2. |
- Korenblik, R., et al.
(författare)
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Dragon 1 Protocol Manuscript : Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy
- 2022
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Ingår i: Cardiovascular and Interventional Radiology. - : Springer. - 0174-1551 .- 1432-086X. ; 45, s. 1391-1398
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Tidskriftsartikel (refereegranskat)abstract
- Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.
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| 3. |
- Ricci, M., et al.
(författare)
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The XXL Survey: XLIV. Sunyaev-Zel'dovich mapping of a low-mass cluster at z ∼1: A multi-wavelength approach
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
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Tidskriftsartikel (refereegranskat)abstract
- High-mass clusters at low redshifts have been intensively studied at various wavelengths. However, while more distant objects at lower masses constitute the bulk population of future surveys, their physical state remain poorly explored to date. In this paper, we present resolved observations of the Sunyaev-Zel'dovich (SZ) effect, obtained with the NIKA2 camera, towards the cluster of galaxies XLSSC 102, a relatively low-mass system (M500 ∼ 2 × 1014 M·) at z = 0.97 detected from the XXL survey. We combine NIKA2 SZ data, XMM-Newton X-ray data, and Megacam optical data to explore, respectively, the spatial distribution of the gas electron pressure, the gas density, and the galaxies themselves. We find significant offsets between the X-ray peak, the SZ peak, the brightest cluster galaxy, and the peak of galaxy density. Additionally, the galaxy distribution and the gas present elongated morphologies. This is interpreted as the sign of a recent major merging event, which induced a local boost of the gas pressure towards the north of XLSSC 102 and stripped the gas out of the galaxy group. The NIKA2 data are also combined with XXL data to construct the thermodynamic profiles of XLSSC 102, obtaining relatively tight constraints up to about ∼r500, and revealing properties that are typical of disturbed systems. We also explore the impact of the cluster centre definition and the implication of local pressure substructure on the recovered profiles. Finally, we derive the global properties of XLSSC 102 and compare them to those of high-mass-and-low-redshift systems, finding no strong evidence for non-standard evolution. We also use scaling relations to obtain alternative mass estimates from our profiles. The variation between these different mass estimates reflects the difficulty to accurately measure the mass of low-mass clusters at z ∼ 1, especially with low signal-to-noise ratio data and for a disturbed system. However, it also highlights the strength of resolved SZ observations alone and in combination with survey-like X-ray data. This is promising for the study of high redshift clusters from the combination of eROSITA and high resolution SZ instruments and will complement the new generation of optical surveys from facilities such as LSST and Euclid.
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| 4. |
- Adam, R. M., et al.
(författare)
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The XXL Survey: LI. Pressure profile and Y SZ -M scaling relation in three low-mass galaxy clusters at z∼1 observed with NIKA2
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Tidskriftsartikel (refereegranskat)abstract
- Context. The thermodynamical properties of the intracluster medium (ICM) are driven by scale-free gravitational collapse, but they also reflect the rich astrophysical processes at play in galaxy clusters. At low masses (∼1014M) and high redshift (z≳1), these properties remain poorly constrained, observationally speaking, due to the difficulty in obtaining resolved and sensitive data. Aims. We aim to investigate the inner structure of the ICM as seen through the Sunyaev-Zel’dovich (SZ) effect in this regime of mass and redshift. We focused on the thermal pressure profile and the scaling relation between SZ flux and mass, namely the YSZ-M scaling relation. Methods. The three galaxy clusters XLSSC 072 (z=1.002), XLSSC 100 (z=0.915), and XLSSC 102 (z=0.969), with M500∼2×1014M, were selected from the XXL X-ray survey and observed with the NIKA2 millimeter camera to image their SZ signal. XMM-Newton X-ray data were used as a complement to the NIKA2 data to derive masses based on the YX-M relation and the hydrostatic equilibrium. Results. The SZ images of the three clusters, along with the X-ray and optical data, indicate dynamical activity related to merging events. The pressure profile is consistent with that expected for morphologically disturbed systems, with a relatively flat core and a shallow outer slope. Despite significant disturbances in the ICM, the three high-redshift low-mass clusters follow the YSZ-M relation expected from standard evolution remarkably well. Conclusions. These results indicate that the dominant physics that drives cluster evolution is already in place by z∼1, at least for systems with masses above M500∼1014M.
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| 6. |
- Amorín, R. O., et al.
(författare)
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Ubiquitous broad-line emission and the relation between ionized gas outflows and Lyman continuum escape in Green Pea galaxies
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- We report observational evidence of highly turbulent ionized gas kinematics in a sample of 20 Lyman continuum (LyC) emitters (LCEs) at low redshift (z ∼ 0.3). Detailed Gaussian modeling of optical emission line profiles in high-dispersion spectra consistently shows that both bright recombination and collisionally excited lines can be fitted as one or two narrow components with intrinsic velocity dispersion of σ ∼ 40 − 100 km s−1, in addition to a broader component with σ ∼ 100 − 300 km s−1, which contributes up to ∼40% of the total flux and is preferentially blueshifted from the systemic velocity. We interpret the narrow emission as highly ionized gas close to the young massive star clusters and the broader emission as a signpost of unresolved ionized outflows, resulting from massive stars and supernova feedback. We find a significant correlation between the width of the broad emission and the LyC escape fraction, with strong LCEs exhibiting more complex and broader line profiles than galaxies with weaker or undetected LyC emission. We provide new observational evidence supporting predictions from models and simulations; our findings suggest that gas turbulence and outflows resulting from strong radiative and mechanical feedback play a key role in clearing channels through which LyC photons escape from galaxies. We propose that the detection of blueshifted broad emission in the nebular lines of compact extreme emission-line galaxies can provide a new indirect diagnostic of Lyman photon escape, which could be useful to identify potential LyC leakers in the epoch of reionization with the JWST.
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| 7. |
- Dufies, M, et al.
(författare)
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Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1, s. 166-
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Tidskriftsartikel (refereegranskat)abstract
- Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
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| 8. |
- Fabritz, Larissa, et al.
(författare)
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Dynamic risk assessment to improve quality of care in patients with atrial fibrillation : the 7th AFNET/EHRA Consensus Conference
- 2021
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:3, s. 329-344
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes.Methods and resultsThis article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence.ConclusionThe remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy.
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| 9. |
- Kiekens, L, et al.
(författare)
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T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 732511-
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Tidskriftsartikel (refereegranskat)abstract
- T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.
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| 10. |
- Mehta, Vishal S., et al.
(författare)
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Machine learning-derived major adverse event prediction of patients undergoing transvenous lead extraction : Using the ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry
- 2022
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Ingår i: Heart Rhythm. - : Elsevier. - 1547-5271 .- 1556-3871. ; 19:6, s. 885-893
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Transvenous lead extraction (TLE) remains a high-risk procedure. OBJECTIVE The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict the risk of major adverse events (MAEs) after TLE. A MAE was defined as procedure-related major complication and procedure-related death. METHODS We designed and evaluated an ML-based risk stratification system trained using the European Lead Extraction ConTRolled (ELECTRa) registry to predict the risk of MAEs in 3555 patients undergoing TLE and tested this on an independent registry of 1171 patients. ML models were developed, including a self-normalizing neural network (SNN), stepwise logistic regression model ("stepwise model"), support vector machines, and random forest model. These were compared with the ELECTRa Registry Outcome Score (EROS) for MAEs. RESULTS There were 53 MAEs (1.7%) in the training cohort and 24 (2.4%) in the test cohort. Thirty-two clinically important features were used to train the models. ML techniques were similar to EROS by balanced accuracy (stepwise model: 0.74 vs EROS: 0.70) and superior by area under the curve (support vector machines: 0.764 vs EROS: 0.677). The SNN provided a finite risk for MAE and accurately identified MAE in 14 of 169 "high (<80%) risk" patients (8.3%) and no MAEs in all 198 "low (,20%) risk" patients (100%). CONCLUSION ML models incrementally improved risk prediction for identifying those at risk of MAEs. The SNN has the additional advantage of providing a personalized finite risk assessment for patients. This may aid patient decision making and allow better preoperative risk assessment and resource allocation.
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