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  • 1
    Online Resource
    Online Resource
    INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line
    Springer Science and Business Media LLC ; 2023
    In:  British Journal of Cancer Vol. 128, No. 8 ( 2023-04-12), p. 1503-1513
    Details
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 128, No. 8 ( 2023-04-12), p. 1503-1513
    Abstract: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p  = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). Conclusions This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6–12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. Clinical trial registration ClinicalTrials.gov, number NCT01379989.
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
    URL: Article
    DOI: 10.1038/s41416-022-02108-7
    RVK:
    XA 33500
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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  • 2
    Online Resource
    Online Resource
    Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial
    Springer Science and Business Media LLC ; 2022
    In:  Nature Medicine Vol. 28, No. 6 ( 2022-06), p. 1256-1268
    Details
    In: Nature Medicine, Springer Science and Business Media LLC, Vol. 28, No. 6 ( 2022-06), p. 1256-1268
    Abstract: Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5–20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n  = 164), patients with low/absent synovial B cell molecular signature had a lower response to rituximab (anti-CD20 monoclonal antibody) compared with that to tocilizumab (anti-IL6R monoclonal antibody) although the exact mechanisms of response/nonresponse remain to be established. Here, in-depth histological/molecular analyses of R4RA synovial biopsies identify humoral immune response gene signatures associated with response to rituximab and tocilizumab, and a stromal/fibroblast signature in patients refractory to all medications. Post-treatment changes in synovial gene expression and cell infiltration highlighted divergent effects of rituximab and tocilizumab relating to differing response/nonresponse mechanisms. Using ten-by-tenfold nested cross-validation, we developed machine learning algorithms predictive of response to rituximab (area under the curve (AUC) = 0.74), tocilizumab (AUC = 0.68) and, notably, multidrug resistance (AUC = 0.69). This study supports the notion that disease endotypes, driven by diverse molecular pathology pathways in the diseased tissue, determine diverse clinical and treatment–response phenotypes. It also highlights the importance of integration of molecular pathology signatures into clinical algorithms to optimize the future use of existing medications and inform the development of new drugs for refractory patients.
    Type of Medium: Online Resource
    ISSN: 1078-8956 , 1546-170X
    URL: Article
    DOI: 10.1038/s41591-022-01789-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1484517-9
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  • 3
    Online Resource
    Online Resource
    Case Reports * 1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGF  Receptor Mutations in Benign Joint Hypermobility
    Oxford University Press (OUP) ; 2013
    In:  Rheumatology Vol. 52, No. suppl 1 ( 2013-04-01), p. i56-i94
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 52, No. suppl 1 ( 2013-04-01), p. i56-i94
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/ket197
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
    detail.hit.zdb_id: 1474143-X
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  • 4
    Online Resource
    Online Resource
    Scientific Proceedings Second International Symposium on Cytostatic Drug Resistance
    Springer Science and Business Media LLC ; 1991
    In:  Journal of Cancer Research and Clinical Oncology Vol. 117, No. S3 ( 1991-5), p. S89-S120
    Details
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 117, No. S3 ( 1991-5), p. S89-S120
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    URL: Article
    DOI: 10.1007/BF01635345
    RVK:
    XA 52301
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1991
    detail.hit.zdb_id: 1459285-X
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  • 5
    Online Resource
    Online Resource
    Six transiting planets and a chain of Laplace resonances in TOI-178
    EDP Sciences ; 2021
    In:  Astronomy & Astrophysics Vol. 649 ( 2021-5), p. A26-
    Details
    In: Astronomy & Astrophysics, EDP Sciences, Vol. 649 ( 2021-5), p. A26-
    Abstract: Determining the architecture of multi-planetary systems is one of the cornerstones of understanding planet formation and evolution. Resonant systems are especially important as the fragility of their orbital configuration ensures that no significant scattering or collisional event has taken place since the earliest formation phase when the parent protoplanetary disc was still present. In this context, TOI-178 has been the subject of particular attention since the first TESS observations hinted at the possible presence of a near 2:3:3 resonant chain. Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and SPECULOOS with the aim of deciphering the peculiar orbital architecture of the system. We show that TOI-178 harbours at least six planets in the super-Earth to mini-Neptune regimes, with radii ranging from 1.152 −0.070 +0.073 to 2.87 −0.13 +0.14 Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and 20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of Laplace resonances, and the planetary densities show important variations from planet to planet, jumping from 1.02 −0.23 +0.28 to 0.177 −0.061 +0.055 times the Earth’s density between planets c and d . Using Bayesian interior structure retrieval models, we show that the amount of gas in the planets does not vary in a monotonous way, contrary to what one would expect from simple formation and evolution models and unlike other known systems in a chain of Laplace resonances. The brightness of TOI-178 ( H = 8.76 mag, J = 9.37 mag, V = 11.95 mag) allows for a precise characterisation of its orbital architecture as well as of the physical nature of the six presently known transiting planets it harbours. The peculiar orbital configuration and the diversity in average density among the planets in the system will enable the study of interior planetary structures and atmospheric evolution, providing important clues on the formation of super-Earths and mini-Neptunes.
    Type of Medium: Online Resource
    ISSN: 0004-6361 , 1432-0746
    URL: Article
    DOI: 10.1051/0004-6361/202039767
    RVK:
    UA 1000
    RVK:
    US 1090
    Language: English
    Publisher: EDP Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 1458466-9
    SSG: 16,12
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  • 6
    Online Resource
    Online Resource
    Investigating the architecture and internal structure of the TOI-561 system planets with CHEOPS, HARPS-N, and TESS
    Oxford University Press (OUP) ; 2022
    In:  Monthly Notices of the Royal Astronomical Society Vol. 511, No. 3 ( 2022-02-26), p. 4551-4571
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 511, No. 3 ( 2022-02-26), p. 4551-4571
    Abstract: We present a precise characterization of the TOI-561 planetary system obtained by combining previously published data with TESS and CHEOPS photometry, and a new set of 62 HARPS-N radial velocities (RVs). Our joint analysis confirms the presence of four transiting planets, namely TOI-561 b (P = 0.45 d, R = 1.42 R⊕, M = 2.0 M⊕), c (P = 10.78 d, R = 2.91 R⊕, M = 5.4 M⊕), d (P = 25.7 d, R = 2.82 R⊕, M = 13.2 M⊕), and e (P = 77 d, R = 2.55 R⊕, M = 12.6 R⊕). Moreover, we identify an additional, long-period signal ( & gt;450 d) in the RVs, which could be due to either an external planetary companion or to stellar magnetic activity. The precise masses and radii obtained for the four planets allowed us to conduct interior structure and atmospheric escape modelling. TOI-561 b is confirmed to be the lowest density (ρb = 3.8 ± 0.5 g cm−3) ultra-short period (USP) planet known to date, and the low metallicity of the host star makes it consistent with the general bulk density-stellar metallicity trend. According to our interior structure modelling, planet b has basically no gas envelope, and it could host a certain amount of water. In contrast, TOI-561 c, d, and e likely retained an H/He envelope, in addition to a possibly large water layer. The inferred planetary compositions suggest different atmospheric evolutionary paths, with planets b and c having experienced significant gas loss, and planets d and e showing an atmospheric content consistent with the original one. The uniqueness of the USP planet, the presence of the long-period planet TOI-561 e, and the complex architecture make this system an appealing target for follow-up studies.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/stac199
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 7
    Online Resource
    Online Resource
    TESS and CHEOPS discover two warm sub-Neptunes transiting the bright K-dwarf HD 15906
    Oxford University Press (OUP) ; 2023
    In:  Monthly Notices of the Royal Astronomical Society Vol. 523, No. 2 ( 2023-05-30), p. 3090-3118
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 523, No. 2 ( 2023-05-30), p. 3090-3118
    Abstract: We report the discovery of two warm sub-Neptunes transiting the bright (G = 9.5 mag) K-dwarf HD 15906 (TOI 461, TIC 4646810). This star was observed by the Transiting Exoplanet Survey Satellite (TESS) in sectors 4 and 31, revealing two small transiting planets. The inner planet, HD 15906 b, was detected with an unambiguous period but the outer planet, HD 15906 c, showed only two transits separated by ∼ 734 d, leading to 36 possible values of its period. We performed follow-up observations with the CHaracterising ExOPlanet Satellite (CHEOPS) to confirm the true period of HD 15906 c and improve the radius precision of the two planets. From TESS, CHEOPS, and additional ground-based photometry, we find that HD 15906 b has a radius of 2.24 ± 0.08 R⊕ and a period of 10.924709 ± 0.000032 d, whilst HD 15906 c has a radius of 2.93$^{+0.07}_{-0.06}$ R⊕ and a period of 21.583298$^{+0.000052}_{-0.000055}$ d. Assuming zero bond albedo and full day-night heat redistribution, the inner and outer planet have equilibrium temperatures of 668 ± 13 K and 532 ± 10 K, respectively. The HD 15906 system has become one of only six multiplanet systems with two warm (≲ 700 K) sub-Neptune sized planets transiting a bright star (G ≤ 10 mag). It is an excellent target for detailed characterization studies to constrain the composition of sub-Neptune planets and test theories of planet formation and evolution.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/stad1369
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 8
    Online Resource
    Online Resource
    CHEOPS observations of the HD 108236 planetary system: a fifth planet, improved ephemerides, and planetary radii
    EDP Sciences ; 2021
    In:  Astronomy & Astrophysics Vol. 646 ( 2021-2), p. A157-
    Details
    In: Astronomy & Astrophysics, EDP Sciences, Vol. 646 ( 2021-2), p. A157-
    Abstract: Context. The detection of a super-Earth and three mini-Neptunes transiting the bright ( V = 9.2 mag) star HD 108236 (also known as TOI-1233) was recently reported on the basis of TESS and ground-based light curves. Aims. We perform a first characterisation of the HD 108236 planetary system through high-precision CHEOPS photometry and improve the transit ephemerides and system parameters. Methods. We characterise the host star through spectroscopic analysis and derive the radius with the infrared flux method. We constrain the stellar mass and age by combining the results obtained from two sets of stellar evolutionary tracks. We analyse the available TESS light curves and one CHEOPS transit light curve for each known planet in the system. Results. We find that HD 108236 is a Sun-like star with R ⋆ = 0.877 ± 0.008 R ⊙ , M ⋆ = 0.869 −0.048 +0.050 M ⊙ , and an age of 6.7 −5.1 +4.0 Gyr. We report the serendipitous detection of an additional planet, HD 108236 f, in one of the CHEOPS light curves. For this planet, the combined analysis of the TESS and CHEOPS light curves leads to a tentative orbital period of about 29.5 days. From the light curve analysis, we obtain radii of 1.615 ± 0.051, 2.071 ± 0.052, 2.539 −0.065 +0.062 , 3.083 ± 0.052, and 2.017 −0.057 +0.052 R ⊕ for planets HD 108236 b to HD 108236 f, respectively. These values are in agreement with previous TESS-based estimates, but with an improved precision of about a factor of two. We perform a stability analysis of the system, concluding that the planetary orbits most likely have eccentricities smaller than 0.1. We also employ a planetary atmospheric evolution framework to constrain the masses of the five planets, concluding that HD 108236 b and HD 108236 c should have an Earth-like density, while the outer planets should host a low mean molecular weight envelope. Conclusions. The detection of the fifth planet makes HD 108236 the third system brighter than V = 10 mag to host more than four transiting planets. The longer time span enables us to significantly improve the orbital ephemerides such that the uncertainty on the transit times will be of the order of minutes for the years to come. A comparison of the results obtained from the TESS and CHEOPS light curves indicates that for a V ~ 9 mag solar-like star and a transit signal of ~500 ppm, one CHEOPS transit light curve ensures the same level of photometric precision as eight TESS transits combined, although this conclusion depends on the length and position of the gaps in the light curve.
    Type of Medium: Online Resource
    ISSN: 0004-6361 , 1432-0746
    URL: Article
    DOI: 10.1051/0004-6361/202039608
    RVK:
    UA 1000
    RVK:
    US 1090
    Language: English
    Publisher: EDP Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 1458466-9
    SSG: 16,12
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  • 9
    Online Resource
    Online Resource
    The hot dayside and asymmetric transit of WASP-189 b seen by CHEOPS
    EDP Sciences ; 2020
    In:  Astronomy & Astrophysics Vol. 643 ( 2020-11), p. A94-
    Details
    In: Astronomy & Astrophysics, EDP Sciences, Vol. 643 ( 2020-11), p. A94-
    Abstract: The CHEOPS space mission dedicated to exoplanet follow-up was launched in December 2019, equipped with the capacity to perform photometric measurements at the 20 ppm level. As CHEOPS carries out its observations in a broad optical passband, it can provide insights into the reflected light from exoplanets and constrain the short-wavelength thermal emission for the hottest of planets by observing occultations and phase curves. Here, we report the first CHEOPS observation of an occultation, namely, that of the hot Jupiter WASP-189 b, a M P ≈ 2 M J planet orbiting an A-type star. We detected the occultation of WASP-189 b at high significance in individual measurements and derived an occultation depth of dF = 87.9 ± 4.3 ppm based on four occultations. We compared these measurements to model predictions and we find that they are consistent with an unreflective atmosphere heated to a temperature of 3435 ± 27 K, when assuming inefficient heat redistribution. Furthermore, we present two transits of WASP-189 b observed by CHEOPS. These transits have an asymmetric shape that we attribute to gravity darkening of the host star caused by its high rotation rate. We used these measurements to refine the planetary parameters, finding a ~25% deeper transit compared to the discovery paper and updating the radius of WASP-189 b to 1.619 ± 0.021 R J . We further measured the projected orbital obliquity to be λ = 86.4 −4.4 +2.9° , a value that is in good agreement with a previous measurement from spectroscopic observations, and derived a true obliquity of Ψ = 85.4 ± 4.3°. Finally, we provide reference values for the photometric precision attained by the CHEOPS satellite: for the V = 6.6 mag star, and using a 1-h binning, we obtain a residual RMS between 10 and 17 ppm on the individual light curves, and 5.7 ppm when combining the four visits.
    Type of Medium: Online Resource
    ISSN: 0004-6361 , 1432-0746
    URL: Article
    DOI: 10.1051/0004-6361/202038677
    RVK:
    UA 1000
    RVK:
    US 1090
    Language: English
    Publisher: EDP Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 1458466-9
    SSG: 16,12
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  • 10
    Online Resource
    Online Resource
    A full transit of v 2 Lupi d and the search for an exomoon in its Hill sphere with CHEOPS
    EDP Sciences ; 2023
    In:  Astronomy & Astrophysics Vol. 671 ( 2023-3), p. A154-
    Details
    In: Astronomy & Astrophysics, EDP Sciences, Vol. 671 ( 2023-3), p. A154-
    Abstract: The planetary system around the naked-eye star v 2 Lupi (HD 136352; TOI-2011) is composed of three exoplanets with masses of 4.7, 11.2, and 8.6 Earth masses ( M ⊕ ). The TESS and CHEOPS missions revealed that all three planets are transiting and have radii straddling the radius gap separating volatile-rich and volatile-poor super-earths. Only a partial transit of planet d had been covered so we re-observed an inferior conjunction of the long-period 8.6 M ⊕ exoplanet v 2 Lup d with the CHEOPS space telescope. We confirmed its transiting nature by covering its whole 9.1 h transit for the first time. We refined the planet transit ephemeris to P = 107.1361 −0.0022 +0.0019 days and T c = 2459009.7759 −0.0096 +0.0101 BJD TDB , improving by ~40 times on the previously reported transit timing uncertainty. This refined ephemeris will enable further follow-up of this outstanding long-period transiting planet to search for atmospheric signatures or explore the planet’s Hill sphere in search for an exomoon. In fact, the CHEOPS observations also cover the transit of a large fraction of the planet’s Hill sphere, which is as large as the Earth’s, opening the tantalising possibility of catching transiting exomoons. We conducted a search for exomoon signals in this single-epoch light curve but found no conclusive photometric signature of additional transiting bodies larger than Mars. Yet, only a sustained follow-up of v 2 Lup d transits will warrant a comprehensive search for a moon around this outstanding exoplanet.
    Type of Medium: Online Resource
    ISSN: 0004-6361 , 1432-0746
    URL: Article
    DOI: 10.1051/0004-6361/202244790
    RVK:
    UA 1000
    RVK:
    US 1090
    Language: English
    Publisher: EDP Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 1458466-9
    SSG: 16,12
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