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- van Bragt, JJMH, et al.
(author)
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Characteristics and treatment regimens across ERS SHARP severe asthma registries
- 2020
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 55:1
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Journal article (peer-reviewed)abstract
- Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m−2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day−1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day−1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.
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| 2. |
- Ortiz-Fernandez, Lourdes, et al.
(author)
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Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
- 2021
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In: American Journal of Human Genetics. - CAMBRIDGE, MA USA : Cell Press. - 0002-9297 .- 1537-6605. ; 108:1, s. 84-99
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Journal article (peer-reviewed)abstract
- Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
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| 4. |
- Marazioti, Antonia, et al.
(author)
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KRAS signaling in malignant pleural mesothelioma
- 2022
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 14:2
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Journal article (peer-reviewed)abstract
- Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM-like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.
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| 7. |
- Yavuz, Sule, et al.
(author)
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Mer-tyrosine kinase : a novel susceptibility gene for SLE related end-stage renal disease
- 2022
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In: Lupus Science and Medicine. - : BMJ Publishing Group Ltd. - 2053-8790. ; 9:1
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Journal article (peer-reviewed)abstract
- Objective Lupus nephritis (LN) is a common and severe manifestation of SLE. The genetic risk for nephritis and progression to end-stage renal disease (ESRD) in patients with LN remains unclear. Herein, we aimed to identify novel genetic associations with LN, focusing on subphenotypes and ESRD. Methods We analysed genomic data on 958 patients with SLE (discovery cohort: LN=338) with targeted sequencing data from 1832 immunological pathway genes. We used an independent multiethnic cohort comprising 1226 patients with SLE (LN=603) as a replication dataset. Detailed functional annotation and functional epigenomic enrichment analyses were applied to predict functional effects of the candidate variants. Results A genetic variant (rs56097910) within the MERTK gene was associated with ESRD in both cohorts, meta-analysis OR=5.4 (2.8 to 10.6); p=1.0×10-6. We observed decreased methylation levels in peripheral blood cells from SLE patients with ESRD, compared with patients without renal SLE (p=2.7×10-4), at one CpG site (cg16333401) in close vicinity to the transcription start site of MERTK and located in a DNAse hypersensitivity region in T and B cells. Rs56097910 is linked to altered MERTK expression in kidney tissue in public eQTL databases. Two loci were replicated for association with proliferative LN: PRDM1 (rs6924535, p meta =1.6×10-5, OR=0.58) and APOA1BP (NAXE) (rs942960, p meta =1.2×10-5, OR=2.64). Conclusion We identified a novel genetic risk locus, MERTK, associated with SLE-ESRD using the data from two large SLE cohorts. Through DNA methylation analysis and functional annotation, we showed that the risk could be mediated through regulation of gene expression. Our results suggest that variants in the MERTK gene are important for the risk of developing SLE-ESRD and suggest a role for PRDM1 and APOA1BP in proliferative LN.
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| 8. |
- Arslan, M. Tunc, et al.
(author)
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Rapid TAURUS for Relaxation-Based Color Magnetic Particle Imaging
- 2022
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In: IEEE Transactions on Medical Imaging. - : Institute of Electrical and Electronics Engineers (IEEE). - 0278-0062 .- 1558-254X. ; 41:12, s. 3774-3786
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Journal article (peer-reviewed)abstract
- Magnetic particle imaging (MPI) is a rapidly developing medical imaging modality that exploits the non- linear response of magnetic nanoparticles (MNPs). Color MPI widens the functionality of MPI, empowering it with the capability to distinguish differentMNPs and/orMNP environments. The system function approach for color MPI relies on extensive calibrations that capture the differences in the harmonic responses of the MNPs. An alternative calibration-free x-space-basedmethod called TAURUS estimates amap of the relaxation time constant, tau, by recovering the underlyingmirror symmetry in the MPI signal. However, TAURUS requires a back and forth scanning of a given region, restricting its usage to slow trajectories with constant or piecewise constant focus fields (FFs). In this work, we propose a novel technique to increase the performance of TAURUS and enable tau map estimation for rapid andmultidimensional trajectories. The proposed technique is based on correcting the distortions on mirror symmetry induced by time-varying FFs. We demonstrate via simulations and experiments in our in-house MPI scanner that the proposed method successfully estimates high-fidelity tau maps for rapid trajectories that provide orders of magnitude reduction in scanning time (over 300 fold for simulations and over 8 fold for experiments) while preserving the calibration-free property of TAURUS.
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| 9. |
- Essalhi, Mohamed, et al.
(author)
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Development of a Lycopodium powder-based superhydrophobic nanofiber membrane suitable for desalination
- 2023
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In: Separation and Purification Technology. - : Elsevier. - 1383-5866 .- 1873-3794. ; 323
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Journal article (peer-reviewed)abstract
- A biobased, green, inexpensive additive, Lycopodium particles, which are spores of the “Lycopodium clavatum” plant, were incorporated in the poly(vinylidene fluoride) PVDF electrospun nanofiber membranes (ENMs) for desalination by direct contact membrane distillation (DCMD). Superhydrophobic ENMs were prepared using this additive (PVDF-ENMs-Lyc). Thanks to their morphological structure and their prominent surface superhydrophobicity (anti-wetting) character, the resulting PVDF-ENMs-Lyc exhibited an improved liquid entry pressure (LEP), a high void volume fraction (greater than 87.2%), a good salt rejection factor (greater than 99.93%) and a reasonably high permeate flux (greater than 51.76 kg·m-2·h-1) at 80 °C, which are of great practical importance for water desalination by DCMD. The optimum membrane prepared with 3 wt% Lycopodium in the dope solution demonstrated a stable permeate flux of 52.4 ± 0.6 kg·m-2·h-1 with an electrical conductivity around 4.76 ± 0.46 μS/cm (NaCl rejection factor of 99.998 ± 0.036%) during 25 h DCMD desalination experiment using 35 g/L NaCl aqueous solution (similar to seawater concentration). The presented results pave the way for superhydrophobic nanofibrous membrane engineering suitable for membrane contactors by electrospinning in a single step without surfactants, organic additives, or chemical post-treatments, just by the incorporation of a green additive like Lycopodium powder.
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| 10. |
- Gaget, Elie, et al.
(author)
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Benefits of protected areas for nonbreeding waterbirds adjusting their distributions under climate warming
- 2021
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In: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 35:3, s. 834-845
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Journal article (peer-reviewed)abstract
- Climate warming is driving changes in species distributions and community composition. Many species have a so-called climatic debt, that is, shifts in range lag behind shifts in temperature isoclines. Inside protected areas (PAs), community changes in response to climate warming can be facilitated by greater colonization rates by warm-dwelling species, but also mitigated by lowering extirpation rates of cold-dwelling species. An evaluation of the relative importance of colonization-extirpation processes is important to inform conservation strategies that aim for both climate debt reduction and species conservation. We assessed the colonization-extirpation dynamics involved in community changes in response to climate inside and outside PAs. To do so, we used 25 years of occurrence data of nonbreeding waterbirds in the western Palearctic (97 species, 7071 sites, 39 countries, 1993–2017). We used a community temperature index (CTI) framework based on species thermal affinities to investigate species turnover induced by temperature increase. We determined whether thermal community adjustment was associated with colonization by warm-dwelling species or extirpation of cold-dwelling species by modeling change in standard deviation of the CTI (CTISD). Using linear mixed-effects models, we investigated whether communities in PAs had lower climatic debt and different patterns of community change than communities outside PAs. For CTI and CTISD combined, communities inside PAs had more species, higher colonization, lower extirpation, and lower climatic debt (16%) than communities outside PAs. Thus, our results suggest that PAs facilitate 2 independent processes that shape community dynamics and maintain biodiversity. The community adjustment was, however, not sufficiently fast to keep pace with the large temperature increases in the central and northeastern western Palearctic. Our results underline the potential of combining CTI and CTISD metrics to improve understanding of the colonization-extirpation patterns driven by climate warming.
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