| 1. |
- Rubio-San-Simón, Alba, et al.
(författare)
-
Impact of COVID-19 in paediatric early-phase cancer clinical trials in Europe: A report from the Innovative Therapies for Children with Cancer (ITCC) consortium.
- 2020
-
Ingår i: European journal of cancer (Oxford, England : 1990). - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 141, s. 82-91
-
Tidskriftsartikel (refereegranskat)abstract
- Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC).A survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020.Thirty-one of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared with that in 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. In addition, 26% of sites had restrictions on performing trial assessments because of local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organisational and structural changes.The study reveals a profound disruption of paediatric cancer early-phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises.
|
|
| 2. |
- Flex, Elisabetta, et al.
(författare)
-
Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:16, s. 4315-4327
-
Tidskriftsartikel (refereegranskat)abstract
- RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
|
|
| 3. |
- Philippe, Marc, et al.
(författare)
-
Life in the woods: Taphonomic evolution of a diverse saproxylic community within fossil woods from Upper Cretaceous submarine mass flow deposits (Mzamba Formation, southeast Africa)
- 2022
-
Ingår i: Gondwana Research. - Amsterdam : Elsevier. - 1342-937X .- 1878-0571. ; 109, s. 113-133
-
Tidskriftsartikel (refereegranskat)abstract
- Organisms that colonize wood are subject to a taphonomic tragedy—the richer and more diverse they become, the greater the deterioration of the host wood and the less likely such communities are to be fossilized. Moreover, palaeobotanical studies of fossil wood usually focus on the plant tissue, neglecting the evidence of parasitic, saproxylic, and other contained organisms. Such a case involved a relatively well-known fossil wood assemblage from the Santonian (Late Cretaceous, ca 84 Ma) of southeast Africa. In a set of 150 thin sections of silicified wood stored in the Senckenburg Museum for more than half a century, we discovered evidence of a diverse biotic community comprising bacteria, fungi, nematodes, several types of arthropods, and marine bivalves. These body fossils and traces, together with growth-ring features, fossil log size and shape, and the distribution of glauconite, facilitated interpretation of the multi-stage evolution of a wood-hosted biocoenosis of unprecedented diversity. This record is unique for the Mesozoic and is of importance for understanding the taphonomic pathways to preservation and the evolution and diversification of saproxylic and other wood-hosted communities in terrestrial and marine settings.
|
|
