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- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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- Van Den Bosch, T., et al.
(författare)
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Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding
- 2021
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:1, s. 164-172
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. Methods: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. Results: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19–92 years), median parity was 2 (range, 0–10) and median body mass index was 24.9 kg/m2 (range, 16.0–72.1 kg/m2). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0–5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4–3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2–1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6–3.4%)) cases with a single vessel without branching on unenhanced ultrasound. Conclusions: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely.
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- Hyde, Kevin D., et al.
(författare)
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One stop shop: backbones trees for important phytopathogenic genera: I (2014)
- 2014
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Ingår i: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 67:1, s. 21-125
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Tidskriftsartikel (refereegranskat)abstract
- Many fungi are pathogenic on plants and cause significant damage in agriculture and forestry. They are also part of the natural ecosystem and may play a role in regulating plant numbers/density. Morphological identification and analysis of plant pathogenic fungi, while important, is often hampered by the scarcity of discriminatory taxonomic characters and the endophytic or inconspicuous nature of these fungi. Molecular (DNA sequence) data for plant pathogenic fungi have emerged as key information for diagnostic and classification studies, although hampered in part by non-standard laboratory practices and analytical methods. To facilitate current and future research, this study provides phylogenetic synopses for 25 groups of plant pathogenic fungi in the Ascomycota, Basidiomycota, Mucormycotina (Fungi), and Oomycota, using recent molecular data, up-to-date names, and the latest taxonomic insights. Lineage-specific laboratory protocols together with advice on their application, as well as general observations, are also provided. We hope to maintain updated backbone trees of these fungal lineages over time and to publish them jointly as new data emerge. Researchers of plant pathogenic fungi not covered by the present study are invited to join this future effort. Bipolaris, Botryosphaeriaceae, Botryosphaeria, Botrytis, Choanephora, Colletotrichum, Curvularia, Diaporthe, Diplodia, Dothiorella, Fusarium, Gilbertella, Lasiodiplodia, Mucor, Neofusicoccum, Pestalotiopsis, Phyllosticta, Phytophthora, Puccinia, Pyrenophora, Pythium, Rhizopus, Stagonosporopsis, Ustilago and Verticillium are dealt with in this paper.
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- Smolen, JS, et al.
(författare)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update
- 2020
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:6, s. 685-699
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Tidskriftsartikel (refereegranskat)abstract
- To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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- De Cock, C., et al.
(författare)
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Organizing revolution?
- 2007
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Ingår i: Management & Organizational History. - : Informa UK Limited. - 1744-9359 .- 1744-9367. ; 2:2, s. 107-114
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Guerriero, Stefano, et al.
(författare)
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Age-related differences in the sonographic characteristics of endometriomas
- 2016
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 31:8, s. 1723-1731
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Tidskriftsartikel (refereegranskat)abstract
- Study Question Do sonographic characteristics of ovarian endometriomas vary with age in premenopausal women? Summary Answer With increasing age, multilocular cysts and cysts with papillations and other solid components become more common whereas ground glass echogenicity of cyst fluid becomes less common. What is Known Already Expectant or medical management of women with endometriomas is now accepted. Therefore, the accuracy of non-invasive diagnosis of these cysts is pivotal. A clinically relevant question is whether the sonographic characteristics of ovarian endometriomas are the same irrespective of the age of the woman. Study Design, Size, Duration This is a secondary analysis of cross-sectional data in the International Ovarian Tumor Analysis (IOTA) database. The database contains clinical and ultrasound information collected pre-operatively between 1999 and 2012 from 5914 patients with adnexal masses in 24 ultrasound centres in 10 countries. Participants/Materials, Setting, Methods There were 1005 histologically confirmed endometriomas in adult premenopausal patients found in the database and these were used in our analysis. The following ultrasound variables (defined using IOTA terminology) were used to describe the ultrasound appearance of the endometriomas: tender mass at ultrasound, largest diameter of lesion, tumour type (unilocular, unilocular-solid, multilocular, multilocular-solid, solid), echogenicity of cyst content, presence of papillations, number of papillations, height (mm) of largest papillation, presence and proportion of solid tissue and number of cyst locules, as well as vascularity in papillations and colour content of the tumour scan (colour score) on colour or power Doppler ultrasounds. Results are reported as median difference or odds ratio (OR) per 10 years increase in age. Main Results and the Role of Chance Maximal lesion diameter did not vary substantially with age (+1.3 mm difference per 10 years increase in age, 95% confidence interval (CI)-1.4 to 4.0). Tender mass at scan was less common in the older the woman (OR 0.75, 95% CI 0.63-0.89), as were unilocular cysts relative to multilocular cysts (OR 0.70, 95% CI 0.57-0.85) and to lesions with solid components (OR 0.61, 95% CI 0.48-0.77), and ground glass echogenicity relative to homogeneous low-level echogenicity (OR 0.74, 95% CI 0.58-0.94) and other types of echogenicity of cyst contents (OR 0.64, 95% CI 0.50-0.81). Papillations were more common the older the woman (OR 1.65, 95% CI 1.24-2.21), but their height and vascularization showed no clear relation to age. LIMITATIONS, REASONS FOR CAUTION It is a limitation that we have little clinical information on the women included, e.g. previous surgery or medical treatment for endometriosis. It is important to emphasize that we do not know the age of the endometrioma itself and that our study is not longitudinal and so does not describe changes in endometriomas over time. The differences in the ultrasound appearance of endometriomas between women of different ages might be explained by previous surgery or medical treatment and might not be an effect of age per se. Wider Implications of the Findings Awareness of physicians that the ultrasound appearance of endometriomas differs between women of different ages may facilitate a correct diagnosis of endometrioma. STUDY FUNDING/COMPETING INTEREST(S) This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750). B.V.C., A.C. and D.T. are supported by the Fund for Scientific Research Flanders, Belgium (FWO). The authors declare that there is no conflict of interest.
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