| 1. |
- Boada, Mercè, et al.
(författare)
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Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease : Results from the MOPEAD project
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:6, s. 1119-1127
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. Methods: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care–based protocol for early detection of cognitive decline (PC), and (4) a tertiary care–based pre-screening at diabetologist clinics (DC). Results: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). Conclusion: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD.
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| 2. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 3. |
- Alexandrov, Ludmil B., et al.
(författare)
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Signatures of mutational processes in human cancer
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 500:7463, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
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| 4. |
- Garg, Scot, et al.
(författare)
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Prediction of 1-year clinical outcomes using the SYNTAX score in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention : a substudy of the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials
- 2011
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Ingår i: JACC: Cardiovascular interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 4:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThis study sought to evaluate the impact of SYNTAX score (SXscore), and compare its performance in isolation and combination with the PAMI (The Primary Angioplasty in Myocardial Infarction Study) score, for the prediction of 1-year clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention.BackgroundPatients with STEMI were excluded from the original SYNTAX score (SXscore) algorithm. Therefore, the utility of using the SXscore in this patient group remains undefined.MethodsSXscore was calculated retrospectively in 807 patients with STEMI enrolled in the randomized STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) clinical trials. Clinical outcomes of all-cause death, reinfarction, and clinically driven target vessel revascularization were subsequently stratified according to SXscore tertiles: SXLOW ≤9 (n = 311), 9 < SXMID ≤16 (n = 234), SXHIGH >16 (n = 262).ResultsAt 1-year follow-up, all clinical outcomes including mortality, mortality/reinfarction, major adverse cardiac events (MACE) (a composite of all-cause death, reinfarction and target vessel revascularization), and definite, definite/probable, and any stent thrombosis were all significantly higher in patients in the highest SXscore tertile. SXscore was identified as an independent predictor of mortality, MACE, and stent thrombosis out to 1-year follow-up. The combination SYNTAX-PAMI score led to a net reclassification improvement of 15.7% and 4.6% for mortality and MACE, respectively. The C-statistics for the SXscore, PAMI score, and the combined SYNTAX-PAMI score were 0.65, 0.81, and 0.73 for 1-year mortality, and 0.68, 0.64, and 0.69 for 1-year MACE, respectively.ConclusionsSXscore does have a role in the risk stratification of patients with STEMI having primary percutaneous coronary intervention; however, this ability can be improved through a combination with clinical variables. (Multicentre 2×2 Factorial Randomised Study Comparing Tirofiban Versus Abciximab and SES Versus BMS in AMI; NCT00229515)
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| 5. |
- Gonzalez, J. M., et al.
(författare)
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Genome analysis of the proteorhodopsin-containing marine bacterium Polaribacter sp. MED152 (Flavobacteria)
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:25, s. 8724-8729
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of marine cyanobacteria and proteobacteria genomes has provided a profound understanding of the life strategies of these organisms and their ecotype differentiation and metabolisms. However, a comparable analysis of the Bacteroidetes, the third major bacterioplankton group, is still lacking. In the present paper, we report on the genome of Polaribacter sp. strain MED152. On the one hand, MED152 contains a substantial number of genes for attachment to surfaces or particles, gliding motility, and polymer degradation. This agrees with the currently assumed life strategy of marine Bacteroidetes. On the other hand, it contains the proteorhoclopsin gene, together with a remarkable suite of genes to sense and respond to light, which may provide a survival advantage in the nutrient-poor sun-lit ocean surface when in search of fresh particles to colonize. Furthermore, an increase in CO2 fixation in the light suggests that the limited central metabolism is complemented by anaplerotic inorganic carbon fixation. This is mediated by a unique combination of membrane transporters and carboxylases. This suggests a dual life strategy that, if confirmed experimentally, would be notably different from what is known of the two other main bacterial groups (the autotrophic cyanobacteria and the heterotrophic proteobacteria) in the surface oceans. The Polaribacter genome provides insights into the physiological capabilities of proteorhodopsin-containing bacteria. The genome will serve as a model to study the cellular and molecular processes in bacteria that express proteorhoclopsin, their adaptation to the oceanic environment, and their role in carbon-cycling.
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| 6. |
- Hamm, Michael, et al.
(författare)
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BRN2 is a non-canonical melanoma tumor-suppressor
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- While the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600EPtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.
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| 7. |
- Meeter, Lieke H.H., et al.
(författare)
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Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia
- 2019
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 90:9, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods: This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results: CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs=-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs=-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion: CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.
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| 8. |
- Pujade-Lauraine, Eric, et al.
(författare)
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Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer : A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:7, s. 706-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
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| 9. |
- Rodriguez-Martinez, Xabier, et al.
(författare)
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Microfluidic-Assisted Blade Coating of Compositional Libraries for Combinatorial Applications: The Case of Organic Photovoltaics
- 2020
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Ingår i: Advanced Energy Materials. - : WILEY-V C H VERLAG GMBH. - 1614-6832 .- 1614-6840. ; 10:33
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Tidskriftsartikel (refereegranskat)abstract
- Microfluidic technologies are highly adept at generating controllable compositional gradients in fluids, a feature that has accelerated the understanding of the importance of chemical gradients in biological processes. That said, the development of versatile methods to generate controllable compositional gradients in the solid-state has been far more elusive. The ability to produce such gradients would provide access to extensive compositional libraries, thus enabling the high-throughput exploration of the parametric landscape of functional solids and devices in a resource-, time-, and cost-efficient manner. Herein, the synergic integration of microfluidic technologies is reported with blade coating to enable the controlled formation of compositional lateral gradients in solution. Subsequently, the transformation of liquid-based compositional gradients into solid-state thin films using this method is demonstrated. To demonstrate efficacy of the approach, microfluidic-assisted blade coating is used to optimize blending ratios in organic solar cells. Importantly, this novel technology can be easily extended to other solution processable systems that require the formation of solid-state compositional lateral gradients.
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| 10. |
- Sannemann, Lena, et al.
(författare)
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General practitioners’ attitude toward early and pre-dementia diagnosis of ad in five European countries—a mopead project survey
- 2021
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer’s Disease project, we assess GPs’ attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis. Methods: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries. Results: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs’ perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis. Discussion: Our findings provide insight into GPs’ attitudes by exploring differences in perception and management of early diagnosis.
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