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- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Fredenberg, Erik, PhD, 1979-, et al.
(författare)
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Photon-Counting Spectral Phase-Contrast Mammography
- 2012
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Ingår i: Medical Imaging 2012. - : SPIE - International Society for Optical Engineering. - 9780819489623
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Konferensbidrag (refereegranskat)abstract
- Phase-contrast imaging is an emerging technology that may increase the signal-difference-to-noise ratio in medical imaging. One of the most promising phase-contrast techniques is Talbot interferometry, which, combined with energy-sensitive photon-counting detectors, enables spectral differential phase-contrast mammography. We have evaluated a realistic system based on this technique by cascaded-systems analysis and with a task-dependent ideal-observer detectability index as a figure-of-merit. Beam-propagation simulations were used for validation and illustration of the analytical framework. Differential phase contrast improved detectability compared to absorption contrast, in particular for fine tumor structures. This result was supported by images of human mastectomy samples that were acquired with a conventional detector. The optimal incident energy was higher in differential phase contrast than in absorption contrast when disregarding the setup design energy. Further, optimal weighting of the transmitted spectrum was found to have a weaker energy dependence than for absorption contrast. Taking the design energy into account yielded a superimposed maximum on both detectability as a function of incident energy, and on optimal weighting. Spectral material decomposition was not facilitated by phase contrast, but phase information may be used instead of spectral information.
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| 7. |
- Boj, Sylvia F, et al.
(författare)
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Organoid models of human and mouse ductal pancreatic cancer
- 2015
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Ingår i: Cell. - : Cell press. - 0092-8674 .- 1097-4172. ; 160:1-2, s. 324-338
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
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| 10. |
- Molnar, Miklos Z, et al.
(författare)
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Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans
- 2015
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 70:9, s. 888-895
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: There is a paucity of large cohort studies examining the association of obstructive sleep apnoea (OSA) with clinical outcomes including all-cause mortality, coronary heart disease (CHD), strokes and chronic kidney disease (CKD).OBJECTIVES: We hypothesised that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes.METHODS, MEASUREMENTS: In a nationally representative cohort of over 3 million (n=3 079 514) US veterans (93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m(2), we examined the association between the diagnosis of incident OSA, treated and untreated with CPAP, and: (1) all-cause mortality, (2) incident CHD, (3) incident strokes, (4)incident CKD defined as eGFR<60 mL/min/1.73 m(2), and (5) slopes of eGFR.MAIN RESULTS: Compared with OSA-negative patients, untreated and treated OSA was associated with 86% higher mortality risk, (adjusted HR and 95% CI 1.86 (1.81 to 1.91) and 35% (1.35 (1.21 to 1.51)), respectively. Similarly, untreated and treated OSA was associated with 3.5 times (3.54 (3.40 to 3.69)) and 3 times (3.06 (2.62 to 3.56)) higher risk of incident CHD; 3.5 times higher risk of incident strokes (3.48 (3.28 to 3.64) and 3.50 (2.92 to 4.19)) for untreated and treated OSA, respectively. The risk of incident CKD was also significantly higher in untreated (2.27 (2.19 to 2.36)) and treated (2.79 (2.48 to 3.13)) patients with OSA. The median (IQR) of the eGFR slope was -0.41 (-2.01 to 0.99), -0.61 (-2.69 to 0.93) and -0.87 (-3.00 to 0.70) mL/min/1.73 m(2) in OSA-negative patients, untreated OSA-positive patients and treated OSA-positive patients, respectively.CONCLUSIONS: In this large and contemporary cohort of more than 3 million US veterans, a diagnosis of incident OSA was associated with higher mortality, incident CHD, stroke and CKD and with faster kidney function decline.
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