| 1. |
- Alvez, Maria Bueno, et al.
(author)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 2. |
- Bergquist, Filip, et al.
(author)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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In: Neurology. - : Lippincott, Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 99:10, s. E965-E976
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Journal article (peer-reviewed)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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| 3. |
- Boissin, Constance, et al.
(author)
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Development and evaluation of deep learning algorithms for assessment of acute burns and the need for surgery
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Assessment of burn extent and depth are critical and require very specialized diagnosis. Automated image-based algorithms could assist in performing wound detection and classification. We aimed to develop two deep-learning algorithms that respectively identify burns, and classify whether they require surgery. An additional aim assessed the performances in different Fitzpatrick skin types. Annotated burn (n = 1105) and background (n = 536) images were collected. Using a commercially available platform for deep learning algorithms, two models were trained and validated on 70% of the images and tested on the remaining 30%. Accuracy was measured for each image using the percentage of wound area correctly identified and F1 scores for the wound identifier; and area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity for the wound classifier. The wound identifier algorithm detected an average of 87.2% of the wound areas accurately in the test set. For the wound classifier algorithm, the AUC was 0.885. The wound identifier algorithm was more accurate in patients with darker skin types; the wound classifier was more accurate in patients with lighter skin types. To conclude, image-based algorithms can support the assessment of acute burns with relatively good accuracy although larger and different datasets are needed.
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| 4. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(author)
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The SELMA study : a birth cohort study in Sweden following more than 2000 mother-child pairs
- 2012
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In: Paediatric and Perinatal Epidemiology. - Hoboken, USA : Wiley-Blackwell. - 0269-5022 .- 1365-3016. ; 26:5, s. 456-467
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Journal article (peer-reviewed)abstract
- Background: This paper describes the background, aim and study design for the Swedish SELMA study that aimed to investigate the importance of early life exposure during pregnancy and infancy to environmental factors with a major focus on endocrine disrupting chemicals for multiple chronic diseases/disorders in offspring.Methods: The cohort was established by recruiting women in the 10th week of pregnancy. Blood and urine from the pregnant women and the child and air and dust from home environment from pregnancy and infancy period have been collected. Questionnaires were used to collect information on life styles, socio-economic status, living conditions, diet and medical history.Results: Of the 8394 reported pregnant women, 6658 were invited to participate in the study. Among the invited women, 2582 (39%) agreed to participate. Of the 4076 (61%) non-participants, 2091 women were invited to a non-respondent questionnaire in order to examine possible selection bias. We found a self-selection bias in the established cohort when compared with the non-participant group, e.g. participating families did smoke less (14% vs. 19%), had more frequent asthma and allergy symptoms in the family (58% vs. 38%), as well as higher education among the mothers (51% vs. 36%) and more often lived in single-family houses (67% vs. 60%).Conclusions: These findings indicate that the participating families do not fully represent the study population and thus, the exposure in this population. However, there is no obvious reason that this selection bias will have an impact on identification of environmental risk factors.
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| 5. |
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| 6. |
- Gad, Helge, et al.
(author)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Journal article (peer-reviewed)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 7. |
- Geijer Lundin, Erik, et al.
(author)
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Adaptive Filtering Applied to an Uplink Load Estimate in WCDMA
- 2003
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In: Proceedings of the 57th IEEE Semiannual Vehicular Technology Conference. - Linköping : Linköping University Electronic Press. - 0780377575 ; , s. 452-456
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Conference paper (peer-reviewed)abstract
- In the uplink of a WCDMA system, a natural choice of resource quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure and estimates are often noisy. This paper focuses on relative load which is closely related to the noise rise. Model-based signal processing with change detection techniques is herein used to suppress noise and minor oscillations while being alert on fast load changes. The time varying model identified in the process can also be used for prediction of future values, something which resource management algorithms can benefit from.
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| 8. |
- Geijer Lundin, Erik, et al.
(author)
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Robust Uplink Resource Allocation in CDMA Cellular Radio Systems
- 2005
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In: Proceedings of the 44th IEEE Conference on Decision and Control and European Control Conference 2005. - Linköping : Linköping University Electronic Press. - 0780395670 ; , s. 1848-1853
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Conference paper (peer-reviewed)abstract
- Radio resource management (RRM) in cellular radio system is an example of automatic control. The system performance may be increased by introducing decentralization, shorter delays and increased adaptation to local demands. However, it is hard to guarantee system stability without being, too conservative while using decentralized resource management. In this paper, two algorithms that both guarantee system stability and use local resource control are proposed for the uplink (mobile to base station). While one of the algorithms uses only local decisions, the other uses a central node to coordinate resources among different local nodes. In the chosen design approach, a feasible solution to the optimization problems corresponds to a stable system. Therefore, the algorithms will never assign resources that lead to an unstable system. Simulations indicate that the proposed algorithms also provide high capacity at any given uplink load level.
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| 9. |
- Geijer Lundin, Erik, et al.
(author)
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Uplink Load Estimates in WCDMA with Different Availability of Measurements
- 2003
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In: Proceedings of the 57th IEEE Semiannual Vehicular Technology Conference. - Linköping : Linköping University Electronic Press. - 0780377575 ; , s. 1198-1202 vol.2
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Conference paper (peer-reviewed)abstract
- In the uplink of a WCDMA system, a natural choice of resource management control quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure. In this paper, we propose and evaluate a number of noise rise estimates which all rely on path gain measurements. These measurements can be made available either periodically or event-driven as described in 3GPP (Release 99). Simulations show that event-driven measurements yield comparable performance to periodic measurements, but with much fewer measurement reports. Despite severely limited path gain knowledge due to that some users report to another RNC, we still manage to estimate the uplink noise rise reasonably well.
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| 10. |
- Geijer Lundin, Erik, et al.
(author)
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Uplink Load Estimation in WCDMA
- 2003
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In: Proceedings of the 2003 IEEE Wireless Communications and Networking. - 0780377001 ; , s. 1669-1674 vol.3
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Conference paper (peer-reviewed)abstract
- All cellular radio systems have radio resource management algorithms which rely on some sort of resource quantity. In the uplink of a WCDMA system, a natural choice of such a quantity is the uplink noise rise, i.e., total received power over noise power. Unfortunately this quantity is hard to measure. In this paper, we propose and evaluate four different noise rise 711 estimates. The best performing estimate provides an average error of less than 1 dB for practical load levels. Due to low standard deviation of single estimates it is possible to apply a simple error correction algorithm.
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