| 6751. |
- Sopasakis, Alexandros, et al.
(författare)
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Machine learning evaluation for identification of M-proteins in human serum
- 2024
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Ingår i: PLoS ONE. - 1932-6203. ; 19:4, s. 0299600-0299600
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Tidskriftsartikel (refereegranskat)abstract
- Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery. In this study we compared 26 different decision tree algorithms to identify the presence of M-proteins in human serum by using numerical data from serum protein capillary electrophoresis. For the automated detection and clustering of data, we used an anonymized data set consisting of 67,073 samples. We found five methods with superior ability to detect M-proteins: Extra Trees (ET), Random Forest (RF), Histogram Grading Boosting Regressor (HGBR), Light Gradient Boosting Method (LGBM), and Extreme Gradient Boosting (XGB). Additionally, we implemented a game theoretic approach to disclose which features in the data set that were indicative of the resulting M-protein diagnosis. The results verified the gamma globulin fraction and part of the beta globulin fraction as the most important features of the electrophoresis analysis, thereby further strengthening the reliability of our approach. Finally, we tested the algorithms for classifying the M-protein isotypes, where ET and XGB showed the best performance out of the five algorithms tested. Our results show that serum capillary electrophoresis combined with decision tree algorithms have great potential in the application of rapid and accurate identification of M-proteins. Moreover, these methods would be applicable for a variety of blood analyses, such as hemoglobinopathies, indicating a wide-range diagnostic use. However, for M-protein isotype classification, combining machine learning solutions for numerical data from capillary electrophoresis with gel electrophoresis image data would be most advantageous.
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| 6752. |
- Sorberg, A., et al.
(författare)
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Body Mass Index in Young Adulthood and Suicidal Behavior up to Age 59 in a Cohort of Swedish Men
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- An association of higher body mass index (BMI) with lower risk of attempted and completed suicide has been reported. In contrast, increasing BMI has been found to be associated with depression and other risk factors for suicidal behavior. We aimed to investigate this possible paradox in a cohort comprising 49 000 Swedish men. BMI, mental health, lifestyle and socioeconomic measures were recorded at conscription in 1969-70, at ages 18-20. Information on attempted suicide 1973-2008 and completed suicide 1971-2008 was obtained from national records. Hazard ratios (HR) were estimated by Cox proportional hazard models. We found that each standard deviation (SD) increase in BMI was associated with a 12% lower risk of later suicide attempt (HR 0.88, 95% CI 0.83-0.94). Associations were somewhat weaker for completed suicide and did not reach conventional levels of statistical significance (HR 0.93, 95% CI 0.85-1.01). Adjustment for a wide range of possible confounding factors had little effect on the associations. Lower BMI at conscription was also associated with higher prevalence of psychiatric diagnoses, low emotional control and depressed mood. Our results confirm previous findings regarding the association of higher BMI with a reduced risk of suicide, extending them to show similar findings in relation to suicide attempts. The associations were little affected by adjustment for a range of possible confounding factors. However, we found no evidence that high BMI was associated with an increased risk of depression cross-sectionally or longitudinally.
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| 6753. |
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| 6754. |
- Sorbye, Halfdan, et al.
(författare)
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High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- RAS and BRAF mutations impact treatment and prognosis of metastatic colorectal cancer patients (mCRC), but the knowledge is based on trial patients usually not representative for the general cancer population. Patient characteristics, treatment and efficacy according to KRAS, BRAF and MSI status were analyzed in a prospectively collected unselected population-based cohort of 798 non-resectable mCRC patients. The cohort contained many patients with poor performance status (39% PS 2-4) and elderly (37% age>75), groups usually not included in clinical trials. Patients without available tissue micro array (TMA) (42%) had worse prognostic factors and inferior survival (all patients; 7m vs 11m, chemotherapy-treated; 12m vs 17m). The 92 patients (21%) with BRAF mutation had a poor prognosis regardless of microsatellite instability, but receipt of 1-2nd chemotherapy was similar to wildtype BRAF patients. Median survival in this cohort varied from 1 month in BRAF mutated patients not given chemotherapy to 26 months in wildtype KRAS/BRAF patients <75 years in good PS. TMA availability, BRAF mutation and KRAS mutation were all independent prognostic factors for survival. The observed 21% BRAF mutation incidence is higher than the previously and repeatedly reported incidence of 5-12% in mCRC. Screening for BRAF mutations before selection of treatment is relevant for many patients, especially outside clinical trials. A BRAF mutation only partly explained the very poor prognosis of many mCRC patients. Survival in unselected metastatic colorectal cancer patients is extremely variable and subgroups have an extremely short survival compared to trial patients. Patients without available TMA had worse prognostic factors and shorter survival, which questions the total generalizability of present TMA studies and implies that we lack information on the biologically worst mCRC cases. Lack of available tissue is an important underexposed issue which introduces sample bias, and this should be recognized more clearly when conclusions are made from translational mCRC studies.
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| 6755. |
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| 6756. |
- Soriano, Sirena, et al.
(författare)
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Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.
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| 6757. |
- Soriano, Sergi, et al.
(författare)
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Rapid Insulinotropic Action of Low Doses of Bisphenol-A on Mouse and Human Islets of Langerhans: Role of Estrogen Receptor beta
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol-A (BPA) is a widespread endocrine-disrupting chemical (EDC) used as the base compound in the manufacture of polycarbonate plastics. It alters pancreatic beta-cell function and can be considered a risk factor for type 2 diabetes in rodents. Here we used ER beta(-/-) mice to study whether ER beta is involved in the rapid regulation of K-ATP channel activity, calcium signals and insulin release elicited by environmentally relevant doses of BPA (1 nM). We also investigated these effects of BPA in beta-cells and whole islets of Langerhans from humans. 1 nM BPA rapidly decreased K-ATP channel activity, increased glucose-induced [Ca2+](i) signals and insulin release in beta-cells from WT mice but not in cells from ER beta(-/-) mice. The rapid reduction in the K-ATP channel activity and the insulinotropic effect was seen in human cells and islets. BPA actions were stronger in human islets compared to mouse islets when the same BPA concentration was used. Our findings suggest that BPA behaves as a strong estrogen via nuclear ER beta and indicate that results obtained with BPA in mouse beta-cells may be extrapolated to humans. This supports that BPA should be considered as a risk factor for metabolic disorders in humans.
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| 6758. |
- Sorjonen, Kimmo, et al.
(författare)
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Breastfeeding, cognitive ability, and residual confounding : A comment on studies by Pereyra-Elìas et al.
- 2024
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Ingår i: PLOS ONE. - 1932-6203. ; 19:3
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies found positive effects of breastfeeding on the child’s cognitive ability and educational outcomes even when adjusting for maternal cognitive ability in addition to a large number of other potential confounders. The authors claimed an important role of breastfeeding for the child’s cognitive scores. However, it is well known that error in the measurement of confounders can leave room for residual confounding. In the present reanalyses, we found incongruent effects indicating simultaneous increasing and decreasing effects of breastfeeding on the child’s cognitive ability and educational outcomes. We conclude that findings in the reanalyses may have been due to residual confounding due to error in the measurement of maternal cognitive ability. Consequently, it appears premature to assume a genuine increasing effect of breastfeeding on the child’s cognitive ability and educational outcomes and claims in this regard may be challenged.
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| 6759. |
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| 6760. |
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