| 1. |
- Brinck, Jonas, et al.
(author)
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E78.0A – en unik, ny ICD-10-kod för familjär hyperkolesterolemi [Sweden introduces a new specific ICD-10 code for the disease familial hypercholesterolemia]
- 2019
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In: Läkartidningen. - Stockholm, Sweden : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116
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Journal article (peer-reviewed)abstract
- At the turn of the year 2018/19, a new ICD-10 code (E78.0A) will be introduced in Sweden for the hereditary blood lipid disorder familial hypercholesterolemia (FH). Patients with FH have a significantly increased risk of developing atherosclerotic disease, such as myocardial infarction before the age of 50. However, early diagnosis and start of treatment of FH can ameliorate the diseases negative long term effects. The Swedish National Board of Health and Welfare gave in its guidelines from 2015 a high priority to the work of identifying and diagnosing individuals with FH in the general population. The introduction of the ICD-10 code E78.0A for FH may, when properly used, be an effective tool in this work.
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| 2. |
- Brinck, Jonas, et al.
(author)
-
[Sweden introduces a new specific ICD-10 code for the disease familial hypercholesterolemia].
- 2019
-
In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 116
-
Journal article (peer-reviewed)abstract
- At the turn of the year 2018/19, a new ICD-10 code (E78.0A) will be introduced in Sweden for the hereditary blood lipid disorder familial hypercholesterolemia (FH). Patients with FH have a significantly increased risk of developing atherosclerotic disease, such as myocardial infarction before the age of 50. However, early diagnosis and start of treatment of FH can ameliorate the disease's negative long term effects. The Swedish National Board of Health and Welfare gave in its guidelines from 2015 a high priority to the work of identifying and diagnosing individuals with FH in the general population. The introduction of the ICD-10 code E78.0A for FH may, when properly used, be an effective tool in this work.
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| 3. |
- Elfstrom, K. Miriam, et al.
(author)
-
Differences in risk for SARS-CoV-2 infection among healthcare workers
- 2021
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In: Preventive Medicine Reports. - : Elsevier BV. - 2211-3355. ; 24
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Journal article (peer-reviewed)abstract
- Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n = 15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n = 12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.
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| 4. |
- Hagey, Daniel W., et al.
(author)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Journal article (peer-reviewed)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 5. |
- Holmberg, Johan, et al.
(author)
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Activation of Neural and Pluripotent Stem Cell Signatures Correlates with Increased Malignancy in Human Glioma
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3, s. e18454-
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Journal article (peer-reviewed)abstract
- The presence of stem cell characteristics in glioma cells raises the possibility that mechanisms promoting the maintenance and self-renewal of tissue specific stem cells have a similar function in tumor cells. Here we characterized human gliomas of various malignancy grades for the expression of stem cell regulatory proteins. We show that cells in high grade glioma co-express an array of markers defining neural stem cells (NSCs) and that these proteins can fulfill similar functions in tumor cells as in NSCs. However, in contrast to NSCs glioma cells co-express neural proteins together with pluripotent stem cell markers, including the transcription factors Oct4, Sox2, Nanog and Klf4. In line with this finding, in high grade gliomas mesodermal-and endodermal-specific transcription factors were detected together with neural proteins, a combination of lineage markers not normally present in the central nervous system. Persistent presence of pluripotent stem cell traits could only be detected in solid tumors, and observations based on in vitro studies and xenograft transplantations in mice imply that this presence is dependent on the combined activity of intrinsic and extrinsic regulatory cues. Together these results demonstrate a general deregulated expression of neural and pluripotent stem cell traits in malignant human gliomas, and indicate that stem cell regulatory factors may provide significant targets for therapeutic strategies.
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| 6. |
- Jiao, Yu, et al.
(author)
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Olfactory ensheathing cells promote neurite outgrowth from co-cultured brain stem slice
- 2011
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In: EXPERIMENTAL NEUROLOGY. - : Elsevier Science B.V., Amsterdam. - 0014-4886 .- 1090-2430. ; 229:1, s. 65-71
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Journal article (peer-reviewed)abstract
- Cell therapy aiming at the replacement of degenerated neurons is a very attractive approach. By using an established in vitro organotypic brain stem (BS) slice culture we screen for candidate donor cells, some of them being further functionally assessed in in vivo models of sensorineural hearing loss. Both in vitro and in vivo systems show that implanted cells face challenges of survival, targeted migration, differentiation and functional integration with the host tissue. Low success rates are possibly due to the lack of necessary neurotrophic factors, adhesion molecules and guiding cues. Olfactory ensheathing cells (OECs) have been shown to express a number of neurotrophic factors and to promote axonal growth through cell to cell interactions. In the present study we co-cultured OECs with organotypic BS slice in order to see if OECs can serve as a facilitator when screening candidate donor cells in an organotypic culture setup. Here we show that OECs when co-cultured with the auditory BS slice not only promote neurite outgrowth from the cochlear nucleus (CN) region of the BS slice but also support cells by having BS slice axons growing along their processes. These findings further suggest that OECs may enhance survival and targeted migration of candidate donor cells suitable for cell therapy in vitro and in vivo. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.
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| 7. |
- Klum, Susanne, et al.
(author)
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Sequentially acting SOX proteins orchestrate astrocyte- and oligodendrocyte-specific gene expression
- 2018
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In: EMBO Reports. - : WILEY. - 1469-221X .- 1469-3178. ; 19:11
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Journal article (peer-reviewed)abstract
- SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, by ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA regions strongly enriched for Nfi binding motifs. Oligodendrocyte genes instead are prebound by SOX9 only, at sites which during oligodendrocyte maturation are targeted by SOX10. Interestingly, reporter gene assays and functional studies in the spinal cord reveal that SOX3 binding represses the synergistic activation of astrocyte genes by SOX9 and NFIA, whereas oligodendrocyte genes are activated in a combinatorial manner by SOX9 and SOX10. These genome-wide studies demonstrate how sequentially expressed SOX proteins act on lineage-specific regulatory DNA elements to coordinate glial gene expression both in a temporal and in a sub-lineage-specific fashion.
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| 8. |
- Kurtsdotter, Idha, et al.
(author)
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SOX5/6/21 prevent oncogene-driven transformation of brain stem cells
- 2017
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:18, s. 4985-4997
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Journal article (peer-reviewed)abstract
- Molecular mechanisms preventing self-renewing brain stem cells from oncogenic transformation are poorly defined. We show that the expression levels of SOX5, SOX6, and SOX21 (SOX5/6/21) transcription factors increase in stem cells of the subventricular zone (SVZ) upon oncogenic stress, whereas their expression in human glioma decreases during malignant progression. Elevated levels of SOX5/6/21 promoted SVZ cells to exit the cell cycle, whereas genetic ablation of SOX5/6/21 dramatically increased the capacity of these cells to form glioma-like tumors in an oncogene-driven mouse brain tumor model. Loss-of-function experiments revealed that SOX5/6/21 prevent detrimental hyperproliferation of oncogene expressing SVZ cells by facilitating an antiproliferative expression profile. Consistently, restoring high levels of SOX5/6/21 in human primary glioblastoma cells enabled expression of CDK inhibitors and decreased p53 protein turnover, which blocked their tumorigenic capacity through cellular senescence and apoptosis. Altogether, these results provide evidence that SOX5/6/21 play a central role in driving a tumor suppressor response in brain stem cells upon oncogenic insult.
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| 9. |
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| 10. |
- Panman, Lia, et al.
(author)
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Sox6 and Otx2 Control the Specification of Substantia Nigra and Ventral Tegmental Area Dopamine Neurons
- 2014
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 8:4, s. 1018-1025
-
Journal article (peer-reviewed)abstract
- Distinct midbrain dopamine (mDA) neuron subtypes are found in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), but it is mainly SNc neurons that degenerate in Parkinson's disease. Interest in how mDA neurons develop has been stimulated by the potential use of stem cells in therapy or disease modeling. However, very little is known about how specific dopaminergic subtypes are generated. Here, we show that the expression profiles of the transcription factors Sox6, Otx2, and Nolz1 define subpopulations of mDA neurons already at the neural progenitor cell stage. After cell-cycle exit, Sox6 selectively localizes to SNc neurons, while Otx2 and Nolz1 are expressed in a subset of VTA neurons. Importantly, Sox6 ablation leads to decreased expression of SNc markers and a corresponding increase in VTA markers, while Otx2 ablation has the opposite effect. Moreover, deletion of Sox6 affects striatal innervation and dopamine levels. We also find reduced Sox6 levels in Parkinson's disease patients. These findings identify Sox6 as a determinant of SNc neuron development and should facilitate the engineering of relevant mDA neurons for cell therapy and disease modeling.
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