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| 2. |
- Bivik Stadler, Caroline, 1986-, et al.
(författare)
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Proactive Construction of an Annotated Imaging Database for Artificial Intelligence Training
- 2021
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Ingår i: Journal of digital imaging. - : Springer-Verlag New York. - 0897-1889 .- 1618-727X. ; 34, s. 105-115
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Tidskriftsartikel (refereegranskat)abstract
- Artificial intelligence (AI) holds much promise for enabling highly desired imaging diagnostics improvements. One of the most limiting bottlenecks for the development of useful clinical-grade AI models is the lack of training data. One aspect is the large amount of cases needed and another is the necessity of high-quality ground truth annotation. The aim of the project was to establish and describe the construction of a database with substantial amounts of detail-annotated oncology imaging data from pathology and radiology. A specific objective was to be proactive, that is, to support undefined subsequent AI training across a wide range of tasks, such as detection, quantification, segmentation, and classification, which puts particular focus on the quality and generality of the annotations. The main outcome of this project was the database as such, with a collection of labeled image data from breast, ovary, skin, colon, skeleton, and liver. In addition, this effort also served as an exploration of best practices for further scalability of high-quality image collections, and a main contribution of the study was generic lessons learned regarding how to successfully organize efforts to construct medical imaging databases for AI training, summarized as eight guiding principles covering team, process, and execution aspects.
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| 3. |
- Gustafsson, Jan, et al.
(författare)
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APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom
- 2004
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 101:24, s. 2096-2103
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.
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| 4. |
- Landgren, Filip
(författare)
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An effective three-dimensional de Sitter cosmology in string theory
- 2022
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Ingår i: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479.
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Tidskriftsartikel (refereegranskat)abstract
- Motivated by the lack of consensus on whether or not de Sitter (dS) lies in the Swampland, we use a recently developed braneworld construction and known Anti-de Sitter (AdS) vacua to compute an explicit effective dS cosmology in three dimensions. We consider a non-perturbative AdS(4) vacuum decaying to another lower AdS(4) vacuum via bubble-nucleation. We also consider the more speculative case where a dS(4) decay to a Minkowski(4). The Israel junction conditions are solved across the bubble and we obtain the Friedmann equations from which the cosmological constants can be read off, in the respective cases. The cosmological constants are computed in a flux background yielding small positive values admitting a dS cosmology. However, we find that an energetically viable model in the AdS to AdS case requires more fine-tuning.
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| 5. |
- Omran, Ahmed, et al.
(författare)
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Sclerostin : From Molecule to Clinical Biomarker
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:9
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Forskningsöversikt (refereegranskat)abstract
- Sclerostin, a glycoprotein encoded by the SOST gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling. Osteocytes are differentiated osteoblasts that form a vast and highly complex communication network and orchestrate osteogenesis in response to both mechanical and hormonal cues. The three most commonly described pathways of SOST gene regulation are mechanotransduction, Wnt/beta-catenin, and steroid signaling. Downregulation of SOST and thereby upregulation of local Wnt signaling is required for the osteogenic response to mechanical loading. This review covers recent findings concerning the identification of SOST, in vitro regulation of SOST gene expression, structural and functional properties of sclerostin, pathophysiology, biological variability, and recent assay developments for measuring circulating sclerostin. The three-dimensional structure of human sclerostin was generated with the AlphaFold Protein Structure Database applying a novel deep learning algorithm based on the amino acid sequence. The functional properties of the 3-loop conformation within the tertiary structure of sclerostin and molecular interaction with low-density lipoprotein receptor-related protein 6 (LRP6) are also reviewed. Second-generation immunoassays for intact/biointact sclerostin have recently been developed, which might overcome some of the reported methodological obstacles. Sclerostin assay standardization would be a long-term objective to overcome some of the problems with assay discrepancies. Besides the use of age- and sex-specific reference intervals for sclerostin, it is also pivotal to use assay-specific reference intervals since available immunoassays vary widely in their methodological characteristics.
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| 6. |
- Raffetti, Elena, et al.
(författare)
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Cortisol Concentration as Predictor of Tobacco Initiation in Adolescents: Results From a Population-Based Swedish Cohort
- 2021
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Ingår i: Journal of Adolescent Health. - : Elsevier BV. - 1054-139X. ; 68:4, s. 758-764
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Stress potentiates the smoking reward, decreases the ability to resist smoking, and increases the risk of smoking relapse in adulthood. This study aimed to clarify if salivary cortisol, as an indicator of stress, may be prospectively associated with the onset and phenotype of tobacco use in adolescents. Methods This study was based on a cohort of Swedish adolescents, among whom saliva specimens were collected from a nested sample. We included adolescents with salivary cortisol measurements and without a history of tobacco use (n = 381, aged 13–14 years). Quartiles of morning and afternoon cortisol concentration and cortisol area under the curve were considered as predictors. We categorized tobacco use according to the product mainly used: cigarette smoking, snus use, or either type of tobacco. For each product use, two outcomes were considered: initiation and duration of use. Poisson regression models were used to calculate rate ratios. Results A quartile increase in morning cortisol levels and cortisol area under the curve was consistently associated with a 1.2- to 1.4-fold increased risk of initiation of cigarette smoking snus use, or any tobacco use. Similar results were obtained examining the dose–response relationship and using the duration of use as outcome. No associations were apparent between afternoon cortisol concentration and any of the outcomes. All associations were similar between sexes. Conclusions Morning cortisol concentration, an indicator of hypothalamic–pituitary–adrenal axis activation, is prospectively associated with tobacco use in adolescents. Whether this activation indicates the cumulative effect of stressors during the life course remains to be elucidated.
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| 7. |
- Raffetti, Elena, et al.
(författare)
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DNA methylation of the glucocorticoid receptor gene predicts substance use in adolescence: longitudinal data from over 1000 young individuals.
- 2021
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Early life stress has been linked to increased methylation of the Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene, which codes for the glucocorticoid receptor. Moreover, early life stress has been associated with substance use initiation at a younger age, a risk factor for developing substance use disorders. However, no studies to date have investigated whether NR3C1 methylation can predict substance use in young individuals. This study included adolescents 13-14 years of age that reported no history of substance use at baseline, (N=1041; males=46%). Participants contributed saliva DNA samples and were followed in middle adolescence as part of KUPOL, a prospective cohort study of 7th-grade students in Sweden. Outcome variables were self-reports of (i) recent use, (ii) lifetime use, and (iii) use duration of (a) alcohol, (b) tobacco products, (c) cannabis, or (d) any substance. Outcomes were measured annually for three consecutive years. The predictor variable was DNA methylation at the exon 1F locus of NR3C1. Risk and rate ratios were calculated as measures of association, with or without adjustment for internalizing symptoms and parental psychiatric disorders. For a subset of individuals (N=320), there were also morning and afternoon salivary cortisol measurements available that were analyzed in relation to NR3C1 methylation levels. Baseline NR3C1 hypermethylation associated with future self-reports of recent use and use duration of any substance, before and after adjustment for potential confounders. The overall estimates were attenuated when considering lifetime use. Sex-stratified analyses revealed the strongest association for cigarette use in males. Cortisol analyses revealed associations between NR3C1 methylation and morning cortisol levels. Findings from this study suggest that saliva NR3C1 hypermethylation can predict substance use in middle adolescence. Additional longitudinal studies are warranted to confirm these findings.
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| 8. |
- Sköldberg, Filip, et al.
(författare)
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Identification of AHNAK as a novel autoantigen in systemic lupus erythematosus.
- 2002
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 291:4, s. 951-8
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Tidskriftsartikel (refereegranskat)abstract
- To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18/61) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease.
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| 9. |
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| 10. |
- Sköldberg, Filip
(författare)
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Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.
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