| 1. |
- Borgmästars, Emmy, et al.
(författare)
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Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
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| 2. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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| 3. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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| 4. |
- Hendry, Alexandra, et al.
(författare)
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Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
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Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
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Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
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| 5. |
- Holmberg, Jonas, 1976-, et al.
(författare)
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Influence of Local Electropolishing Conditions on Ferritic–Pearlitic Steel on X-Ray Diffraction Residual Stress Profiling
- 2024
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Ingår i: Journal of materials engineering and performance (Print). - : Springer. - 1059-9495 .- 1544-1024. ; 33, s. 3682-
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Tidskriftsartikel (refereegranskat)abstract
- Layer removal with electropolishing is a well-established method when measuring residual stress profiles with lab-XRD. This is done to measure the depth impact from processes such as shot peening, heat treatment, or machining. Electropolishing is used to minimize the influence on the inherent residual stresses of the material during layer removal, performed successively in incremental steps to specific depths followed by measurement. Great control of the material removal is critical for the measured stresses at each depth. Therefore, the selection of size of the measurement spot and electropolishing parameters is essential. The main objective in this work is to investigate how different electrolytes and electropolishing equipment affect the resulting surface roughness, geometry, microstructure, and consequently the measured residual stress. A second objective has been to establish a methodology of assessing the acquired electropolished depth. The aim has been to get a better understanding of the influence of the layer removal method on the accuracy of the acquired depth. Evaluation has been done by electropolishing one ground and one shot peened sample of a low-alloy carbon steel, grade 1.1730, with different methods. The results showed a difference in stresses depending on the electrolyte used where the perchloric acid had better ability to retain the stresses compared to the saturated salt. Electropolishing with saturated salt is fast and results in evenly distributed material removal but has high surface roughness, which is due to a difference in electropolishing of the two phases, ferrite, and pearlite. Perchloric acid electropolishing is slower but generates a smooth surface as both ferrite and pearlite have the same material removal rates but may cause an increased material removal for the center of the electropolished area. In this work, it is suggested to use perchloric acid electropolishing for the final layer removal step. © 2023, The Author(s).
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| 6. |
- Holmgren, Klas, et al.
(författare)
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Preoperative biomarkers related to inflammation may identify high-risk anastomoses in colorectal cancer surgery : explorative study
- 2022
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal anastomotic leakage can be considered a process of failed wound healing, for which related biomarkers might be a promising research area to decrease leak rates.METHODS: Patients who had elective surgery with a primary anastomosis for non-metastatic colorectal cancer, at two university hospitals between 1 January 2010 and 31 December 2015 were included. Patients with an anastomotic leak were identified and matched (1:1) to complication-free controls on the basis of sex, age, tumour stage, tumour location, and operating hospital. Preoperative blood samples were analysed by use of protein panels associated with systemic or enteric inflammation by proteomics, and enzyme-linked immunosorbent assays. Multivariable projection methods were used in the statistical analyses and adjusted for multiple comparisons to reduce false positivity. Rectal cancer tissue samples were evaluated with immunohistochemistry to determine local expression of biomarkers that differed significantly between cases and controls.RESULTS: Out of 726 patients undergoing resection, 41 patients with anastomotic leakage were matched to 41 controls. Patients with rectal cancer with leakage displayed significantly elevated serum levels of 15 proteins related to inflammation. After controlling for a false discovery rate, levels of C-X-C motif chemokine 6 (CXCL6) and C-C motif chemokine 11 (CCL11) remained significant. In patients with colonic cancer with leakage, levels of high-sensitivity C-reactive protein (hs-CRP) were increased before surgery. Local expression of CXCL6 and CCL11, and their receptors, were similar in rectal tissues between cases and controls.CONCLUSION: Patients with anastomotic leakage could have an upregulated inflammatory response before surgery, as expressed by elevated serological levels of CXCL6 and CCL11 for rectal cancer and hs-CRP levels in patients with colonic cancer respectively.
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| 7. |
- Li, Baojing, et al.
(författare)
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Educational level and the risk of mental disorders, substance use disorders and self-harm in different age-groups : A cohort study covering 1,6 million subjects in the Stockholm region
- 2023
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Ingår i: International Journal of Methods in Psychiatric Research. - : Wiley. - 1049-8931 .- 1557-0657. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations between low education and risk of mental disorders, substance use disorders and self-harm in different age-groups.Methods: All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed-up for these disorders in health care registers 2001–2016. Subjects were stratified into four age-groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models.Results: Low education increased the risk of substance use disorders and self-harm in all age-groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism.Conclusion: Low education is associated with risk of most mental disorders, substance use disorders and self-harm in all age-groups, but especially among those aged 28–50 years.
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| 8. |
- Lindgren, Moa, et al.
(författare)
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Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:14
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Tidskriftsartikel (refereegranskat)abstract
- Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
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| 9. |
- Lundin, Martin, 1975-, et al.
(författare)
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Leadership Experiences, Labor Market Entry, and Early Career Trajectories
- 2021
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Ingår i: The Journal of human resources. - : University of Wisconsin Press. - 0022-166X .- 1548-8004. ; 56:2, s. 480-511
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Tidskriftsartikel (refereegranskat)abstract
- Matching archive data on election discontinuities to register data on labor market trajectories, we estimate the causal effects of being elected into Swedish student union councils on subsequent labor market careers. Marginally elected students are much more likely to have a rapid transition into employment. Effects are not confined to establishments, organizations, or industries where previous candidates are employed, suggesting that the benefits are general in nature. Elected representatives have higher labor earnings within three years, but not thereafter. Overall, leadership experiences before labor market entry boost individuals' early careers, whereas mid-term outcomes are unaffected.
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| 10. |
- Mason, James E., et al.
(författare)
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A cross-sectional and longitudinal analysis of pre-diagnostic blood plasma biomarkers for early detection of pancreatic cancer
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:21
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.
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