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- Börgeson, Emma, et al.
(författare)
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Challenges in PhD education due to COVID-19-disrupted supervision or business as usual: a cross-sectional survey of Swedish biomedical sciences graduate students
- 2021
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background It remains unclear to what extent the SARS-CoV-2/COVID-19 pandemic disrupted the normal progression of biomedical and medical science graduate programs and if there was a lasting impact on the quality and quantity of supervision of PhD-students. To date, multiple editorials and commentaries indicate the severity of the disruption without providing sufficient evidence with quantifiable data. Methods An online survey was submitted to the administrative offices of biomedical and medical PhD-programs at eight major universities in Sweden to gauge the impact of the pandemic on the students. It consisted of multiple-choice and open-ended questions where students could provide examples of positive and/or negative supervision strategies. Open answered questions were coded as either examples of positive or negative support. Results PhD students were divided into two groups: those with improved or unchanged supervision during the pandemic (group 1, n = 185), versus those whose supervision worsened (group 2, n = 69). Group 1 received more help from supervisors and more frequent supervision via both online and alternative platforms (email/messages and telephone). There was no significant difference in educational-stage, gender or caretaking responsibilities between the groups. Conclusions It is important for the scientific community to learn how to provide the best possible supervision for PhD students during the pandemic. Our data suggests that more frequent supervision, and using a diverse array of meeting platforms is helpful. In addition, it is important for the students to feel that they have their supervisor's emotional support. Several students also expressed that they would benefit from an extension of their PhD programs due to delays caused by the pandemic.
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| 2. |
- Franceschini, N., et al.
(författare)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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| 3. |
- Jaworek, T., et al.
(författare)
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Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:16
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
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| 6. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 7. |
- Pedersen, Camilla Christina, et al.
(författare)
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Serum neurofilament light at diagnosis: a prognostic indicator for accelerated disease progression in Parkinson's Disease
- 2024
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Ingår i: NPJ PARKINSONS DISEASE. - 2373-8057. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light chain (NFL) is elevated in neurodegenerative diseases, including Parkinson's disease (PD). This study aimed to investigate serum NFL in newly diagnosed PD and its association with cognitive and motor decline over 10 years. Serum NFL levels were measured in PD patients and controls from the ParkWest study at diagnosis (baseline) and after 3 and 5 years. Mixed-effects regression analyzed changes in NFL and the association with annual changes in MMSE and UPDRS-III scores over 10 years. PD patients had elevated serum NFL at all visits and a faster annual increase over 5 years compared to controls (0.09 pg/mL per year; p = 0.029). Higher baseline NFL predicted faster cognitive decline beta -0.77 transformed MMSE; p = 0.010), and a 40% NFL increase predicted future motor decline (beta 0.28 UPDRS-III; p = 0.004). Elevated serum NFL in early PD is linked to faster cognitive and motor impairment, suggesting its prognostic value in PD biomarker panels.
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| 8. |
- Rohin Rajan, Meenu, et al.
(författare)
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Comparative analysis of obesity-related cardiometabolic and renal biomarkers in human plasma and serum.
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The search for biomarkers associated with obesity-related diseases is ongoing, but it is not clear whether plasma and serum can be used interchangeably in this process. Here we used high-throughput screening to analyze 358 proteins and 76 lipids, selected because of their relevance to obesity-associated diseases, in plasma and serum from age- and sex-matched lean and obese humans. Most of the proteins/lipids had similar concentrations in plasma and serum, but a subset showed significant differences. Notably, a key marker of cardiovascular disease PAI-1 showed a difference in concentration between the obese and lean groups only in plasma. Furthermore, some biomarkers showed poor correlations between plasma and serum, including PCSK9, an important regulator of cholesterol homeostasis. Collectively, our results show that the choice of biofluid may impact study outcome when screening for obesity-related biomarkers and we identify several markers where this will be the case.
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| 9. |
- Silfverberg, Thomas, et al.
(författare)
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Haematopoietic stem cell transplantation for treatment of relapsing-remitting multiple sclerosis in Sweden: an observational cohort study
- 2023
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA growing evidence base supports the use of autologous haematopoietic stem cell transplantation (aHSCT) for treatment of relapsing-remitting multiple sclerosis (RRMS), but it has not yet been integrated into most national clinical guidelines. The objective of this study was to assess efficacy and safety when aHSCT is implemented in routine healthcare.MethodsWe assessed 231 patients and the final analysis included 174 RRMS patients who were treated with aHSCT in Sweden before 1 January 2020. Efficacy was evaluated by performing a retrospective analysis of prospectively collected data from the Swedish MS registry. Procedure-related safety was assessed by analysing data from electronic patient records covering a period of 100 days following aHSCT.ResultsWith a median follow-up time of 5.5 (IQR: 3.4-7.5) years, the Kaplan-Meier estimate for no evidence of disease activity was 73% (95% CI 66% to 81%) at 5 years and 65% (95% CI 57% to 75%) at 10 years. Out of the 149 patients with baseline disability, 80 (54%) improved, 55 (37%) were stable and 14 (9%) deteriorated. The mean number of adverse events per patient was 1.7 (& PLUSMN;SD: 1.5) for grade 3 events and 0.06 (& PLUSMN;SD: 0.3) for grade 4 events. Febrile neutropenia was the most common adverse event, affecting 68% of patients. There was no treatment-related mortality.ConclusionsTreatment with aHSCT for RRMS is associated with freedom from disease activity in a majority of patients, with acceptable adverse events. This procedure should be considered a standard of care for patients with highly active RRMS.
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| 10. |
- Sotak, Matus, et al.
(författare)
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Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects againstobesity-inducedsystemic disease inmice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularlywell to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generatingenzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
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