| 1. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 2. |
- Asp, Michaela, et al.
(författare)
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Spatial detection of fetal marker genes expressed at low level in adult human heart tissue
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.
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| 3. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 4. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 5. |
- Das, Sarbashis, et al.
(författare)
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Transcriptomics of cardiac biopsies reveals differences in patients with or without diagnostic parameters for heart failure with preserved ejection fraction
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure affects 2-3% of adult Western population. Prevalence of heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) increases. Studies suggest HFpEF patients to have altered myocardial structure and functional changes such as incomplete relaxation and increased cardiac stiffness. We hypothesised that patients undergoing elective coronary bypass surgery (CABG) with HFpEF characteristics would show distinctive gene expression compared to patients with normal LV physiology. Myocardial biopsies for mRNA expression analysis were obtained from sixteen patients with LV ejection fraction >= 45%. Five out of 16 patients (31%) had echocardiographic characteristics and increased NTproBNP levels indicative of HFpEF and this group was used as HFpEF proxy, while 11 patients had Normal LV physiology. Utilising principal component analysis, the gene expression data clustered into two groups, corresponding to HFpEF proxy and Normal physiology, and 743 differentially expressed genes were identified. The associated top biological functions were cardiac muscle contraction, oxidative phosphorylation, cellular remodelling and matrix organisation. Our results also indicate that upstream regulatory events, including inhibition of transcription factors STAT4, SRF and TP53, and activation of transcription repressors HEY2 and KDM5A, could provide explanatory mechanisms to observed gene expression differences and ultimately cardiac dysfunction in the HFpEF proxy group.
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| 6. |
- Landberg, Göran, 1963, et al.
(författare)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 7. |
- Landberg, Göran, et al.
(författare)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
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Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 8. |
- Linde, C., et al.
(författare)
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Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study : an epidemiological regional study in Stockholm county of 2.1 million inhabitants
- 2016
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Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 18:10, s. 1287-1297
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF ( https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Methods: Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. Conclusions: In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF.
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| 9. |
- Malm, Joakim, et al.
(författare)
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UTVÄRDERING AV SI-VERKSAMHETEN VID LUNDS UNIVERSITET 2016/17
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Samverkansinlärning/Supplemental Instruction (SI) är en pedagogisk metod som syftar till att öka genomströmningen i svåra kurser. Metoden uppstod i USA vid University of Missouri Kansas City i mitten på 1970-talet och har därefter spridits till mer än 1500 högre lärosäten i ett trettiotal länder (Martin, 2008). Kort kan SI sägas vara ett studentdrivet komplement till ordinarie undervisning vid högre utbildning. Material i en kurs bearbetas tillsammans i en studiegrupp genom diskussion och grupparbeten under ledning av en äldre student – den s.k. SI-ledaren. Samverkansinlärning kom till Lunds universitet 1994 och har fått stor spridning på universitetet. Lund universitet utgör också ett nav för SI både i Sverige (SI finns på ca 15 svenska högre lärosäten) och i Europa och är också platsen för det nordeuropeiska SI-centret som ansvarar för utbildning och uppföljning i området på uppdrag av det internationella SI-centret i USA. Denna rapport sammanfattar resultaten från en utvärdering av SI-verksamheten vid Lunds universitet under läsåret 2016/17. SI-programmet vid Lunds universitet är omfattande med verksamhet på sex av universitetets fakulteter. Totalt har vi årligen ca 230 verksamma SIledare i ett sjuttiotal kurser. Organisationen av SI varierar mellan de olika fakulteterna. En ytterlighet finns vid LTH och naturvetenskaplig fakultet där verksamheten är starkt centraliserad. Den andra ytterligheten är vid samhällsvetenskaplig fakultet där SI-verksamheten är decentraliserad till de olika ämnena. Det som förenar de olika verksamhetsansvariga är den entusiasm som finns för SI-konceptet samt de dedikerade studenter som är SI-ledare. Närvaron på SI-möten är relativt god. Totalt har vi över 4000 studenter vid Lunds universitet som nyttjar SI varje år och en närvaro kring 30 % av kursregistrerade i snitt. Antalet deltagare på ett SI-möte ligger kring 10 i medeltal med en standardavvikelse kring 5 studenter, vilket ger goda förutsättningar för produktiva SI-möten generellt sett. De utvärderingar som gjorts av sambandet mellan SI-närvaro och kursresultat antyder att aktivt deltagande på SI ökar chanserna till ett bra resultat på kursen oavsett ämne. En specialundersökning i en kurs i matematik antyder också att alla studenter verkar gynnas av att gå på SI oavsett förkunskapsnivå. Enkätutvärderingar bland deltagarna antyder att den främsta drivkraften att delta på SI är att förstå kursmaterialet oavsett ämne och fakultet. Strategiska motiv som att klara kursen är normalt underordnade även om detta varierar beroende på fakultet/ämne. Det är roligt att konstatera att studiesocial interaktion mestadels värderas högt som motiv att delta på SI. Arbetsmiljön på SI upplevs som bra (lätt att fråga, lättsam, positiv och stödjande atmosfär samt lagom tempo) och generellt verkar mötena följa SI-metodiken väl. Oavsett fakultet verkar majoriteten av deltagarna känna att SI-mötena hjälper dem i deras kursarbete. De får en bättre förståelse av vad som förväntas av dem i kursen, ett ökat intresse för ämnet samt stöd i kursarbetet. De allra flesta verkar känna att de får en betydligt djupare förståelse för det kursmaterial man går igenom på SI-mötena. Dessutom upplever många att de sannolikt kommer att förbättra sitt kursresultat genom deltagande på SI. Detta antagande stödjs också som nämnts ovan av SI-närvaro och examinationsstatistik från kurser och ju högre SI närvaro desto bättre verkar det gå oavsett ämnesområde. Att döma av deltagarnas enkätsvar är det inte bara kursen med tillhörande SI som gynnas av SI-deltagande. Flera generella färdigheter tränas som bör gynna studenter i studier i andra kurser utan SI. Många deltagare upplever att färdigheter som problemlösningsförmåga, kritiskt tänkande, lagsamverkan och samarbete, presentation inför andra och sätt att studera utvecklats genom att delta på SI. Dessutom får flera ett förbättrat självförtroende i sina studier samt ett ökat nätverk av studiekamrater. Tidigare studier vid LTH antyder att de som deltagit på SI också presterar bättre i andra kurser utan SI och att de är mindre benägna att göra studieavbrott och tar ut examen i högre utsträckning (Malm, Bryngfors, & Mörner, 2012; Malm, Bryngfors, & Mörner, 2015; Malm, Bryngfors, & Fredriksson, 2017). Deltagarnas svar på frågan med ”Vad tycker du är det bästa med SI-mötena?” betonar möjligheten till diskussion och social interaktion, en god studiemiljö samt förståelseinriktad studietid. Detta gäller oavsett ämnesområde. Vad kan då förbättras med SI-mötena? Några antyder att strukturen/effektiviteten på mötena kan vara bristande. Detta kan i sin tur bero av att stödet för SI-ledare i form av observationer och handledning inte alltid fungerar som det skall. Detta är något att titta närmare på inom universitetet. Annat som kan förbättras med SI-verksamheten är att man vill ha fler möten, mer tid till mötena eller bättre schematider. Internationellt anses det ofta att SI-ledarna är de största ”vinnarna” i SI-konceptet pga de ledarskaps- och grupphanteringsfärdigheter de erhåller. Detta antyds även i enkätutvärderingarna för SI-ledare vid Lunds universitet. SI-ledarna verkar dessutom få ett bättre självförtroende, djupare förståelse av kursämnet samt bli bättre på att prata inför andra. Både deltagare och SI-ledare är generellt nöjda med sina möten.
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| 10. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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