| 1. |
- Almroth, Melody, 1989-, et al.
(författare)
-
The role of working conditions in educational differences in all-cause and ischemic heart disease mortality among Swedish men
- 2024
-
Ingår i: Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 50:4, s. 300-309
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aims to investigate the extent to which low job control and heavy physical workload in middle age explain educational differences in all-cause and ischemic heart disease (IHD) mortality while accounting for important confounding factors.Methods The study is based on a register-linked cohort of men who were conscripted into the Swedish military at around the age of 18 in 1969/1970 and were alive and registered in Sweden in 2005 (N=46 565). Cox proportional hazards regression models were built to estimate educational differences in all-cause and IHD mortality and the extent to which this was explained by physical workload and job control around age 55 by calculating the reduction in hazard ratio (HR) after adjustments. Indicators of health, health behavior, and other factors measured during conscription were accounted for.Results We found a clear educational gradient for all-cause and IHD mortality (HR 2.07 and 2.47, respectively, for the lowest compared to the highest education level). A substantial part was explained by the differential distribution of the confounding factors. However, work-related factors, especially high physical workload, also played important explanatory roles.Conclusion Even after accounting for earlier life factors, low job control and especially high physical workload seem to be important mechanistic factors in explaining educational inequalities in all-cause and IHD mortality. It is therefore important to find ways to reduce physical workload and increase job control in order to decrease inequalities in mortality.
|
|
| 2. |
|
|
| 3. |
- Berglund, Emelie, et al.
(författare)
-
Automation of Spatial Transcriptomics library preparation to enable rapid and robust insights into spatial organization of tissues
- 2020
-
Ingår i: BMC Genomics. - : Springer Nature. - 1471-2164. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Interest in studying the spatial distribution of gene expression in tissues is rapidly increasing. Spatial Transcriptomics is a novel sequencing-based technology that generates high-throughput information on the distribution, heterogeneity and co-expression of cells in tissues. Unfortunately, manual preparation of high-quality sequencing libraries is time-consuming and subject to technical variability due to human error during manual pipetting, which results in sample swapping and the accidental introduction of batch effects. All these factors complicate the production and interpretation of biological datasets.Results: We have integrated an Agilent Bravo Automated Liquid Handling Platform into the Spatial Transcriptomics workflow. Compared to the previously reported Magnatrix 8000+ automated protocol, this approach increases the number of samples processed per run, reduces sample preparation time by 35%, and minimizes batch effects between samples. The new approach is also shown to be highly accurate and almost completely free from technical variability between prepared samples.Conclusions: The new automated Spatial Transcriptomics protocol using the Agilent Bravo Automated Liquid Handling Platform rapidly generates high-quality Spatial Transcriptomics libraries. Given the wide use of the Agilent Bravo Automated Liquid Handling Platform in research laboratories and facilities, this will allow many researchers to quickly create robust Spatial Transcriptomics libraries.
|
|
| 4. |
- Berglund, Emelie
(författare)
-
Molecular and Spatial Profiling of Prostate Tumors
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every cancer tumor is unique, with characteristics that change over time. The evolution of a full-blown malignancy from a single cell that gives rise to a heterogeneous population of cancer cells is a complex process. The use of spatial information makes a big contribution to understanding the progression of tumors and how patients respond to treatment. Currently, the scientific community is taking a step further in order to understand gene expression heterogeneity in the context of tissue spatial organization to shed light on cell- to-cell interactions. Technological advances in recent years have increased the resolution at which heterogeneity can be observed. Spatial transcriptomics (ST) is an in situ capturing technique that uses a glass slide containing oligonucleotides to capture mRNAs while maintaining the spatial information of histological tissue sections. It combines histology and Illumina sequencing to detect and visualize the whole transcriptome information of tissue sections. In Paper I, an AI method was developed to create a computerized tissue anatomy. The rich source of information enables the AI method to identify genetic patterns that cannot be seen by the naked eye. This study also provided insights into gene expression in the environment surrounding the tumor, the tumor microenvironment, which interacts with tumor cells for cancer growth and progression. In Paper II, we investigate the cellular response of treatment. It is well known that virtually all patients with hormone naïve prostate cancer treated with GnRH agonists will relapse over time and that the cancer will transform into a castration-resistant form denoted castration-resistant prostate cancer. This study shows that by characterizing the non-responding cell populations, it may be possible to find an alternative way to target them in the early stages and thereby decrease the risk of relapse. In Paper III, we deal with scalability limitations, which in the ST method are represented by time- consuming workflow in the library preparation. This study introduces an automated library preparation protocol on the Agilent Bravo Automated Liquid Handling Platform to enable rapid and robust preparation of ST libraries. Finally, Paper IV expands on the first work and illustrates the utility of the ST technology by constructing, for the first time, a molecular view of a cross-section of a prostate organ.
|
|
| 5. |
- Berglund, Emelie, et al.
(författare)
-
Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
|
|
| 6. |
- Borgström, Erik, et al.
(författare)
-
Phasing of single DNA molecules by massively parallel barcoding
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing platforms mainly produce short-read data, resulting in a loss of phasing information for many of the genetic variants analysed. For certain applications, it is vital to know which variant alleles are connected to each individual DNA molecule. Here we demonstrate a method for massively parallel barcoding and phasing of single DNA molecules. First, a primer library with millions of uniquely barcoded beads is generated. When compartmentalized with single DNA molecules, the beads can be used to amplify and tag any target sequences of interest, enabling coupling of the biological information from multiple loci. We apply the assay to bacterial 16S sequencing and up to 94% of the hypothesized phasing events are shown to originate from single molecules. The method enables use of widely available short-read-sequencing platforms to study long single molecules within a complex sample, without losing phase information.
|
|
| 7. |
- Erickson, A, et al.
(författare)
-
Spatially resolved clonal copy number alterations in benign and malignant tissue
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 608:7922, s. 360-
-
Tidskriftsartikel (refereegranskat)abstract
- Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
|
|
| 8. |
|
|
| 9. |
- Erickson, Andrew, et al.
(författare)
-
The spatial landscape of clonal somatic mutations in benign and malignant tissue
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
|
|
| 10. |
|
|
