| 1. |
- Eriksson, Victoria, et al.
(författare)
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Thromboembolic events during neoadjuvant chemotherapy in muscle invasive bladder cancer – any correlation to the central venous access? : A clinical practice article
- 2022
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Ingår i: F1000 Research. - : F1000 Research. - 2046-1402. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Patients with muscle invasive bladder cancer have a generally known 5-year overall survival of approximately 58% with neoadjuvant chemotherapy (NAC). During the last decades, addition of Cisplatinum-based NAC in fit patients prior to radical cystectomy (RC), has significantly improved OS, compared to RC only. However, some published studies following NAC addition, describe an intermediate risk increase of thromboembolic events (TEEs). Placement of central venous access (CVA) before NAC has also been suggested as being a potential risk factor for thrombosis. We present a combination of images and cases from the Northern Swedish health region where three patients developed venous TEE after CVA placement for NAC-administration and found that the time until curable RC was prolonged circa one month each, with an addition of one RC cancelled. These are serious events and to our knowledge, there are no current guidelines on prevention of TEE before RC. The aim with this report was to provide examples of these events and conclude that further prospective trials are warranted on prevention and future guidelines regarding venous anticoagulant treatment for TEE that occur pre-RC in NAC-patients.
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| 2. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 3. |
- Wiberg, Erik, et al.
(författare)
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A validation study of cT-categories in the Swedish national urinary bladder cancer register - Norrland University Hospital
- 2023
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive.METHODS: The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model.RESULTS: cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009-2012.CONCLUSION: The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification.
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| 4. |
- Arvidsson, Sandra, 1986-, et al.
(författare)
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Enlarged cross-sectional area in peripheral nerves in Swedish patients with hereditary V30M transthyretin amyloidosis
- 2023
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Ingår i: Annals of Medicine. - : Taylor & Francis Group. - 0785-3890 .- 1365-2060. ; 55:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In hereditary transthyretin amyloidosis (ATTRv), two different fibrillar forms causing the amyloid deposition, have been identified, displaying substantially cardiac or neuropathic symptoms. Neuropathic symptoms are more frequent in early-onset patients, whereas late-onset patients, besides cardiac symptoms, seem to develop carpal tunnel syndrome, more often. With ultrasonography (US) of peripheral nerves, it is possible to distinguish structural changes, and enlarged cross-sectional area (CSA). The main purpose of this study was, for the first time, to elucidate US of peripheral nerves in Swedish ATTRv patients at an early stage of the disease, and to evaluate possible early enlarged CSA.Material and methods: This prospective study included first visit data of 13 patients, aged 30–88 years, of which 11 with late-onset age. All had a positive V30M mutation. Eight men and six women (aged 28–74 years) served as controls.Results: Significantly enlarged CSA was seen in ATTRv patients for the tibial nerve at the ankle (p =.001), the sural nerve (p <.001), the peroneal nerve at the popliteal fossa (p =.003), and the ulnar nerve at the middle upper arm (p =.007).Conclusion: US of peripheral nerves could be a valuable tool in disease evaluation and could facilitate monitoring of disease progression.
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| 5. |
- Banks, Victoria A., et al.
(författare)
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Is partially automated driving a bad idea? : Observations from an on-road study
- 2018
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Ingår i: Applied Ergonomics. - : Elsevier Ltd. - 0003-6870 .- 1872-9126. ; 68, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- The automation of longitudinal and lateral control has enabled drivers to become “hands and feet free” but they are required to remain in an active monitoring state with a requirement to resume manual control if required. This represents the single largest allocation of system function problem with vehicle automation as the literature suggests that humans are notoriously inefficient at completing prolonged monitoring tasks. To further explore whether partially automated driving solutions can appropriately support the driver in completing their new monitoring role, video observations were collected as part of an on-road study using a Tesla Model S being operated in Autopilot mode. A thematic analysis of video data suggests that drivers are not being properly supported in adhering to their new monitoring responsibilities and instead demonstrate behaviour indicative of complacency and over-trust. These attributes may encourage drivers to take more risks whilst out on the road. © 2017 Elsevier Ltd
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| 6. |
- Blom, Victoria, et al.
(författare)
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Lifestyle Habits and Mental Health in Light of the Two COVID-19 Pandemic Waves in Sweden, 2020
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 18:6
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has become a public health emergency of international concern, which may have affected lifestyle habits and mental health. Based on national health profile assessments, this study investigated perceived changes of lifestyle habits in response to the COVID-19 pandemic and associations between perceived lifestyle changes and mental health in Swedish working adults. Among 5599 individuals (50% women, 46.3 years), the majority reported no change (sitting 77%, daily physical activity 71%, exercise 69%, diet 87%, alcohol 90%, and smoking 97%) due to the pandemic. Changes were more pronounced during the first wave (April-June) compared to the second (October-December). Women, individuals <60 years, those with a university degree, white-collar workers, and those with unhealthy lifestyle habits at baseline had higher odds of changing lifestyle habits compared to their counterparts. Negative changes in lifestyle habits and more time in a mentally passive state sitting at home were associated with higher odds of mental ill-health (including health anxiety regarding one's own and relatives' health, generalized anxiety and depression symptoms, and concerns regarding employment and economy). The results emphasize the need to support healthy lifestyle habits to strengthen the resilience in vulnerable groups of individuals to future viral pandemics and prevent health inequalities in society.
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| 7. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 8. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 9. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 10. |
- Demchev, Denis, 1984, et al.
(författare)
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Improving Sea Ice Drift Retrieval from SAR Images Using Phase- and Cross-Correlation Techniques
- 2020
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Ingår i: Proceedings of the 2020 IEEE Conference of Russian Young Researchers in Electrical and Electronic Engineering, EIConRus 2020. ; , s. 1378-1381
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Konferensbidrag (refereegranskat)abstract
- A new combination of phase- and cross-correlation techniques for sea ice tracking from sequential synthetic aperture radar images investigated. An operational Python-based sea ice drift algorithm based on this combination from Sentinel-1 images is proposed.
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