| 1. |
- Hedegaard, Jakob, et al.
(author)
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Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
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Journal article (peer-reviewed)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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| 2. |
- Nielsen, Jakob Toudahl, et al.
(author)
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In situ high-resolution structure of the baseplate antenna complex in Chlorobaculum tepidum.
- 2016
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In: Nature Communications. - : Springer Science+Business Media B.V.. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Photosynthetic antenna systems enable organisms harvesting light and transfer the energy to the photosynthetic reaction centre, where the conversion to chemical energy takes place. One of the most complex antenna systems, the chlorosome, found in the photosynthetic green sulfur bacterium Chlorobaculum (Cba.) tepidum contains a baseplate, which is a scaffolding super-structure, formed by the protein CsmA and bacteriochlorophyll a. Here we present the first high-resolution structure of the CsmA baseplate using intact fully functional, light-harvesting organelles from Cba. tepidum, following a hybrid approach combining five complementary methods: solid-state NMR spectroscopy, cryo-electron microscopy, isotropic and anisotropic circular dichroism and linear dichroism. The structure calculation was facilitated through development of new software, GASyCS for efficient geometry optimization of highly symmetric oligomeric structures. We show that the baseplate is composed of rods of repeated dimers of the strongly amphipathic CsmA with pigments sandwiched within the dimer at the hydrophobic side of the helix.
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| 3. |
- Björkman, Anders, et al.
(author)
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Distal Scaphoid Fractures
- 2017
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In: Scaphoid Fractures : Evidence-Based Management - Evidence-Based Management. - 9780323485647 - 9780323496056 ; , s. 123-128
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Book chapter (peer-reviewed)
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| 4. |
- Chattopadhyay, Subhayan, et al.
(author)
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Enrichment of B cell receptor signaling and epidermal growth factor receptor pathways in monoclonal gammopathy of undetermined significance : a genome-wide genetic interaction study
- 2018
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In: Molecular Medicine. - : Springer Science and Business Media LLC. - 1528-3658 .- 1076-1551. ; 24:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways.METHODS: Polygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls). Further investigation on gene-set enrichment, regulatory pathway and genetic network was carried out with stand-alone in silico tools separately for both interaction and genome-wide association study-detected risk loci.RESULTS: Intronic-PREX1 (20q13.13), a reported locus predisposing to MM was confirmed to have contribution to excess MGUS risk in interaction with SETBP1, a well-established candidate predisposing to myeloid malignancies. Pathway enrichment showed B cell receptor signaling pathway (P < 5.3 × 10- 3) downstream to allograft rejection pathway (P < 5.6 × 10- 4) and autoimmune thyroid disease pathway (P < 9.3 × 10- 4) as well as epidermal growth factor receptor regulation pathway (P < 2.4 × 10- 2) to be differentially regulated. Oncogene ALK and CDH2 were also identified to be moderately interacting with rs10251201 and rs16966921, two previously reported risk loci for MGUS.CONCLUSIONS: We described novel pathways and variants potentially causal for MGUS. The methodology thus proposed to facilitate our search streamlines risk locus-based interaction, genetic network and pathway enrichment analyses.
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| 5. |
- Chattopadhyay, Subhayan, et al.
(author)
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Genome-wide interaction and pathway-based identification of key regulators in multiple myeloma
- 2019
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2:1
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Journal article (peer-reviewed)abstract
- Inherited genetic susceptibility to multiple myeloma has been investigated in a number of studies. Although 23 individual risk loci have been identified, much of the genetic heritability remains unknown. Here we carried out genome-wide interaction analyses on two European cohorts accounting for 3,999 cases and 7,266 controls and characterized genetic susceptibility to multiple myeloma with subsequent meta-analysis that discovered 16 unique interacting loci. These risk loci along with previously known variants explain 17% of the heritability in liability scale. The genes associated with the interacting loci were found to be enriched in transforming growth factor beta signaling and circadian rhythm regulation pathways suggesting immunoglobulin trait modulation, TH17 cell differentiation and bone morphogenesis as mechanistic links between the predisposition markers and intrinsic multiple myeloma biology. Further tissue/cell-type enrichment analysis associated the discovered genes with hemic-immune system tissue types and immune-related cell types indicating overall involvement in immune response.
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| 6. |
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| 7. |
- Clementson, Martin, et al.
(author)
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Diagnostik och behandling av akuta skafoideumfrakturer
- 2019
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In: Läkartidningen. - 0023-7205. ; 116
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Research review (peer-reviewed)abstract
- This article suggests algorithms for diagnosis and treatment of scaphoid fractures. A clinical suspected scaphoid fracture without signs of fracture on conventional radiographs should have a supplementary MRI done within 5-7 days. Displaced fractures and all proximal fractures should be classified by CT. Fracture union should be evaluated by CT. 90 procent of non- or minimally displaced waist fractures are healed after 6 weeks of conservative treatment. Non- or minimally displaced fractures with signs of instability can be treated conservatively, but require prolonged immobilisation. Fractures with a displacement ≥1,5 mm as well as the majority of proximal scaphoid fractures should be treated surgically with internal fixation.
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| 8. |
- Clementson, Martin, et al.
(author)
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Is early mobilisation better than immobilisation in the treatment of wrist sprains?
- 2016
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In: Journal of Plastic Surgery and Hand Surgery. - 2000-656X. ; :Feb 6, s. 1-5
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Journal article (peer-reviewed)abstract
- Posttraumatic radial sided wrist pain is common and can represent a fracture or a ligament injury. However, in some patients radiographs and MRI are normal, indicating no specific diagnosis other than a wrist sprain. There is no consensus on the ideal treatment for this patient group. The aim was to investigate if patients with posttraumatic radial sided wrist pain and MRI not showing signs of fracture or SL-ligament injury should be treated with immediate mobilisation or 2 weeks cast immobilisation.
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| 9. |
- Clementson, Martin, et al.
(author)
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Long-Term Outcomes After Distal Scaphoid Fractures : A 10-Year Follow-Up
- 2017
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In: The Journal of Hand Surgery. - : Elsevier BV. - 0363-5023. ; 42:11, s. 1-927
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this study was to evaluate the functional, clinical, and radiological outcome 10 years after distal scaphoid fractures. Methods: From a prospective epidemiological study on posttraumatic radial-sided wrist pain, we evaluated 41 cases of distal scaphoid fractures. All cases had been treated nonsurgically in a thumb spica cast. Patients were examined using radiographs, magnetic resonance imaging and computed tomography at the time of injury and with computed tomography after a median of 10 years (range, 8-11 years). Fractures were classified according to a modified Prosser classification system. The primary outcome was assessment of self-reported function using Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Reported Wrist Evaluation (PRWE). Secondary outcomes were clinical status (range of motion and grip and pinch strength) and to evaluate fracture healing and arthritis in the scaphotrapezium-trapezoid (STT) joint. Results: Functional impairment and pain scores at follow-up were low: median DASH score 2, median PRWE 0, and median visual analog scale (VAS) pain score 0. We found no impairment in range of motion or strength. We found 26 type I fractures, 12 type IIA, 1 type IIC, and 2 type IV. There was 1 asymptomatic nonunion in a type I fracture. Computed tomography revealed arthritis in the STT joint in 7 out of 41 wrists, none of which caused clinical symptoms. Conclusions: From an 8- to 11-year perspective, patients with distal scaphoid fractures report normal self-assessed hand function as well as good wrist motion and strength. The risk for development of posttraumatic STT arthritis was low. Type of study/level of evidence: Prognostic II.
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| 10. |
- Clementson, Martin, et al.
(author)
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Union of Scaphoid Waist Fractures Assessed by CT Scan.
- 2015
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In: Journal of Wrist Surgery. - : Georg Thieme Verlag KG. - 2163-3916 .- 2163-3924. ; 4:1, s. 49-55
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Journal article (peer-reviewed)abstract
- Background Union of a scaphoid fracture is difficult to assess on a standard series of radiographs. An unnecessary and prolonged immobilization is inconvenient and may impair functional outcome. Although operative treatment permits early mobilization, its influence on time to union is still uncertain. Purpose To assess union of scaphoid waist fractures based on computed tomography (CT) scan at 6 weeks, and to compare time to union between conservative treatment and arthroscopically assisted screw fixation. Patients and methods CT scan in the longitudinal axis of the scaphoid was used to provide fracture characteristics, and to assess bone union at 6 weeks in 65 consecutive patients with scaphoid waist fractures. In a randomized subgroup from this cohort with nondisplaced fractures, we compared time to union between conservative treatment (n = 23) and arthroscopically assisted screw fixation (n = 15). Results Overall, at 6 weeks we found a 90% union rate for non- or minimally displaced fracture treated conservatively, and 82% for those who underwent surgery. In the randomized subgroup of nondisplaced fractures, no significant difference in time to union was demonstrated between those treated conservatively and those who underwent surgery. The conservatively treated fractures from this subgroup with prolonged time to union (10 to 14 weeks) were comminuted, demonstrating a radial cortical or corticospongious fragment. Conclusion The majority of non- or minimally displaced scaphoid waist fractures are sufficiently treated with 6 weeks in a cast. Screw fixation does not reduce time to fracture union compared with conservative treatment. Level of Evidence level II, Therapeutic study.
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