| 1. |
- Bausch, Birke, et al.
(författare)
-
Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
-
Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
|
|
| 2. |
- Cole, J. W., et al.
(författare)
-
The copy number variation and stroke (CaNVAS) risk and outcome study
- 2021
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose The role of copy number variation (CNV) variation in stroke susceptibility and outcome has yet to be explored. The Copy Number Variation and Stroke (CaNVAS) Risk and Outcome study addresses this knowledge gap. Methods Over 24,500 well-phenotyped IS cases, including IS subtypes, and over 43,500 controls have been identified, all with readily available genotyping on GWAS and exome arrays, with case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome it is planned to: 1) perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension to determine whether the identified stroke-associated CNVs replicate in other ethnically diverse datasets and use biomarker data (e.g. methylation, proteomic, RNA, miRNA, etc.) to evaluate how the identified CNVs exert their effects on stroke risk, and lastly; 3) perform outcome-based Replication and Extension analyses of recent findings demonstrating an inverse relationship between CNV burden and stroke outcome at 3 months (mRS), and then determine the key CNV drivers responsible for these associations using existing biomarker data. Results The results of an initial CNV evaluation of 50 samples from each participating dataset are presented demonstrating that the existing GWAS and exome chip data are excellent for the planned CNV analyses. Further, some samples will require additional considerations for analysis, however such samples can readily be identified, as demonstrated by a sample demonstrating clonal mosaicism. Conclusion The CaNVAS study will cost-effectively leverage the numerous advantages of using existing case-control data sets, exploring the relationships between CNV and IS and its subtypes, and outcome at 3 months, in both men and women, in those of African and European-Caucasian descent, this, across the entire adult-age spectrum. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
|
|
| 3. |
- Pfeiffer, Dorothea, et al.
(författare)
-
Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
-
Ingår i: Stroke. - 1524-4628. ; 50:2, s. 298-304
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
|
|
| 4. |
- Braun, Martin W., et al.
(författare)
-
A 'Model-on-Demand' Identification Methodology for Nonlinear Process Systems
- 2001
-
Ingår i: International Journal of Control. - : Informa UK Limited. - 0020-7179 .- 1366-5820. ; 74:18, s. 1708-1717
-
Tidskriftsartikel (refereegranskat)abstract
- An identification methodology based on multi-level pseudo-random sequence (multi-level PRS) input signals and 'Model-on-Demand' (MoD) estimation is presented for single-input, single-output non-linear process applications. 'Model-on-Demand' estimation allows for accurate prediction of non-linear systems while requiring few user choices and without solving a non-convex optimization problem, as is usually the case with global modelling techniques. By allowing the user to incorporate a priori information into the specification of design variables for multi-level PRS input signals, a sufficiently informative input-output dataset for MoD estimation is generated in a 'plant-friendly' manner. The usefulness of the methodology is demonstrated in case studies involving the identification of a simulated rapid thermal processing (RTP) reactor and a pilot-scale brine-water mixing tank. On the resulting datasets, MoD estimation displays performance comparable to that achieved via semi-physical modelling and semi-physical modelling combined with neural networks. The MoD estimator, however, achieves this level of performance with substantially lower engineering effort.
|
|
| 5. |
- Christofer Juhlin, C., et al.
(författare)
-
Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene
- 2015
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley: 12 months. - 1045-2257 .- 1098-2264. ; 54:9, s. 542-554
-
Tidskriftsartikel (refereegranskat)abstract
- As subsets of pheochromocytomas (PCCs) lack a defined molecular etiology, we sought to characterize the mutational landscape of PCCs to identify novel gene candidates involved in disease development. A discovery cohort of 15 PCCs wild type for mutations in PCC susceptibility genes underwent whole-exome sequencing, and an additional 83 PCCs served as a verification cohort for targeted sequencing of candidate mutations. A low rate of nonsilent single nucleotide variants (SNVs) was detected (6.1/sample). Somatic HRAS and EPAS1 mutations were observed in one case each, whereas the remaining 13 cases did not exhibit variants in established PCC genes. SNVs aggregated in apoptosis-related pathways, and mutations in COSMIC genes not previously reported in PCCs included ZAN, MITF, WDTC1, and CAMTA1. Two somatic mutations and one constitutional variant in the well-established cancer gene lysine (K)-specific methyltransferase 2D (KMT2D, MLL2) were discovered in one sample each, prompting KMT2D screening using focused exome-sequencing in the verification cohort. An additional 11 PCCs displayed KMT2D variants, of which two were recurrent. In total, missense KMT2D variants were found in 14 (11 somatic, two constitutional, one undetermined) of 99 PCCs (14%). Five cases displayed somatic mutations in the functional FYR/SET domains of KMT2D, constituting 36% of all KMT2D-mutated PCCs. KMT2D expression was upregulated in PCCs compared to normal adrenals, and KMT2D overexpression positively affected cell migration in a PCC cell line. We conclude that KMT2D represents a recurrently mutated gene with potential implication for PCC development. (c) 2015 The Authors. Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc.
|
|
| 6. |
- Dalin, Martin, 1982, et al.
(författare)
-
Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.
|
|
| 7. |
- Dufwenberg, Martin, 1964, et al.
(författare)
-
Mean markets or kind commerce?
- 2022
-
Ingår i: Journal of Public Economics. - : Elsevier BV. - 0047-2727. ; 209
-
Tidskriftsartikel (refereegranskat)abstract
- Does market interaction influence morality? We study a particular angle of this classic question theoret-ically and experimentally. The novelty of our approach is to posit that people are motivated by reciprocity - an urge many argue affects humans. While many have suggested that market interactions make people more selfish, our reciprocity-based theory allows that market interaction on the contrary induces more prosociality. Our experiment provides a test of the empirical relevance of such an effect, in some highly stylized settings. The results are broadly (but not completely) supportive. They may shed light on the development of morality and prosocial behavior over time, with respect to episodes in history where the nature of commerce was transformed.(c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 8. |
- Grönberg, Angelina, et al.
(författare)
-
Incidence of Aphasia in Ischemic Stroke
- 2022
-
Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 56:3, s. 174-182
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: A decrease in ischemic stroke (IS) incidence has been observed in high income countries during the last decades. Whether this has influenced the occurrence of aphasia in IS is uncertain. We therefore examined the incidence rate and potentially related determinants of aphasia in IS. Methods: We prospectively examined consecutive patients admitted to hospital with first-ever acute IS between March 1, 2017, and February 28, 2018, as part of the Lund Stroke Register (LSR) Study, comprising patients from the uptake area of Skåne University Hospital, Lund, Sweden. Patients were assessed with National Institutes of Health Stroke Scale (NIHSS) at stroke onset. Presence of aphasia was evaluated with NIHSS item 9 (language). We registered IS subtypes and risk factors. To investigate possible temporal changes in aphasia incidence, we made comparisons with corresponding LSR data from 2005 to 2006. Incidence rates were calculated and adjusted to the European Standard Population (ESP) and to the Swedish population. Results: Among 308 included IS patients, 30% presented with aphasia (n = 91; 95% CI: 25-35), a proportion of aphasia in IS that was similar to 2005-2006. The incidence rate of aphasia was 31 per 100,000 person-years adjusted to the ESP (95% CI: 25-38 per 100,000 person-years) corresponding to a significant decrease of 30% between 2005-2006 and 2017-2018. The decrease was significantly more pronounced in men. The initial severity of aphasia remained unchanged, with the majority of patients having severe to global aphasia. No significant differences between vascular stroke risk factors were noted among stroke patients with or without aphasia. Conclusion: Even though the overall IS incidence rate has decreased during the first decades of the 21st century, the proportion of IS patients with aphasia at stroke onset remains stable at 30%. Aphasia continues to be an important symptom that needs to be considered in stroke care and rehabilitation.
|
|
| 9. |
- Nilsson, Magnus, et al.
(författare)
-
A 9-band WCDMA/EDGE transceiver supporting HSPA evolution
- 2011
-
Ingår i: [Host publication title missing]. - 0193-6530. ; , s. 366-368
-
Konferensbidrag (refereegranskat)abstract
- The future of cellular radio ICs lies in the integration of an ever-increasing number of bands and channel bandwidths. This paper presents a transceiver together with the associated discrete front-end components. The transceiver supports 4 EDGE bands and 9 WCDMA bands (l-VI and Vlll-X), while the radio can be configured to simultaneously support the 4 EDGE bands and up to 5 WCDMA bands: 3 high bands (HB) and 2 low bands (LB). The RX is a SAW-less homodyne composed of a main RX and a diversity RX. To reduce package complexity with so many bands, we chose to minimize the number of ports by using single-ended RF interfaces for both RX and TX. This saves seve ral package pins, but requires careful attention to grounding. The main RX has 8 LNA ports and the diversity RX has 5, with some LNAs supporting multiple bands. On the TX side, 2 ports are used for all EDGE bands and 4 for the WCDMA bands.
|
|
| 10. |
- Palm, Martin, et al.
(författare)
-
The Effect of Heavy Metals on Conjugation Efficiency of an F-Plasmid in Escherichia coli.
- 2022
-
Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Conjugation, the process by which conjugative plasmids are transferred between bacteria, is regarded as a major contributor to the spread of antibiotic resistance, in both environmental and clinical settings. Heavy metals are known to co-select for antibiotic resistance, but the impact of the presence of these metals on conjugation itself is not clear. Here, we systematically investigate the impact that five heavy metals (arsenic, cadmium, copper, manganese, and zinc) have on the transfer of an IncF conjugative plasmid in Escherichia coli. Our results show that two of the metals, cadmium and manganese, have no significant impact, while arsenic and zinc both reduce conjugation efficiency by approximately 2-fold. Copper showed the largest impact, with an almost 100-fold decrease in conjugation efficiency. This was not mediated by any change in transcription from the major Py promoter responsible for transcription of the conjugation machinery genes. Further, we show that in order to have this severe impact on the transfer of the plasmid, copper sulfate needs to be present during the mating process, and we suggest explanations for this.
|
|
| 11. |
- Pfeiffer, D., et al.
(författare)
-
Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
-
Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:2, s. 298-304
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods-Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/ GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of = 3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results-The study sample comprised 816 CADISP patients (age 44.2 +/- 10.3 years) and 2498 SiGN/GISCOME patients (age 67.7 +/- 14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions-Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
|
|
| 12. |
- Qiao, Jia Lu, et al.
(författare)
-
A novel scatterplot-based method to detect copy number variation (CNV)
- 2023
-
Ingår i: Frontiers in Genetics. - 1664-8021. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Most methods to detect copy number variation (CNV) have high false positive rates, especially for small CNVs and in real-life samples from clinical studies. In this study, we explored a novel scatterplot-based method to detect CNVs in microarray samples. Methods: Illumina SNP microarray data from 13,254 individuals were analyzed with scatterplots and by PennCNV. The data were analyzed without the prior exclusion of low-quality samples. For CNV scatterplot visualization, the median signal intensity of all SNPs located within a CNV region was plotted against the median signal intensity of the flanking genomic region. Since CNV causes loss or gain of signal intensities, carriers of different CNV alleles pop up in clusters. Moreover, SNPs within a deletion are not heterozygous, whereas heterozygous SNPs within a duplication show typical 1:2 signal distribution between the alleles. Scatterplot-based CNV calls were compared with standard results of PennCNV analysis. All discordant calls as well as a random selection of 100 concordant calls were individually analyzed by visual inspection after noise-reduction. Results: An algorithm for the automated scatterplot visualization of CNVs was developed and used to analyze six known CNV regions. Use of scatterplots and PennCNV yielded 1019 concordant and 108 discordant CNV calls. All concordant calls were evaluated as true CNV-findings. Among the 108 discordant calls, 7 were false positive findings by the scatterplot method, 80 were PennCNV false positives, and 21 were true CNVs detected by the scatterplot method, but missed by PennCNV (i.e., false negative findings). Conclusion: CNV visualization by scatterplots allows for a reliable and rapid detection of CNVs in large studies. This novel method may thus be used both to confirm the results of genome-wide CNV detection software and to identify known CNVs in hitherto untyped samples.
|
|
| 13. |
- Stenman, Anders, et al.
(författare)
-
Comparison of Global Nonlinear Models and "Model-on-Demand" Estimation Applied to Identification of a RTP Wafer Reactor
- 1999
-
Ingår i: Preceedings of the 38th IEEE Conference on Decision and Control. - Linköping : Linköping University Electronic Press. - 0780352505 ; , s. 3950-3955 vol.4
-
Konferensbidrag (refereegranskat)abstract
- "Model on Demand" (MoD) simulation of the temperature dynamics in a simulated Rapid Thermal Process-ing (RTP) reactor is compared against various types of global models (ARX, semiphysical, combined semiphysical with neural net). The identication data is generated from a m-level pseudo-random sequence input whose parameters are specied systematically using a priori information readily available to the engineer. The MoD estimator outperforms the ARX model and two semi-physical models, while matching the performance of a combined semi-physical with neural net model. This makes MoD estimation an appealing alternative to global methods because of its reduced engineering eort and simplified a priori knowledge regarding model structure.
|
|
| 14. |
- Stenman, Adam, et al.
(författare)
-
HRAS mutation prevalence and associated expression patterns in pheochromocytoma
- 2016
-
Ingår i: Genes, Chromosomes and Cancer. - : WILEY-BLACKWELL. - 1045-2257 .- 1098-2264. ; 55:5, s. 452-459
-
Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo-hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been verified in sporadic PPGLs. In order to further establish the HRAS mutation frequency and to characterize the associated expression profiles of HRAS mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the HRAS gene was screened, and compared with microarray-based gene expression profiles for 93 of the cases. The activating HRAS mutations G13R, Q61R, and Q61K were found in 10/142 PCC (7.0%) and a Q61L mutation was revealed in 1/14 PGL (7.1%). All HRAS mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 HRAS wild-type PPGL. Somatic HRAS mutations were not revealed in cases with known PPGL susceptibility gene mutations and all HRAS mutated cases were benign. The HRAS mutation prevalence of all PPGL published up to date is 5.2% (49/950), and 8.8% (48/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of HRAS mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. HRAS mutated PPGL cluster together with NF1- and RET-mutated tumors associated with activation of kinase-signaling pathways.
|
|
| 15. |
- Stenman, Caroline, et al.
(författare)
-
Degree of differentiation of cutaneous squamous cell carcinoma: a comparison between a Swedish cohort of organ transplant recipients and immunocompetent patients.
- 2018
-
Ingår i: Dermatology practical & conceptual. - : Mattioli1885. - 2160-9381. ; 8:4, s. 330-336
-
Tidskriftsartikel (refereegranskat)abstract
- Organ transplant recipients (OTRs) have a very high risk of developing cutaneous squamous cell carcinoma (cSCC). Immunosuppressed OTRs may have a higher proportion of poorly differentiated cSCC than non-OTRs.The aim of this study was to investigate the degree of differentiation of cSCCs in OTRs compared with immunocompetent individuals.Data from the Swedish Cancer Registry were crosschecked with data from the Transplant registry of the Transplant Institute at Sahlgrenska University Hospital in Gothenburg, Sweden. All OTRs with a diagnosis of cSCC, basosquamous carcinoma, and/or cSCC in situ established at the Department of Dermatology, Sahlgrenska University Hospital, during 2002-2015 were included. The control group consisted of non-OTRs with the same diagnoses during the same time period.During 2002-2015, 82 OTRs diagnosed with 515 tumors and 883 non-OTRs with 1,247 tumors were included. OTRs developed 0.47 tumors/year vs 0.10 tumors/year for non-OTRs, but no significant differences were observed in the degree of tumor differentiation of invasive cSCCs between OTRs and non-OTRs (P = 0.4). The distribution of poorly, moderately, and well-differentiated invasive cSCCs among OTRs and non-OTRs were 8.5% vs 12.5%, 22.1% vs 29.9%, and 69.4% vs 57.6%, respectively.OTRs do not develop a higher proportion of poorly differentiated cSCCs than non-OTRs.
|
|
| 16. |
- Stenman, Caroline, et al.
(författare)
-
Sun protection behaviour in organ transplant recipients and non-transplant patients attending a dermatology outpatient clinic in Sweden: A questionnaire survey
- 2022
-
Ingår i: Photodermatology Photoimmunology & Photomedicine. - : Wiley. - 0905-4383 .- 1600-0781. ; 38:2, s. 132-140
-
Tidskriftsartikel (refereegranskat)abstract
- Background/purpose Organ transplant recipients (OTRs) are at high risk of developing skin cancer and are therefore advised to protect their skin against ultraviolet radiation from the sun. Specialized OTR clinics with dermatological follow-up may improve sun habits among OTRs. In this study, we compared self-reported sun exposure and sun protection behaviour between OTRs and non-transplant patients (non-TPs) and between OTRs with and without special dermatological follow-up. Methods Patients from Sahlgrenska University Hospital, Gothenburg, Sweden, completed a sun exposure questionnaire. Between 2011 and 2015, 282 OTRs transplanted in the period 1976-2014 and 414 non-TPs were recruited among dermatological outpatients. Participants were stratified into five groups by their status as OTRs or non-TPs and by attendance to dermatological follow-up. Results More non-TPs than OTRs reported one or more sunburns in the past year, 46% vs. 20%, P < .0001). More OTRs with than OTRs without dermatological follow-up reported frequent use of sunscreens (63% vs 44%, P = .006). More OTRs with follow-up used one or more sun protection measure such as covering clothes, than other OTRs (54% vs 34%, P = .016). Conclusion In this study, OTRs reported less sun exposure than non-TPs. Specialized dermatological follow-up seems to improve sun protection behaviour among OTRs. We suggest that specialized OTR clinics should be more broadly implemented.
|
|
| 17. |
|
|
| 18. |
- Vigil-Stenman, Theoden, et al.
(författare)
-
High abundance and expression of transposases in bacteria from the Baltic Sea
- 2017
-
Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 11:11, s. 2611-2623
-
Tidskriftsartikel (refereegranskat)abstract
- Transposases are mobile genetic elements suggested to have an important role in bacterial genome plasticity and host adaptation but their transcriptional activity in natural bacterial communities is largely unexplored. Here we analyzed metagenomes and -transcriptomes of size fractionated (0.1-0.8, 0.8-3.0 and 3.0-200 mu m) bacterial communities from the brackish Baltic Sea, and adjacent marine waters. The Baltic Sea transposase levels, up to 1.7% of bacterial genes and 2% of bacterial transcripts, were considerably higher than in marine waters and similar to levels reported for extreme environments. Large variations in expression were found between transposase families and groups of bacteria, with a two-fold higher transcription in Cyanobacteria than in any other phylum. The community-level results were corroborated at the genus level by Synechococcus transposases reaching up to 5.2% of genes and 6.9% of transcripts, which is in contrast to marine Synechococcus that largely lack these genes. Levels peaked in Synechococcus from the largest size fraction, suggesting high frequencies of lateral gene transfer and high genome plasticity in colony-forming picocyanobacteria. Together, the results support an elevated rate of transposition-based genome change and adaptation in bacterial populations of the Baltic Sea, and possibly also of other highly dynamic estuarine waters.
|
|
| 19. |
- Vigil-Stenman, Theoden, et al.
(författare)
-
High transcriptional activity of insertion sequences in Baltic Sea microorganisms
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Insertion sequences (ISs) are mobile genetic elements found in almost all prokaryotic genomes. They consist of a gene encoding a transposase, surrounded by inverted repeats. The transposase has the ability to excise the IS and insert it elsewhere in the genome, a process referred to as transposition. ISs have high copy numbers in prokaryotes inhabiting “extreme” environments, and it is proposed that their activity facilitates adaptation to environmental changes and subsequent adaptive evolution. The initial step in the transposition of an IS is the transcription of the open reading frame encoding the transposase. In an effort to evaluate the presence, activity and role of ISs in microbes of a temperate water body offering steep changes in salinity and nutrient conditions, the metatranscriptomes and metagenomes of ten water samples from the brackish water Baltic Sea were examined. ISs in the limnic Lake Torne Träsk, the marine waters off the Swedish west coast and off the coast of California were included to get perspective. The results reveal that insertion sequences make up a considerably higher fraction of the metatranscriptomes of brackish waters (0.3-1.8%) than of marine waters (0.0005-0.2%), and that the IS fraction of the metatranscriptome is commonly double that of the IS fraction of the metagenome. From these data it is concluded that ISs occupy a significant part of Baltic Sea bacterial transcription activity, in line with their proposed function as facilitators of adaptive change to changing and stressful environments.
|
|
