1. |
- Allesøe, Rosa Lundbye, et al.
(author)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Journal article (peer-reviewed)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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2. |
- Adel Fahmideh, Maral, et al.
(author)
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A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk.
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- Genetic risk score (GRS) is used to demonstrate the genetic variants contributing to the polygenic architecture of complex diseases. By using a GRS, we have investigated the additive impact of the known adult glioma susceptibility loci on the pediatric brain tumor (PBT) risk and assessed the proportion of PBT heritability attributable to these susceptibility loci. A GRS was generated for PBTs based on the alleles and associated effect sizes derived from a previously published genome-wide association study on adult glioma. The GRS was calculated in CEFALO, a population-based case-control study of brain tumors in children and adolescents including saliva DNA of 245 cases and 489 controls. The unconditional logistic regression model was used to investigate the association between standardized GRS and risk of PBTs. To measure the variance explained by the effect of GRS, Nagelkerke pseudo-R2 was calculated. The GRS for adult brain tumors was associated with an increased risk of PBTs (OR 1.25 [95% CI 1.06-1.49], p=0.009) and 0.3% of the variance in PBTs could be explained by the effect of GRS on the liability scale. This study provides evidence that heritable risks of PBTs are in-part attributable to some common genetic variants associated with adult glioma.
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3. |
- Adel Fahmideh, Maral, et al.
(author)
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Common genetic variations in cell cycle and DNA repair pathways associated with pediatric brain tumor susceptibility
- 2016
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In: Oncotarget. - Stockholm : Karolinska Institutet, Institute of Environmental Medicine. - 1949-2553.
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Journal article (peer-reviewed)abstract
- Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. The results showed EGFRrs730437 and EGFRrs11506105 may decrease susceptibility to PBTs, whereas ERCC1rs3212986 may increase risk of these tumors. Moreover, stratifid analyses indicated CHAF1Ars243341, CHAF1Ars2992, and XRCC1rs25487 were associated with a decreased risk of astrocytoma subtype. Furthermore, an increased risk of non-astrocytoma subtype associated with EGFRrs9642393, EME1rs12450550, ATMrs170548, and GLTSCRrs1035938 as well as a decreased risk of this subtype associated with XRCC4rs7721416 and XRCC4rs2662242 were detected. This study indicates SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, cell cycle and DNA repair pathways variations associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting pediatric and adult brain tumors might share similar etiological pathways.
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4. |
- Aydin, Denis, et al.
(author)
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Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.
- 2011
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 103:16, s. 1264-76
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Journal article (peer-reviewed)abstract
- It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents.
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5. |
- Brisbois, J., et al.
(author)
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Flux penetration in a superconducting film partially capped with a conducting layer
- 2017
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 95:9
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Journal article (peer-reviewed)abstract
- The influence of a conducting layer on the magnetic flux penetration in a superconducting Nb film is studied by magneto-optical imaging. The metallic layer partially covering the superconductor provides an additional velocity-dependent damping mechanism for the flux motion that helps to protect the superconducting state when thermomagnetic instabilities develop. If the flux advances with a velocity slower than omega = 2/mu(0)sigma t, where sigma is the cap layer conductivity and t is its thickness, the flux penetration remains unaffected, whereas for incoming flux moving faster than w, the metallic layer becomes an active screening shield. When the metallic layer is replaced by a perfect conductor, it is expected that the flux braking effect will occur for all flux velocities. We investigate this effect by studying Nb samples with a thickness step. Some of the observed features, namely the deflection of the flux trajectories at the border of the thick center, as well as the favored flux penetration at the indentation, are reproduced by time-dependent Ginzburg-Landau simulations.
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6. |
- Dahlin, Anna M., 1979-, et al.
(author)
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A genome-wide association study on medulloblastoma
- 2020
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In: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
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Journal article (peer-reviewed)abstract
- Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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7. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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8. |
- Lonn, Stefan, et al.
(author)
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Mobile phone use and risk of parotid gland tumor
- 2006
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:7, s. 637-643
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Journal article (peer-reviewed)abstract
- Handheld mobile phones were introduced in Denmark and Sweden during the late 1980s. This makes the Danish and Swedish populations suitable for a study aimed at testing the hypothesis that long-term mobile phone use increases the risk of parotid gland tumors. In this population-based case-control study, the authors identified all cases aged 20-69 years diagnosed with parotid gland tumor during 2000-2002 in Denmark and certain parts of Sweden. Controls were randomly selected from the study population base. Detailed information about mobile phone use was collected from 60 cases of malignant parotid gland tumors (85% response rate), 112 benign pleomorphic adenomas (88% response rate), and 681 controls (70% response rate). For regular mobile phone use, regardless of duration, the risk estimates for malignant and benign tumors were 0.7 (95% confidence interval: 0.4, 1.3) and 0.9 (95% confidence interval: 0.5, 1.5), respectively. Similar results were found for more than 10 years' duration of mobile phone use. The risk estimate did not increase, regardless of type of phone and amount of use. The authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of parotid gland tumors.
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9. |
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10. |
- McCarthy, Bridget J, et al.
(author)
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Risk factors for oligodendroglial tumors : A pooled international study
- 2011
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In: Neuro-Oncology. - Charlottesville, VA : Carden Jennings Pub.. - 1522-8517 .- 1523-5866. ; 13:2, s. 242-250
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Journal article (peer-reviewed)abstract
- Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
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11. |
- Motta, M., et al.
(author)
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Controllable morphology of flux avalanches in microstructured superconductors
- 2014
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In: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 89:13
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Journal article (peer-reviewed)abstract
- The morphology of abrupt bursts of magnetic flux into superconducting films with engineered periodic pinning centers (antidots) has been investigated. Guided flux avalanches of thermomagnetic origin develop a treelike structure, with the main trunk perpendicular to the borders of the sample, while secondary branches follow well-defined directions determined by the geometrical details of the underlying periodic pinning landscape. Strikingly, we demonstrate that in a superconductor with relatively weak random pinning the morphology of such flux avalanches can be fully controlled by proper combinations of lattice symmetry and antidot geometry. Moreover, the resulting flux patterns can be reproduced, to the finest details, by simulations based on a phenomenological thermomagnetic model. In turn, this model can be used to predict such complex structures and to estimate physical variables of more difficult experimental access, such as the local values of temperature and electric field.
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12. |
- Motta, M., et al.
(author)
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Enhanced pinning in superconducting thin films with graded pinning landscapes
- 2013
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 102:21
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Journal article (peer-reviewed)abstract
- A graded distribution of antidots in superconducting a-Mo79Ge21 thin films has been investigated by magnetization and magneto-optical imaging measurements. The pinning landscape has maximum density at the sample border, decreasing linearly towards the center. Its overall performance is noticeably superior than that for a sample with uniformly distributed antidots: For high temperatures and low fields, the critical current is enhanced, whereas the region of thermomagnetic instabilities in the field-temperature diagram is significantly suppressed. These findings confirm the relevance of graded landscapes on the enhancement of pinning efficiency, as recently predicted by Misko and Nori.
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13. |
- Olsson, Ann, et al.
(author)
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Survival of glioma patients in relation to mobile phone use in Denmark, Finland and Sweden
- 2019
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In: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 141:1, s. 139-149
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Journal article (peer-reviewed)abstract
- Purpose: Gliomas are the most common cancer of the brain, with a poor prognosis in particular for glioblastoma. In 2014, a study suggested reduced survival in relation to latency of mobile phone use among glioblastoma patients. A joint epidemiological/experimental project to study effects of RF-EMF on tumor development and progression was established. The current analysis relates to the epidemiological part and addresses whether pre-diagnostic mobile phone use was associated with survival among glioma patients.Methods: Glioma cases (n = 806) previously enrolled in a collaborative population-based case–control study in Denmark, Finland and Sweden were followed up for survival. Vital status, date of death, date of emigration, or date last known to be alive was obtained based on registry linkages with a unique personal ID in each country. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) stratified by country. Covariates investigated were sex, age, education, histology, treatment, anatomic location and marital status.Results: No indication of reduced survival among glioblastoma patients was observed for various measures of mobile phone use (ever regular use, time since start of regular use, cumulative call time overall or in the last 12 months) relative to no or non-regular use. All significant associations suggested better survival for mobile phone users. Results were similar for high-grade and low-grade gliomas.Conclusions: We found no evidence of reduced survival among glioma patients in relation to previous mobile phone use.
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14. |
- Tettamanti, Giorgio, et al.
(author)
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Long-term effect of mobile phone use on sleep quality : Results from the cohort study of mobile phone use and health (COSMOS)
- 2020
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 140
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Journal article (peer-reviewed)abstract
- Background: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes.Materials and methods: The study included Swedish (n = 21,049) and Finnish (n = 3120) participants enrolled in the Cohort Study of Mobile Phone Use and Health (COSMOS) with information about operator-recorded mobile phone use at baseline and sleep outcomes both at baseline and at the 4-year follow-up. Sleep disturbance, sleep adequacy, daytime somnolence, sleep latency, and insomnia were assessed using the Medical Outcome Study (MOS) sleep questionnaire.Results: Operator-recorded mobile phone use at baseline was not associated with most of the sleep outcomes. For insomnia, an odds ratio (OR) of 1.24, 95% CI 1.03-1.51 was observed in the highest decile of mobile phone call-time (> 258 min/week). With weights assigned to call-time to account for the lower RF-EMF exposure from Universal Mobile Telecommunications Service (UMTS, 3G) than from Global System for Mobile Communications (GSM, 2G) the OR was 1.09 (95% CI 0.89-1.33) in the highest call-time decile.Conclusion: Insomnia was slightly more common among mobile phone users in the highest call-time category, but adjustment for the considerably lower RF-EMF exposure from the UMTS than the GSM network suggests that this association is likely due to other factors associated with mobile phone use than RF-EMF. No association was observed for other sleep outcomes. In conclusion, findings from this study do not support the hypothesis that RF-EMF from mobile phone use has long-term effects on sleep quality.
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15. |
- Tettamanti, Giorgio, et al.
(author)
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Prenatal and postnatal medical conditions and the risk of brain tumors in children and adolescents: an international multicenter case-control study.
- 2017
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In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 26:1
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Journal article (peer-reviewed)abstract
- Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans.Information regarding medical conditions, including prenatal and postnatal exposure to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden and Switzerland through face to face interview. Eligible cases of childhood and adolescent brain tumors (CABTs) were aged 7 to 19 years, diagnosed between January 1, 2004 and August 31, 2008 and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls.Prenatal exposure to medical diagnostic radiation and postnatal exposure to x-rays were not associated with CABTs. A higher risk estimate of CABTs, although not statistically significant, was found for exposure to head CT scan (OR = 1.86, 95% CI 0.82-4.22). The associations with head injury, febrile seizure, fever in the first 12 weeks, and general anesthesia were close to unity.Prenatal or postnatal medical conditions, including medical diagnostic radiation, were not associated with CABTs. Based on small numbers of exposed children, we observed a non-significant increased risk for CT scans of the head.We have presented additional evidence suggesting that exposure to head CT scan may be associated with the occurrence of CABTs.
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16. |
- Toledano, Mireille B., et al.
(author)
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An international prospective cohort study of mobile phone users and health (COSMOS) : Factors affecting validity of self-reported mobile phone use
- 2018
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In: International journal of hygiene and environmental health. - : Elsevier GmbH - Urban und Fischer. - 1438-4639 .- 1618-131X. ; 221:1, s. 1-8
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Journal article (peer-reviewed)abstract
- This study investigates validity of self-reported mobile phone use in a subset of 75 993 adults from the COSMOS cohort study. Agreement between self-reported and operator-derived mobile call frequency and duration for a 3-month period was assessed using Cohen's weighted Kappa (κ). Sensitivity and specificity of both self-reported high (≥10 calls/day or ≥4h/week) and low (≤6 calls/week or <30min/week) mobile phone use were calculated, as compared to operator data. For users of one mobile phone, agreement was fair for call frequency (κ=0.35, 95% CI: 0.35, 0.36) and moderate for call duration (κ=0.50, 95% CI: 0.49, 0.50). Self-reported low call frequency and duration demonstrated high sensitivity (87% and 76% respectively), but for high call frequency and duration sensitivity was lower (38% and 56% respectively), reflecting a tendency for greater underestimation than overestimation. Validity of self-reported mobile phone use was lower in women, younger age groups and those reporting symptoms during/shortly after using a mobile phone. This study highlights the ongoing value of using self-report data to measure mobile phone use. Furthermore, compared to continuous scale estimates used by previous studies, categorical response options used in COSMOS appear to improve validity considerably, most likely by preventing unrealistically high estimates from being reported.
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