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| 2. |
- Deans, Andrew R, et al.
(författare)
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Finding Our Way through Phenotypes.
- 2015
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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| 5. |
- Forner, L. E., et al.
(författare)
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Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1
- 2022
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 166, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. Methods and materials: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. Results: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. Conclusion: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error. © 2021 The Authors
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| 7. |
- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 8. |
- Baron, J. S., et al.
(författare)
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Synthesis Centers as Critical Research Infrastructure
- 2017
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Ingår i: Bioscience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:8, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis centers offer a unique amalgam of culture, infrastructure, leadership, and support that facilitates creative discovery on issues crucial to science and society. The combination of logistical support, postdoctoral or senior fellowships, complex data management, informatics and computing capability or expertise, and most of all, opportunity for group discussion and reflection lowers the "activation energy" necessary to promote creativity and the cross-fertilization of ideas. Synthesis centers are explicitly created and operated as community-oriented infrastructure, with scholarly directions driven by the ever-changing interests and needs of an open and inclusive scientific community. The last decade has seen a rise in the number of synthesis centers globally but also the end of core federal funding for several, challenging the sustainability of the infrastructure for this key research strategy. Here, we present the history and rationale for supporting synthesis centers, integrate insights arising from two decades of experience, and explore the challenges and opportunities for long-term sustainability.
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| 11. |
- Aarup, Lasse Rye, et al.
(författare)
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The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: Implications for tumour coverage
- 2009
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 91:3, s. 405-414
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate against Monte-Carlo the performance of various dose calculations algorithms regarding lung turnout coverage in stereotactic body radiotherapy (SBRT) conditions. Materials and methods: Dose distributions in virtual lung phantoms have been calculated using four commercial Treatment Planning System (TPS) algorithms and one Monte Carlo (MC) system (EGSnrc). We compared the performance of the algorithms in calculating the target dose for different degrees of lung inflation. The phantoms had a cubic 'body' and 'lung' and a central 2-cm diameter spherical 'tumour' (the body and turnout have unit density). The lung tissue was assigned five densities (rho(lung)): 0.01, 0.1, 0.2, 0.4 and 1 g/cm(3). Four-field treatment plans were calculated with 6- and 18 MV narrow beams for each value of rho(lung). We considered the Pencil Beam Convolution (PBCEl) and the Analytical Anisotropic Algorithm (AAA(ECl)) from Varian Eclipse and the Pencil Beam Convolution (PBCOMP) and the Collapsed Cone Convolution (CCCOMP) algorithms from Oncentra MasterPlan. Results: When changing rho(lung) from 0.4 to 0.1 g/cm(3), the MC median target dose decreased from 89.2% to 74.9% for 6 MV and from 83.3% to 61.6% for 18 MV (of dose maximum in the homogenous case at both energies), while for both PB algorithms the median target dose was virtually independent of lung density. Conclusions: Both PB algorithms overestimated the target dose, the overestimation increasing as rho(lung) decreased. Concerning target dose, the AAA(ECl) and CCCOMP algorithms appear to be adequate alternatives to MC. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and oncology 91 (2009) 405-414
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| 12. |
- Bräuner, Elvira Vaclavik, et al.
(författare)
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Health Effects of PCBs in Residences and Schools (HESPERUS) : PCB - Health Cohort Profile
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated-biphenyls (PCBs) were introduced in the late 1920s and used until the 1970s when they were banned in most countries due to evidence of environmental build-up and possible adverse health effects. However they still persist in the environment, indoors and in humans. Indoor air in contaminated buildings may confer airborne exposure markedly above background regional PCB levels. To date, no epidemiological studies have assessed the health effects from exposure to semi-volatile PCBs in the indoor environment. Indoor air PCBs are generally less chlorinated than PCBs that are absorbed via the diet, or via past occupational exposure; therefore their health effects require separate risk assessment. Two separate cohorts of individuals who have either attended schools (n = 66,769; 26% exposed) or lived in apartment buildings (n = 37,185; 19% exposed), where indoor air PCB concentrations have been measured were created. An individual estimate of long-term airborne PCB exposure was assigned based on measurements. The cohorts will be linked to eight different national data sources on mortality, school records, residential history, socioeconomic status, and chronic disease and reproductive outcomes. The linking of indoor air exposures with health outcomes provides a dataset unprecedented worldwide. We describe a project, called HESPERUS (Health Effects of PCBs in Residences and Schools), which will be the first study of the long term health effects of the lower-chlorinated, semi-volatile PCBs in the indoor environment.
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| 15. |
- Høyer, Birgit Bjerre, et al.
(författare)
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Impact of Di-2-Ethylhexyl Phthalate Metabolites on Male Reproductive Function : a Systematic Review of Human Evidence
- 2018
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Ingår i: Current Environmental Health Reports. - : Springer Science and Business Media LLC. - 2196-5412. ; 5:1, s. 20-33
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of this review is to systematically review the literature linking di-2-ethylhexyl phthalate (DEHP) exposure with effects on reproductive health in adult males. RECENT FINDINGS: Thirty-three papers were included of which 28 were cross-sectional. Twenty-one papers investigated semen samples, 18 investigated reproductive hormones, and three studies investigated time to pregnancy. Studies revealed some but inconsistent indications that higher urinary DEHP metabolite levels are associated with an increase in the proportion of spermatozoa with damaged DNA and to a decrease in sperm concentration and motility. A negative association between DEHP metabolites and testosterone levels was more consistent. DEHP metabolites do not seem to be associated with a delay in time to pregnancy, but data are sparse. The studies on DEHP exposure and reproductive biomarkers in men converge to support the hypothesis that DEHP exposure is related to impaired male reproductive function. Longitudinal studies are needed to establish if the observed associations are causal.
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| 16. |
- Leter, Giorgio, et al.
(författare)
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Exposure to Perfluoroalkyl Substances and Sperm DNA Global Methylation in Arctic and European Populations
- 2014
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Ingår i: Environmental and Molecular Mutagenesis. - : Wiley. - 1098-2280 .- 0893-6692. ; 55:7, s. 591-600
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFASs) are widely used in a variety of industrial processes and products, and have been detected globally in humans and wildlife. PFASs are suspected to interfere with endocrine signaling and to adversely affect human reproductive health. The aim of the present study was to investigate the associations between exposure to PFASs and sperm global methylation levels in a population of non-occupationally exposed fertile men. Measurements of PFASs in serum from 262 partners of pregnant women from Greenland, Poland and Ukraine, were also carried out by liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) were detected in 97% of the blood samples. Two surrogate markers were used to assess DNA global methylation levels in semen samples from the same men: (a) average DNA methylation level in repetitive DNA sequences (Alu, LINE-1, Sat alpha) quantified by PCR-pyrosequencing after bisulfite conversion; (b) flow cytometric immunodetection of 5-methyl-cytosines. After multivariate linear regression analysis, no major consistent associations between PFASs exposure and sperm DNA global methylation endpoints could be detected. However, since weak but statistically significant associations of different PFASs with DNA hypo- and hypermethylation were found in some of the studied populations, effects of PFASs on sperm epigenetic processes cannot be completely excluded, and this issue warrants further investigation. (C) 2014 Wiley Periodicals, Inc.
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| 18. |
- Moczek, Armin P., et al.
(författare)
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The significance and scope of evolutionary developmental biology : a vision for the 21st century
- 2015
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Ingår i: Evolution & development. ; 17:3, s. 198-219
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary developmental biology (evo-devo) has undergone dramatic transformations since its emergence as a distinct discipline. This paper aims to highlight the scope, power, and future promise of evo-devo to transform and unify diverse aspects of biology. We articulate key questions at the core of eleven biological disciplines-from Evolution, Development, Paleontology, and Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary Developmental Biology itself-and discuss why evo-devo is uniquely situated to substantially improve our ability to find meaningful answers to these fundamental questions. We posit that the tools, concepts, and ways of thinking developed by evo-devo have profound potential to advance, integrate, and unify biological sciences as well as inform policy decisions and illuminate science education. We look to the next generation of evolutionary developmental biologists to help shape this process as we confront the scientific challenges of the 21st century.
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| 21. |
- Sirivåg, K, et al.
(författare)
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Physical EXercise Augmented COGnitive Behaviour Therapy for Older Adults with Generalised Anxiety Disorder (PEXACOG)
- 2016
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Konferensbidrag (refereegranskat)abstract
- Generalised anxiety disorder (GAD) is the most prevalent severe anxiety disorder among older adults. The disorder has a pervasive influence on the lives of those affected, and is a risk factor for other severe disorders such as depression, dementia and coronary heart disease. Cognitive behaviour therapy (CBT) is the treatment of choice for this disorder, but older adults have shown reduced effect of treatment compared to working age adults. Physical exercise has been suggested as intervention to improve the effects of treatment for GAD, via its demonstrated positive effect on cognitive functioning, increased plasticity in the brain, and increased availability of neurotrophins important for extinction of fear associations. The aim of the current research project is to investigate whether augmenting CBT with physical exercise will lead to improved effects of CBT on GAD in older adults in a randomized controlled trial (RCT). Participants between 60-75 years of age with a primary diagnosis of GAD will be randomised to one of two treatment conditions. The effects of treatment will be assessed on outcome measures, biological, physiological and cognitive measures at pre- interim-, and post-treatment, and follow-up assessments at 6- and 12-months post intervention. Participants in both groups will receive five weeks of pre-treatment intervention consisting of either physical exercise or weekly telephone contact. Participants thereafter receive either ten weeks of manualised CBT for GAD combined with manualised physical exercise or ten weeks of manualised CBT for GAD combined with weekly telephone contact. We expect that the treatment effect of the physical exercise augmented CBT will be greater than that of CBT combined with weekly telephone contact, as measured by a reduction in GAD symptoms on the Penn State Worry Questionnaire and in the proportion of remitted patients. The study also aims to determining the possible beneficial and augmenting properties of physical exercise in combination with CBT, and our understanding of clinical characteristics of GAD and mechanisms involved in treatment effect. Treatment rationale, procedures and protocols will be presented in detail together with preliminary results from the initial feasibility study comprises eight participants.
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| 22. |
- Specht, Ina Olmer, et al.
(författare)
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Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 66:Feb 26, s. 146-156
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones.
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| 23. |
- Specht, Ina O., et al.
(författare)
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Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics
- 2012
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Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 14:6, s. 890-896
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis in the testis has two putative roles during normal spermatogenesis; limitation of the germ cell population to numbers that can be supported by the Sertoli cells, and, possibly, selective depletion of meiotic and postmeiotic abnormal germ cells. We investigated the demographic and biological correlates of the pro-apoptotic marker Fas and the anti-apoptotic marker Bcl-xL in sperm cells of fertile men. Six hundred and four men from Greenland, Poland and Ukraine were consecutively enrolled during their pregnant wife's antenatal visits. Semen analysis was performed as recommended by the World Health Organization. Immunofluorescence coupled to flow cytometry was utilized for detection of apoptotic markers in the sperm cell. DNA damage was assessed by flow cytometry using both the sperm chromatin structure assay (SCSA) and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. The percentage of Fas-positive sperm cells was higher in men with high total sperm count (P<0.01), more motile sperms (P=0.04) and fewer sperm head defects (P=0.05). These associations were consistent within and across study regions. Furthermore, testosterone, follicle-stimulating hormone (FSH) and sexual hormone-binding globulin (SHBG) were significantly negatively correlated with Fas within and across regions as well. The data indicated no association between the anti-apoptotic Bcl-xL marker and semen or personal characteristics. The finding of Fas-positive sperm cells associated with better semen quality in a cohort of spouses of pregnant women seems different from previous data obtained in infertile men and warrants further investigation to clarify the biological significance of sperm apoptotic markers. Asian Journal of Andrology (2012) 14, 890-896; doi: 10.1038/aja.2012.76; published online 15 October 2012
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| 24. |
- Specht, Ina Olmer, et al.
(författare)
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Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances - A study of spouses of pregnant women in three geographical regions
- 2012
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 33:4, s. 577-583
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFASs) can interfere with male reproductive function, but evidence in humans is limited. Six hundred four fertile men (199 from Greenland, 197 from Poland and 208 from Ukraine) were enrolled in the study. We measured four PFASs in serum (PFOS, PFOA, PFNA and PFHxS) and concurrent DNA damage in spermatozoa by sperm chromatin structure assay (SCSA) and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, apoptotic markers in semen (Fas-receptor and Bcl-xL), and reproductive hormones in serum. No association between PFASs and SCSA, apoptotic markers or reproductive hormones emerged. We observed a slight increase in SHBG and TUNEL-positivity with increased PFOA exposure in men from Greenland. Thus, consistent evidence that PFAS exposure interferes with sperm DNA fragmentation, apoptosis or reproductive hormones was not found. (C) 2012 Elsevier Inc. All rights reserved.
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