| 1. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Alimena, Juliette, et al.
(author)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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In: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Journal article (peer-reviewed)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 3. |
- Engert, Andreas, et al.
(author)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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In: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Journal article (peer-reviewed)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 4. |
- Rieke, Johanna Magdalena, et al.
(author)
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SLC20A1Is Involved in Urinary Tract and Urorectal Development
- 2020
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In: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
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Journal article (peer-reviewed)abstract
- Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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| 5. |
- Bengtsson, Ewert, 1948-, et al.
(author)
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Detection of Malignancy-Associated Changes Due to Precancerous and Oral Cancer Lesions: A Pilot Study Using Deep Learning
- 2018
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In: CYTO2018.
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Conference paper (peer-reviewed)abstract
- Background: The incidence of oral cancer is increasing and it is effecting younger individuals. PAP smear-based screening, visual, and automated, have been used for decades, to successfully decrease the incidence of cervical cancer. Can similar methods be used for oral cancer screening? We have carried out a pilot study using neural networks for classifying cells, both from cervical cancer and oral cancer patients. The results which were reported from a technical point of view at the 2017 IEEE International Conference on Computer Vision Workshop (ICCVW), were particularly interesting for the oral cancer cases, and we are currently collecting and analyzing samples from more patients. Methods: Samples were collected with a brush in the oral cavity and smeared on glass slides, stained, and prepared, according to standard PAP procedures. Images from the slides were digitized with a 0.35 micron pixel size, using focus stacks with 15 levels 0.4 micron apart. Between 245 and 2,123 cell nuclei were manually selected for analysis for each of 14 datasets, usually 2 datasets for each of the 6 cases, in total around 15,000 cells. A small region was cropped around each nucleus, and the best 2 adjacent focus layers in each direction were automatically found, thus creating images of 100x100x5 pixels. Nuclei were chosen with an aim to select well preserved free-lying cells, with no effort to specifically select diagnostic cells. We therefore had no ground truth on the cellular level, only on the patient level. Subsets of these images were used for training 2 sets of neural networks, created according to the ResNet and VGG architectures described in literature, to distinguish between cells from healthy persons, and those with precancerous lesions. The datasets were augmented through mirroring and 90 degrees rotations. The resulting networks were used to classify subsets of cells from different persons, than those in the training sets. This was repeated for a total of 5 folds. Results: The results were expressed as the percentage of cell nuclei that the neural networks indicated as positive. The percentage of positive cells from healthy persons was in the range 8% to 38%. The percentage of positive cells collected near the lesions was in the range 31% to 96%. The percentages from the healthy side of the oral cavity of patients with lesions ranged 37% to 89%. For each fold, it was possible to find a threshold for the number of positive cells that would correctly classify all patients as normal or positive, even for the samples taken from the healthy side of the oral cavity. The network based on the ResNet architecture showed slightly better performance than the VGG-based one. Conclusion: Our small pilot study indicates that malignancyassociated changes that can be detected by neural networks may exist among cells in the oral cavity of patients with precancerous lesions. We are currently collecting samples from more patients, and will present those results as well, with our poster at CYTO 2018.
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| 6. |
- Blomstrand, Lena, et al.
(author)
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Telemedicine : a complement to traditional referrals in oral medicine
- 2012
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In: Telemedicine journal and e-health. - : Mary Ann Liebert Inc. - 1530-5627 .- 1556-3669. ; 18:7, s. 549-553
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Journal article (peer-reviewed)abstract
- Introduction:Introducing telemedicine into clinical practice has not been without difficulties. Within the framework of the European Union project "Health Optimum," telemedicine consultations with specialists at the Department of Oral & Maxillofacial Surgery at Uppsala University Hospital (Uppsala, Sweden) have been offered to dentists in the public dental health service. The aim is to streamline the consultation process, improve/develop the skills of the participating dentists and dental hygienists, and save time and money for patients, healthcare authorities, and society.Subjects and Methods:Patient records are collected in a database for demonstration and discussion, and the system is also available for referrals. Both medical and dental photographs and x-rays are digitized in the same system. These can be viewed during telemedicine rounds and by the consultants at the hospital prior to a consultation. Secure, interactive conferencing software is used, which provides a quick, easy, and effective way to share video and data over the Internet. Both parties can demonstrate different parts of an image using a pointer or a drawing system. Conference phones are presently used for verbal communication.Results:Ten patients were discussed during telemedicine rounds (3 males and 7 females), all of whom would normally have been referred to a specialist. As a result of the telemedicine round, 2 were referred to a specialist, whereas diagnoses were made for the other 8, and treatment was suggested. The dental health clinic could thus provide treatment without the need for referral to a consultant.Conclusions:The telemedicine system described here allows patient care to be provided rapidly and more economically. Future plans include "live" rounds using a videocamera, providing the possibility to relay real-time information about the intraoral situation. A camera is being developed and should preferably be permanently installed chair side.
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| 7. |
- Dérand, Per, et al.
(author)
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Virtual bending of mandibular reconstruction plates using a computer-aided design
- 2009
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In: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 67:8, s. 1640-1643
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Journal article (peer-reviewed)abstract
- PURPOSE: The purpose of this study was to investigate the possibility of virtually designing and manufacturing a template for reconstruction plate bending, to be used during treatment of congenital or acquired bony entities. The outcome was compared with plates bent by the freehand approach in a stereolithographic skull model. MATERIALS AND METHODS: From a computed tomography examination, a polygon skull was created and the corresponding stereolithographic model retrieved. A polygon mesh of a Compact UniLock 2.4-mm plate was obtained from Synthes (Bettlach, Switzerland). The polygon plate was bent virtually around the mandible and rendered in all 3 dimensions, and a template was created. Five 10-hole plates were bent using this template, and five 10-hole plates were bent using a stereolithographic model as the template. The 2 groups were compared using the Wilcoxon signed rank test. P values less than .001 was considered to be statistically significant. RESULTS: No statistical difference was seen between the 2 methods. The median discrepancy between the 2 groups was 0.1 mm. CONCLUSION: Within the constraints of this investigation, by use of a virtually produced template based on a virtually planned reconstruction, it is possible to bend a reconstruction plate with the same degree of accuracy as that of the traditional freehand approach.
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| 8. |
- Edman, Kristina, 1958-, et al.
(author)
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Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening
- 2023
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In: International Journal of Dental Hygiene. - : John Wiley & Sons. - 1601-5029 .- 1601-5037. ; 21:3, s. 524-532
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Journal article (peer-reviewed)abstract
- BackgroundOral cancer is a severe and potentially fatal disease usually starting in the squamous epithelium lining the oral cavity. Together with oropharyngeal carcinoma, it is the fifth to sixth most common malignancy worldwide. To limit the increase in the global oral cancer incidence over the past two decades, the World Health Assembly adopted a resolution urging member states to integrate preventive measures such as engagement and training of dental personnel in screening, early diagnosis, and treatment into their national cancer control programs.AimThe aim of this study was to investigate if dental hygienists (DHs) and dentists (Ds) in general dental practice care can be entrusted to perform brush sampling of oral potentially malignant disorders (OPMDs), and to evaluate their level of comfort in performing brush biopsies.MethodsParticipants were five DHs and five Ds who received one day of theoretical and clinical training in oral pathology to identify OPMDs (leukoplakia [LP], erythroplakia [EP], and oral lichen planus [OLP]), and perform brush sampling for PAP cytology and high-risk human papillomavirus (hrHPV) analysis.ResultsOut of 222 collected samples, 215 were adequate for morphological assessment and hrHPV analysis. All the participants agreed that sample collection can be incorporated in DHs and Ds routine clinical duties, and most of them reported that sample collection and processing was easy/quite easy.ConclusionDentists and DHs are capable of collecting satisfactory material for cytology and hrHPV analysis. All the participating DHs and Ds were of the opinion that brush sampling could be handled routinely by DHs and Ds in GDP.
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| 9. |
- Farzad, Payam, et al.
(author)
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Högteknologi revolutionerar kraniomaxillofacial kirurgi : Datornavigation ger bättre precision och färre komplikationer
- 2009
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:38, s. 2362-2365
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Journal article (peer-reviewed)abstract
- Inom kraniofacial kirurgi pågår en högteknologisk utveckling. Datorstödd och datornavigerad kirurgi är områden som i dag utvecklas snabbt. Nyttan med dessa teknologier är framför allt förbättrad precision och förutsägbarhet med minskad risk för komplikationer och totalt mindre morbiditet. Virtuell planering av rekonstruktioner kan nu göras i och med att datortomografin utvecklats från analog till digital teknik. En ideal simulering av det tilltänkta ingreppet görs sedan på en datorarbetsstation. Osteotomier, förflyttningar av bensegment eller inpassning av biomaterial kan simuleras oändligt antal gånger. Med hjälp av individuellt producerade guider i stereolitografi eller med en navigator överförs den virtuella planen till operationssituationen.
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| 10. |
- Haj-Hosseini, Neda, 1980-, et al.
(author)
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Early Detection of Oral Potentially Malignant Disorders: A Review on Prospective Screening Methods with Regard to Global Challenges
- 2024
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In: Journal of Maxillofacial & Oral Surgery. - New Delhi, India : Springer Science and Business Media LLC. - 0972-8279 .- 0974-942X. ; 23:1, s. 23-32
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Journal article (peer-reviewed)abstract
- Oral cancer is a cancer type that is widely prevalent in low-and middle-income countries with a high mortality rate, and poor quality of life for patients after treatment. Early treatment of cancer increases patient survival, improves quality of life and results in less morbidity and a better prognosis. To reach this goal, early detection of malignancies using technologies that can be used in remote and low resource areas is desirable. Such technologies should be affordable, accurate, and easy to use and interpret. This review surveys different technologies that have the potentials of implementation in primary health and general dental practice, considering global perspectives and with a focus on the population in India, where oral cancer is highly prevalent. The technologies reviewed include both sample-based methods, such as saliva and blood analysis and brush biopsy, and more direct screening of the oral cavity including fluorescence, Raman techniques, and optical coherence tomography. Digitalisation, followed by automated artificial intelligence based analysis, are key elements in facilitating wide access to these technologies, to non-specialist personnel and in rural areas, increasing quality and objectivity of the analysis while simultaneously reducing the labour and need for highly trained specialists.
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