| 1. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 2. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 3. |
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| 4. |
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| 5. |
- Duffy, J. M. N., et al.
(författare)
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Developing a core outcome set for future infertility research: an international consensus development study
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2725-2734
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set.
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| 6. |
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| 7. |
- Duffy, J. M. N., et al.
(författare)
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Top 10 priorities for future infertility research: an international consensus development study
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2715-2724
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from I I countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda.
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| 8. |
- Duffy, J. M. N., et al.
(författare)
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Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study
- 2020
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2735-2745
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set.
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| 9. |
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| 10. |
- Preis, S, et al.
(författare)
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Munich atopy prediction study (MAPS): protocol for a prospective birth cohort addressing clinical and molecular risk factors for atopic dermatitis in early childhood
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e059256-
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an interdependent network of components of skin development in young age and skin barrier dysfunction underlying AD development that is only partially understood, a complex interplay between environmental factors and lifestyle habits with skin barrier and immune dysregulation is suspected to contribute to AD onset. This study aims to comprehensively evaluate individual microbiome and immune responses in the context of environmental determinants related the risk of developing AD in the first 4 years of a child’s life.Methods and analysesThe ‘Munich Atopic Prediction Study’ is a comprehensive clinical and biological investigation of a prospective birth cohort from Munich, Germany. Information on pregnancy, child development, environmental factors, parental exposures to potential allergens and acute or chronic diseases of children and parents are collected by questionnaires together with a meticulous clinical examination by trained dermatologists focusing on allergies, skin health, and in particular signs of AD at 2 months after birth and then every 6 months. In addition, skin barrier functions are assessed through cutometry, corneometry and transepidermal water loss at every visit. These measurements are completed with allergy diagnostics and extensive microbiome analyses from stool and skin swabs as well as transcriptome analyses using skin microbiopsies.The aim is to assess the relevance of different known and yet unknown risk factors of AD onset and exacerbations in infants and to identify possible accessible and robust biomarkers.Ethics and disseminationThe study is approved by the Ethical Committee of the Medical Faculty of the Technical University of Munich (reference 334/16S). All relevant study results will be presented at national and international conferences and in peer-reviewed journals.
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| 11. |
- Roelfsema, P. R., et al.
(författare)
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SPICA-A Large Cryogenic Infrared Space Telescope : Unveiling the Obscured Universe
- 2018
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Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity. SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope. cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions. SPICA instruments offer spectral resolving power ranging from R similar to 50 through 11 000 in the 17-230 mu m domain and R similar to 28.000 spectroscopy between 12 and 18 mu m.SPICA will provide efficient 30-37 mu m broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 mu m. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of similar to 5 x 10(-20) W m (-2) (5 sigma/1 h)-over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
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| 12. |
- Ständer, Sonja, et al.
(författare)
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IFSI-Guideline on Chronic Prurigo including Prurigo nodularis.
- 2020
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Ingår i: ITCH. - : Ovid Technologies (Wolters Kluwer Health). - 2380-5048. ; 5:4, s. 1-13
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Forskningsöversikt (refereegranskat)abstract
- Chronic prurigo (CPG) is a highly burdensome pruritic disease characterized by chronic itch, a prolonged scratching behavior and the development of localized or generalized hyperkeratotic pruriginous lesions. Neuronal sensitization and the development of an itch-scratch cycle contribute to the augmentation of pruritus and the chronicity of the disease. We provide here the first international guideline for a rational diagnostic and therapeutic approach for CPG. Recommendations are based on available evidence and expert opinion. The diagnosis of CPG is made clinically. A detailed medical history together with laboratory and radiological examinations are advised in order to determine the severity of CPG, identify the underlying origin of the itch and assist in the elaboration of a treatment plan. Therapeutically, it is advised to adopt a multimodal approach, including general strategies to control itch, treatment of the underlying pruritic conditions, and of the pruriginous lesions. Topical (corticosteroids, calcineurin inhibitors, capsaicin) and systemic antipruritic agents (eg, gabapentinoids, immunosuppressants, and opioid modulators) as well as physical treatment modalities (phototherapy, cryotherapy) should be employed in a step-wise approach. Psychosomatic or psychological interventions may be recommended in CPG patients with signs of psychiatric/psychological comorbidities.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Pereira, Manuel P., et al.
(författare)
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Google search trends for itch in Europe : a retrospective longitudinal study
- 2021
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Ingår i: Journal of the European Academy of Dermatology and Venereology : JEADV. - : Wiley. - 1468-3083 .- 0926-9959. ; 35:6, s. 1362-1370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Itch is a common symptom in the general population. Affected individuals often do not seek medical consultation and rely on Internet searches to obtain information regarding their itch.OBJECTIVES: The aim of this study was to attain insights into common concerns of the general population regarding itch can by analysing itch-related Internet search behaviour.METHODS: Google AdWords Keyword Planner was used to assess search volumes for itch-related terms in 15 European countries between September 2014 and August 2018. All identified keywords were qualitatively categorized. Itch-related terms were descriptively analysed and are shown as number of searches/100 000 inhabitants.RESULTS: The search volume for the keyword 'itch' per 100 000 inhabitants was highest in Northern Europe, followed by Eastern, Central and Southern Europe. In 4/15 countries, itch was searched for more often in the autumn/winter months compared to in the spring/summer months. Most itch-related terms were related to dermatological conditions such as inflammatory skin diseases (e.g. psoriasis, atopic dermatitis), allergic or immunologic conditions (e.g. urticaria), and infectious diseases or infestations (e.g. scabies). In terms of body location, genitoanal itch dominated the searches. Symptoms and signs related to itch, possible non-dermatological aetiologies, and treatment options were also among the most searched terms.CONCLUSIONS: These analyses provided for the first time insights into the search behaviour patterns related to itch across Europe. People from Northern and Eastern Europe are more likely to seek online information regarding itch. Causes for the itch, especially dermatological conditions, and genitoanal itch are the most important concerns for Internet users. This unconventional and inexpensive method identifies medical needs of people beyond the medical setting, including people who do not seek medical consultation. Accordingly, the data could be used to guide public health interventions and manage respective inhabitants' medical needs.
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| 17. |
- Pereira, M. P., et al.
(författare)
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Position Statement : Linear prurigo is a subtype of chronic prurigo
- 2019
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 33:2, s. 263-266
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG. Objective: To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature. Methods: Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement. Results: Twenty-one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term ‘linear prurigo’ was chosen to describe this manifestation. Conclusion: Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self-inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo.
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| 18. |
- Glasier, A, et al.
(författare)
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Contraception after pregnancy
- 2019
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 98:11, s. 1378-1385
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Tidskriftsartikel (refereegranskat)
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| 19. |
- Khuyagbaatar, J., et al.
(författare)
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48Ca+249Bk Fusion Reaction Leading to Element Z=117: Long-Lived α-Decaying 270Db and Discovery of 266Lr
- 2014
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Ingår i: Physical Review Letters. - 1079-7114. ; 112:17
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Tidskriftsartikel (refereegranskat)abstract
- The superheavy element with atomic number Z=117 was produced as an evaporation residue in the 48Ca+249Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope 294-117 and its decay products. A hitherto unknown α-decay branch in 270Db (Z=105) was observed, which populated the new isotope 266Lr (Z=103). The identification of the long-lived (T1/2=1.0+1.9−0.4 h) α-emitter 270Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an “island of stability.”
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| 20. |
- Khuyagbaatar, J., et al.
(författare)
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Fusion reaction 48Ca + 249Bk leading to formation of the element Ts (Z=117)
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- The heaviest currently known nuclei, which have up to 118 protons, have been produced in 48Ca induced reactions with actinide targets. Among them, the element tennessine (Ts), which has 117 protons, has been synthesized by fusing 48Ca with the radioactive target 249Bk, which has a half-life of 327 d. The experiment was performed at the gas-filled recoil separator TASCA. Two long and two short α decay chains were observed. The long chains were attributed to the decay of 294Ts. The possible origin of the short-decay chains is discussed in comparison with the known experimental data. They are found to fit with the decay chain patterns attributed to 293Ts. The present experimental results confirm the previous findings at the Dubna Gas-Filled Recoil Separator on the decay chains originating from the nuclei assigned to Ts.
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| 21. |
- Khuyagbaatar, J., et al.
(författare)
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Search for elements 119 and 120
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 102:6
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Tidskriftsartikel (refereegranskat)abstract
- A search for production of the superheavy elements with atomic numbers 119 and 120 was performed in the 50Ti+249Bk and 50Ti+249Cf fusion-evaporation reactions, respectively, at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. Over four months of irradiation, the 249Bk target partially decayed into 249Cf, which allowed for a simultaneous search for both elements. Neither was detected at cross-section sensitivity levels of 65 and 200 fb for the 50Ti+249Bk and 50Ti+249Cf reactions, respectively, at a midtarget beam energy of Elab = 281.5 MeV. The nonobservation of elements 119 and 120 is discussed within the concept of fusion-evaporation reactions including various theoretical predictions on the fission-barrier heights of superheavy nuclei in the region of the island of stability.
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| 22. |
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| 23. |
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| 24. |
- Ständer, S., et al.
(författare)
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EADV Task Force Pruritus White Paper on chronic pruritus and chronic prurigo : Current challenges and future solutions
- 2024
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - 0926-9959 .- 1468-3083.
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.
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| 25. |
- Ständer, S, et al.
(författare)
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European EADV network on assessment of severity and burden of Pruritus (PruNet): first meeting on outcome tools.
- 2015
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 30:7, s. 1144-1147
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pruritus is a frequently occurring symptom of various dermatoses that causes a high burden and impaired quality of life. An effective anti pruritic therapy is important for the patient, but its effectiveness is difficult to evaluate. Diverse methods and interpretations of pruritic metrics are utilized in clinical trials and the daily clinical practice in different countries, resulting in difficulties comparing collected data.
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| 26. |
- Araujo, Nathalia, et al.
(författare)
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Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.
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| 27. |
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| 28. |
- Collins, J, et al.
(författare)
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Genetic aspects of female reproduction
- 2008
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Ingår i: Human reproduction update. - : Oxford University Press (OUP). - 1460-2369 .- 1355-4786. ; 14:4, s. 293-307
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Tidskriftsartikel (refereegranskat)
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Li, Jing, et al.
(författare)
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An obligatory role for neurotensin in high-fat-diet-induced obesity
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533, s. 411-415
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and released by fat ingestion, facilitates fatty acid translocation in rat intestine, and stimulates the growth of various cancers. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.
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| 33. |
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| 34. |
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| 35. |
- Sampogna, Francesca, et al.
(författare)
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Measuring the impact of dermatological conditions on family and caregivers : a review of dermatology-specific instruments
- 2017
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959. ; 31:9, s. 1429-1439
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Forskningsöversikt (refereegranskat)abstract
- The patient is the centre of a web of relationships, and the impact of his/her disease on family members and caregivers must be taken into account. The aim of this study was to identify the specific instruments that measure the impact of a dermatological disease on the quality of life (QoL) of family members, by performing a systematic search of the literature. Fifteen papers were identified, describing the creation and validation of nine instruments. Four of them concerned atopic dermatitis (Dermatitis Family Index, DFI; Parents’ Index QoL Atopic Dermatitis, PiQoL-AD; QoL in primary caregivers of children with atopic dermatitis, QPCAD; Childhood Atopic Dermatitis Impact Scale, CADIS), two measured the impact of psoriasis in family members (Psoriasis Family Index, PFI; FamilyPso), one the impact of epidermolysis bullosa (Epidermolysis Bullosa Burden of Disease, EB-BoD), one of ichthyosis (Family Burden Ichthyosis, FBI), and one was generic for dermatological conditions (Family Dermatology Life Quality Index, FDLQI). The European Academy of Dermatology and Venereology quality of life taskforce recommends that the impact of a skin disease on family and caregivers should be measured as part of any thorough evaluation of the burden of a disease. Guidelines are given to choose the most appropriate instruments.
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| 36. |
- Scholz, Joachim, et al.
(författare)
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The IASP classification of chronic pain for ICD-11 : chronic neuropathic pain.
- 2019
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 160:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.
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| 37. |
- Abeysinghe, Kasun S., et al.
(författare)
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Mercury flow through an Asian rice-based food web
- 2017
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Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 229, s. 219-228
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a globally-distributed pollutant, toxic to humans and animals. Emissions are particularly high in Asia, and the source of exposure for humans there may also be different from other regions, including rice as well as fish consumption, particularly in contaminated areas. Yet the threats Asian wildlife face in rice-based ecosystems are as yet unclear. We sought to understand how Hg flows through rice-based food webs in historic mining and non-mining regions of Guizhou, China. We measured total Hg (THg) and methylmercury (MeHg) in soil, rice, 38 animal species (27 for MeHg) spanning multiple trophic levels, and examined the relationship between stable isotopes and Hg concentrations. Our results confirm biomagnification of THg/MeHg, with a high trophic magnification slope. Invertivorous songbirds had concentrations of THg in their feathers that were 15x and 3x the concentration reported to significantly impair reproduction, at mining and non-mining sites, respectively. High concentrations in specialist rice consumers and in granivorous birds, the later as high as in piscivorous birds,, suggest rice is a primary source of exposure. Spiders had the highest THg concentrations among invertebrates and may represent a vector through which Hg is passed to vertebrates, especially songbirds. Our findings suggest there could be significant population level health effects and consequent biodiversity loss in sensitive ecosystems, like agricultural wetlands, across Asia, and invertivorous songbirds would be good subjects for further studies investigating this possibility.
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| 38. |
- Aghajanova, Lusine, et al.
(författare)
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No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility
- 2015
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 30:1, s. 232-238
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility?SUMMARY ANSWER: We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.WHAT IS KNOWN ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).MAIN RESULTS AND THE ROLE OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.LIMITATIONS, REASONS FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.WIDER IMPLICATIONS OF THE FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.STUDY FUNDING/COMPETING INTERESTS: This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.
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| 39. |
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| 40. |
- Aghajanova, L., et al.
(författare)
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Stanniocalcin-1 in Human Endometrium
- 2015
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Ingår i: Fertility and Sterility. - 0015-0282 .- 1556-5653. ; 103:2, s. E6-E7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Altmäe, Signe, et al.
(författare)
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Guidelines for the design, analysis and interpretation of 'omics' data : focus on human endometrium
- 2013
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Ingår i: Human Reproduction Update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 20:1, s. 12-28
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.
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| 48. |
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| 49. |
- Baird, DT, et al.
(författare)
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Nutrition and reproduction in women
- 2006
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Ingår i: Human reproduction update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 12:3, s. 193-207
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Tidskriftsartikel (refereegranskat)
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| 50. |
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