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- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 2. |
- Regev, A, et al.
(författare)
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The Human Cell Atlas
- 2017
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Ingår i: eLife. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Rozenblatt-Rosen, O., et al.
(författare)
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Building a high-quality Human Cell Atlas
- 2021
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Ingår i: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 39:2, s. 149-153
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Borge, C. R., et al.
(författare)
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Effects of guided deep breathing on breathlessness and the breathing pattern in chronic obstructive pulmonary disease: A double-blind randomized control study
- 2015
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Ingår i: Patient Education and Counseling. - : Elsevier BV. - 0738-3991 .- 1873-5134. ; 98:2, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether guided deep breathing using a device improves breathlessness, quality of life, and breathing pattern in moderate and severe stage of chronic obstructive pulmonary disease (COPD). METHODS: In total, 150 patients participated in a double-blind randomized controlled trial in a four-week intervention and a four-month follow-up. Participants were randomized into a guided deep breathing group (GDBG), music listening group (MLG), or sitting still group (SSG). The patients' symptom score using the St George's Respiratory Questionnaire (SGRQ), and a Global Rating Change scale (GRC) was applied to measure breathlessness as primary outcome. The activity score and impact score of SRGQ, and breathing pattern were secondary outcomes. RESULTS: Positive effects of the GDBG were detected in GRC scale in breathlessness at four weeks (p=0.03) with remaining effect compared to MLG (p=0.04), but not to SSG at four months follow-up. GDBG showed positive effect for respiratory rate (p<0.001) at four weeks follow-up. A positive significant change (p<0.05-0.01) was found in all groups of SGRQ symptom score. CONCLUSION: GDBG had a beneficial effect on respiratory pattern and breathlessness. MLG and SSG also yielded significant improvements. PRACTICE IMPLICATIONS: Guided deep breathing may be used as a self-management procedure.
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| 11. |
- Hochgerner, H, et al.
(författare)
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STRT-seq-2i: dual-index 5' single cell and nucleus RNA-seq on an addressable microwell array
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 16327-
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell RNA-seq has become routine for discovering cell types and revealing cellular diversity, but archived human brain samples still pose a challenge to current high-throughput platforms. We present STRT-seq-2i, an addressable 9600-microwell array platform, combining sampling by limiting dilution or FACS, with imaging and high throughput at competitive cost. We applied the platform to fresh single mouse cortical cells and to frozen post-mortem human cortical nuclei, matching the performance of a previous lower-throughput platform while retaining a high degree of flexibility, potentially also for other high-throughput applications.
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| 12. |
- Hu, M., et al.
(författare)
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Variability in larval gut pH regulation defines sensitivity to ocean acidification in six species of the ambulacraria superphylum
- 2017
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1864
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Tidskriftsartikel (refereegranskat)abstract
- The unusual rate and extent of environmental changes due to human activities may exceed the capacity of marine organisms to deal with this phenomenon. The identification of physiological systems that set the tolerance limits and their potential for phenotypic buffering in the most vulnerable ontogenetic stages become increasingly important to make large-scale projections. Here, we demonstrate that the differential sensitivity of non-calcifyingAmbulacraria (echinoderms and hemichordates) larvae towards simulated ocean acidification is dictated by the physiology of their digestive systems. Gastric pH regulation upon experimental ocean acidification was compared in six species of the superphylum Ambulacraria.We observed a strong correlation between sensitivity to ocean acidification and the ability to regulate gut pH. Surprisingly, species with tightly regulated gastric pH were more sensitive to ocean acidification. This study provides evidence that strict maintenance of highly alkaline conditions in the larval gut of Ambulacraria early life stages may dictate their sensitivity to decreases in seawater pH. These findings highlight the importance of identifying and understanding pH regulatory systems in marine larval stages that may contribute to substantial energetic challenges under near-future ocean acidification scenarios. © 2017 The Author(s) Published by the Royal Society. All rights reserved.
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| 15. |
- Lein, E, et al.
(författare)
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The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing
- 2017
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 358:6359, s. 64-
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Tidskriftsartikel (refereegranskat)abstract
- The stereotyped spatial architecture of the brain is both beautiful and fundamentally related to its function, extending from gross morphology to individual neuron types, where soma position, dendritic architecture, and axonal projections determine their roles in functional circuitry. Our understanding of the cell types that make up the brain is rapidly accelerating, driven in particular by recent advances in single-cell transcriptomics. However, understanding brain function, development, and disease will require linking molecular cell types to morphological, physiological, and behavioral correlates. Emerging spatially resolved transcriptomic methods promise to fill this gap by localizing molecularly defined cell types in tissues, with simultaneous detection of morphology, activity, or connectivity. Here, we review the requirements for spatial transcriptomic methods toward these goals, consider the challenges ahead, and describe promising applications.
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| 20. |
- Taule, T., et al.
(författare)
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Psychometric Properties of Cognitive Assessment in Amyotrophic Lateral Sclerosis: A Systematic Review
- 2020
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Ingår i: Patient-Related Outcome Measures. - 1179-271X. ; 11, s. 181-194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We aimed to list all tests used to assess cognitive change in patients with amyotrophic lateral sclerosis (ALS) and to provide a descriptive synthesis of the psychometric properties of tests that were evaluated in a population of ALS patients. Materials and Methods: The protocol is registered in PROSPERO (ID: CRD42017055603). We systematically search for literature in 11 databases. Full-text articles, in any language, with original research were included. All included articles were scrutinised by two independent authors. Disagreement was resolved by consensus. The framework of Lezak informed conceptualises of the tests identified. To evaluate methodological quality, we used the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN). Data were synthesised using criteria proposed by the Cochrane Back Review Group. Results: Of 319 included articles, 46 articles reported information on the psychometric properties of cognitive tests used in patients with ALS. We found that the highest level of evidence was supported for the Reading the Mind in the Eye Test (RME), Addenbrooke's Cognitive Evaluation (ACE) and Frontal Assessment Battery (FAB). Moderate level of evidence was found for the screening tests; Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and the Montreal Cognitive Assessment (MoCA). Conclusion: The screening test, ECAS and the social cognition test, RME, may have some advantages over other tests that have been used for assessing cognitive change in ALS patients. Recommendations of ALS-specific tests with sound psychometric properties are urgently needed.
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| 22. |
- Wegwarth, O, et al.
(författare)
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What do European women know about their female cancer risks and cancer screening? A cross-sectional online intervention survey in five European countries
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:12, s. e023789-
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Tidskriftsartikel (refereegranskat)abstract
- Informed decisions about cancer screening require accurate knowledge regarding cancer risks and screening. This study investigates: (1) European women’s knowledge of their risk of developing breast, ovarian, cervical or endometrial cancer, (2) their knowledge about mammography screening and (3) whether an evidence-based leaflet improves their knowledge.DesignCross-sectional online intervention survey.SettingNational samples from five European countries (Czech Republic, Germany, UK, Italy and Sweden)—drawn from the Harris Interactive and the Toluna panel, respectively, in January 2017—were queried on their knowledge of age-specific risks of developing breast, cervical, ovarian or endometrial cancer within the next 10 years and of mammography screening before and after intervention.ParticipantsOf 3629 women (inclusion criteria: age 40–75 years) invited, 2092 responded and 1675 completed the survey (response rate: 61.4%).InterventionEvidence-based leaflet summarising information on age-adjusted female cancer risks, mammography and aspects of cancer prevention.Primary outcome measuresProportion of women (1) accurately estimating their risk of four female cancers, (2) holding correct assumptions of mammography screening and (3) changing their estimations and assumptions after exposure to leaflet.FindingsAcross countries, 59.2% (95% CI 56.8% to 61.6%) to 91.8% (95% CI 90.3% to 93.0%) overestimated their female cancer risks 7–33 fold (mediansacross tumours: 50.0 to 200.0). 26.5% (95% CI 24.4% to 28.7%) were aware that mammography screening has both benefits and harms. Women who accurately estimated their breast cancer risk were less likely to believe that mammography prevents cancer (p<0.001). After leaflet intervention, knowledge of cancer risks improved by 27.0 (95% CI 24.9 to 29.2) to 37.1 (95% CI 34.8 to 39.4) percentage points and of mammography by 23.0 (95% CI 21.0 to 25.1) percentage points.ConclusionA considerable number of women in five European countries may not possess the prerequisites for an informed choice on cancer screening. Evidence-based information in patient leaflets can improve this situation.
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