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- Kvedaraite, E, et al.
(författare)
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Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
- 2022
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330-
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Tidskriftsartikel (refereegranskat)abstract
- Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
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- Davies, Stuart J., et al.
(författare)
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ForestGEO: Understanding forest diversity and dynamics through a global observatory network
- 2021
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 253
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Tidskriftsartikel (refereegranskat)abstract
- ForestGEO is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types. ForestGEO's mission is to advance understanding of the diversity and dynamics of forests and to strengthen global capacity for forest science research. ForestGEO is unique among forest plot networks in its large-scale plot dimensions, censusing of all stems ≥1 cm in diameter, inclusion of tropical, temperate and boreal forests, and investigation of additional biotic (e.g., arthropods) and abiotic (e.g., soils) drivers, which together provide a holistic view of forest functioning. The 71 FDPs in 27 countries include approximately 7.33 million living trees and about 12,000 species, representing 20% of the world's known tree diversity. With >1300 published papers, ForestGEO researchers have made significant contributions in two fundamental areas: species coexistence and diversity, and ecosystem functioning. Specifically, defining the major biotic and abiotic controls on the distribution and coexistence of species and functional types and on variation in species' demography has led to improved understanding of how the multiple dimensions of forest diversity are structured across space and time and how this diversity relates to the processes controlling the role of forests in the Earth system. Nevertheless, knowledge gaps remain that impede our ability to predict how forest diversity and function will respond to climate change and other stressors. Meeting these global research challenges requires major advances in standardizing taxonomy of tropical species, resolving the main drivers of forest dynamics, and integrating plot-based ground and remote sensing observations to scale up estimates of forest diversity and function, coupled with improved predictive models. However, they cannot be met without greater financial commitment to sustain the long-term research of ForestGEO and other forest plot networks, greatly expanded scientific capacity across the world's forested nations, and increased collaboration and integration among research networks and disciplines addressing forest science.
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- Zhang, Yingyang, et al.
(författare)
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Association of Comorbidity With Healthcare Utilization in People Living With Dementia, 2010–2019 : A Population-Based Cohort Study
- 2023
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Ingår i: Dementia. - 1471-3012 .- 1741-2684.
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Tidskriftsartikel (refereegranskat)abstract
- Evidence on the healthcare utilization associated with comorbidity in people with dementia is lacking in Chinese societies. This study aimed to quantify healthcare utilization associated with comorbidity that is common in people living with dementia. We conducted a cohort study using population-based data from Hong Kong public hospitals. Individuals aged 35+ with a dementia diagnosis between 2010 and 2019 were included. Among 88,151 participants, people with at least two comorbidities accounted for 81.2%. Estimates from negative binomial regressions showed that compared to those with one or no comorbid condition other than dementia, adjusted rate ratios of hospitalizations among individuals with six or seven and eight or more conditions were 1.97 [98.75% CI, 1.89–2.05] and 2.74 [2.63–2.86], respectively; adjusted rate ratios of Accident and Emergency department visits among individuals with six or seven and eight or more conditions were 1.53 [1.44–1.63] and 1.92 [1.80–2.05], respectively. Comorbid chronic kidney diseases were associated with the highest adjusted rate ratios of hospitalizations (1.81 [1.74–1.89]), whereas comorbid chronic ulcer of the skin was associated with the highest adjusted rate ratios of Accident and Emergency department visits (1.73 [1.61–1.85]). Healthcare utilization for individuals with dementia differed substantially by both the number of comorbid chronic conditions and the presence of some specific comorbid conditions. These findings further highlight the importance of taking account of multiple long-term conditions in tailoring the care approach and developing healthcare plans for people with dementia.
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- Zhang, Yingyang, et al.
(författare)
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Prescription Patterns of Antidementia and Psychotropic Drugs in People Living With Dementia : Findings From the Clinical Pathway Study of Alzheimer's Disease in China
- 2022
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 23:6, s. 1073-
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Evidence about prescribing patterns of dementia medication in China is lacking. This study aimed to examine prescribing rates of antidementia and psychotropic drugs and factors associated with drug prescription for dementia in China.Design: A multicenter observational study.Setting and Participants: This study employed cross-sectional data from the Clinical Pathway for Alzheimer's Disease in China study that was conducted in 28 memory clinics at tertiary hospitals across 14 provinces between 2012 and 2013. Patients aged ≥45 years with a diagnosis of dementia were included.Methods: Antidementia and psychotropic drugs were classified according to the Anatomical Therapeutic Chemical codes. Odds ratios (ORs) of putative factors associated with prescription patterns were estimated using logistic regressions.Results: A total of 751 respondents were included in this study, 77.8% of whom were prescribed antidementia drugs, and 33.0% were prescribed at least 1 psychotropic drug. The concomitant prescription rate of antidementia and psychotropic drugs was 24.1%. Frontotemporal dementia [OR 9.92 (99.17% CI 3.08-42.70)], severe dementia [4.25 (1.88-9.79)], and apathy [1.94 (1.18-3.20)] were significantly associated with an elevated likelihood of memantine prescription. Psychotic symptoms [1.84 (1.02-3.35)], agitation [1.91 (1.08-3.40)], and depressive symptoms [2.10 (1.12-3.94)] were significantly associated with the coprescription of antidementia and psychotropic agents.Conclusions and Implications: The prescribing rate of antidementia drugs in the study sample was higher, whereas the rate of coprescription of psychotropic and antidementia drugs was lower than reported in Western studies. Dementia prescription practice was generally consistent with clinical guidelines in memory clinics in China, whereas the prescription of antidementia and psychotropic medication mainly depended on patients’ clinical symptoms.
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