| 1. |
- Alsafadi, Hani N, et al.
(författare)
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Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery
- 2020
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 62:6, s. 681-691
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Forskningsöversikt (refereegranskat)abstract
- Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targets and therapies are needed. Precision-cut lung slices (PCLS) from healthy and diseased human tissue represent one promising tool that can closely recapitulate the complexity of the lung's native environment, and recently, improved methodologies and accessibility to human tissue have led to an increased use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to advance our understanding of CLD development, as well as drug discovery and validation for CLDs. PCLS enable investigators to study complex interactions among different cell types and the extracellular matrix in the native three-dimensional architecture of the lung. PCLS further allow for high-resolution (live) imaging of cellular functions in several dimensions. Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or transplantation, thus allowing the study of CLDs in living human tissue. Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic the onset and progression of CLDs, complementing studies in end-stage diseased tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the gap between target identification and translation into clinical studies, and thus open novel avenues for future precision medicine approaches.
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| 4. |
- Carlson, Benny, et al.
(författare)
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Så skapas en etnisk underklass
- 1997
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 5. |
- Cristancho, Edgar, et al.
(författare)
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Arterial oxygen saturation and hemoglobin mass in postmenopausal untrained and trained altitude residents.
- 2007
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Ingår i: High altitude medicine & biology. - : Mary Ann Liebert Inc. - 1527-0297 .- 1557-8682. ; 8:4, s. 296-306
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Tidskriftsartikel (refereegranskat)abstract
- Because of lacking ventilatory stimulation by sex hormones in postmenopausal women (PW), one might expect a lowered arterial oxygen saturation (S(O(2))) in hypoxia and therefore a stronger erythropoietic reaction than in young women (YW). Nine untrained (UTRPW) and 11 trained (TRPW) postmenopausal altitude residents (2600 m) were compared to 16 untrained (UTRYW) and 16 trained young women (TRYW) to check this hypothesis and to study the combined response to hypoxia and training. S(O(2)) was decreased in PW (89.2% +/- 2.2 vs. 93.6 +/- 0.7% in YW, p < 0.01). Hb mass, however, was similar in UT (UTRYW: 9.2 +/- 0.9 g/kg(1), UTRPW: 8.7 +/- 1.0 g/kg). But if body fat rise with age was excluded by relation to fat-free mass, Hb mass was increased in UTRPW (+1.2 g/kg, p < 0.05) compared to UTRYW. Training caused a similar rise of Hb mass in PW and YW (0.3 g/kg per mL/kg x min(1) rise in V(O(2peak))). There was no difference in erythropoietin among the groups. Ferritin was higher in PW than YW. The results show that female hormones and fitness level have to be considered in studies on erythropoiesis at altitude. The role of erythropoietin during chronic hypoxia still has to be clarified.
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| 7. |
- Osorio Galindo, Mauricio J., et al.
(författare)
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E-Friend : A Logical-Based AI Agent System Chat-Bot for Emotional Well-Being and Mental Health
- 2021
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Ingår i: Deceptive AI. - Cham : Springer. - 9783030917784 - 9783030917791 ; , s. 87-104
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Konferensbidrag (refereegranskat)abstract
- In this work, it is proposed the design of a Reasoning Logical Based Intelligent Agent System Chat-bot for Dialogue Composition (DC) named E-friend, which uses Logic Programming (LP) for reasoning tasks. The main contribution is the use of Knowledge Representation Reasoning with LP theories modelling the knowledge of the user agent (beliefs, intentions, and expectations) to reason, plan and to optimally solve the DC problem. Another contribution is the design of a system component that extends the theory of mind, for the user model, with emotions to detect if the user decepts to the system or to itself. This component has the aim to alert and inform the facilitator when E-friend detects possible deceit signals from the student. E-friend was designed to help first year university students to manage stress/anxiety to optimal well-being development and attempt the prevention of depression and addictions leading. Students can interact through a chat-bot (text-based questions and answers) to help the system learns from the user, at the same time the user learns from itself improving mental health well-being.
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| 8. |
- Sikkema, Lisa, et al.
(författare)
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An integrated cell atlas of the lung in health and disease
- 2023
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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| 9. |
- Vasamsetti, Sathish Babu, et al.
(författare)
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Apoptosis of hematopoietic progenitor-derived adipose tissue-resident macrophages contributes to insulin resistance after myocardial infarction
- 2020
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:553
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Tidskriftsartikel (refereegranskat)abstract
- Patients with insulin resistance have high risk of cardiovascular disease such as myocardial infarction (MI). However, it is not known whether MI can initiate or aggravate insulin resistance. We observed that patients with ST-elevation MI and mice with MI had de novo hyperglycemia and features of insulin resistance, respectively. In mouse models of both myocardial and skeletal muscle injury, we observed that the number of visceral adipose tissue (VAT)-resident macrophages decreased because of apoptosis after these distant organ injuries. Patients displayed a similar decrease in VAT-resident macrophage numbers and developed systemic insulin resistance after ST-elevation MI. Loss of VAT-resident macrophages after MI injury led to systemic insulin resistance in non-diabetic mice. Danger signaling-associated protein high mobility group box 1 was released by the dead myocardium after MI in rodents and triggered macrophage apoptosis via Toll-like receptor 4. The VAT-resident macrophage population in the steady state in mice was transcriptomically distinct from macrophages in the brain, skin, kidney, bone marrow, lungs, and liver and was derived from hematopoietic progenitor cells just after birth. Mechanistically, VAT-resident macrophage apoptosis and de novo insulin resistance in mouse models of MI were linked to diminished concentrations of macrophage colony-stimulating factor and adiponectin. Collectively, these findings demonstrate a previously unappreciated role of adipose tissue-resident macrophages in sensing remote organ injury and promoting MI pathogenesis.
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