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- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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3. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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5. |
- Pantazis, N, et al.
(författare)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Tidskriftsartikel (refereegranskat)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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8. |
- Dans, Madeline G., et al.
(författare)
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Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
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9. |
- Barekat, A., et al.
(författare)
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Generation of mean flows in rotating anisotropic turbulence : The case of solar near-surface shear layer
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
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Tidskriftsartikel (refereegranskat)abstract
- Context. Results from helioseismology indicate that the radial gradient of the rotation rate in the near-surface shear layer (NSSL) of the Sun is independent of latitude and radius. Theoretical models using the mean-field approach have been successful in explaining this property of the NSSL, while global direct or large-eddy magnetoconvection models have so far been unable to reproduce this. Aims. We investigate the reason for this discrepancy by measuring the mean flows, Reynolds stress, and turbulent transport coefficients under conditions mimicking those in the solar NSSL. Methods. Simulations with as few ingredients as possible to generate mean flows were studied. These ingredients are inhomogeneity due to boundaries, anisotropic turbulence, and rotation. The parameters of the simulations were chosen such that they matched the weakly rotationally constrained NSSL. The simulations probe locally Cartesian patches of the star at a given depth and latitude. The depth of the patch was varied by changing the rotation rate such that the resulting Coriolis numbers covered the same range as in the NSSL. We measured the turbulent transport coefficient relevant for the nondiffusive (?-effect) and diffusive (turbulent viscosity) parts of the Reynolds stress and compared them with predictions of current mean-field theories. Results. A negative radial gradient of the mean flow is generated only at the equator where meridional flows are absent. At other latitudes, the meridional flow is comparable to the mean flow corresponding to differential rotation. We also find that the meridional components of the Reynolds stress cannot be ignored. Additionally, we find that the turbulent viscosity is quenched by rotation by about 50% from the surface to the bottom of the NSSL. Conclusions. Our local simulations do not validate the explanation for the generation of the NSSL from mean-field theory where meridional flows and stresses are neglected. However, the rotational dependence of the turbulent viscosity in our simulations agrees well with theoretical predictions. Moreover, our results agree qualitatively with global convection simulations in that an NSSL can only be obtained near the equator.
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10. |
- Berbakov, Maria E, et al.
(författare)
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Adapting a community pharmacy intervention to improve medication safety.
- 2024
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Ingår i: Journal of the American Pharmacists Association : JAPhA. - 1544-3450. ; 64:1, s. 159-168
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Community pharmacies are an ideal location to address challenges of over-the-counter medication safety, yet many successful interventions are only tested in a few pharmacies without expansion, creating unrealized opportunities to improve patient care on a larger scale. Scaling up to numerous pharmacies can be challenging because each community pharmacy has unique needs and layouts and requires individualized adaptation.OBJECTIVES: This paper reports techniques for (a) adapting a community pharmacy intervention to fit the unique physical layout and patient needs of health system pharmacy sites without increasing staff workload, (b) identifying strategies to gather feedback on adaptations from stakeholders, and (c) developing materials to share with pharmacy champions for them to independently implement and sustain the intervention in their organization.PRACTICE DESCRIPTION: The study team collaborated with Aurora Pharmacy, Inc to develop an intervention designed to increase awareness of safe over-the-counter medication use for older adults.PRACTICE INNOVATION: Senior Safe, a community pharmacy-based intervention, was designed, implemented, and tested using the Exploration, Preparation, Implementation, and Sustainment implementation framework.EVALUATION METHODS: Senior Safe was adapted through pilot testing and a randomized control trial. Feedback was collected from key stakeholders, including pharmacy staff, older adults, and a research advisory group.RESULTS: A finalized version of Senior Safe, as well as an implementation package, was provided to Aurora Pharmacy to integrate into all 63 sites.CONCLUSION: This multiphase study illustrated that refining an intervention is possible and welcomed by pharmacy staff, but it requires time, resources, and funds to create an impactful, sustainable community pharmacy intervention.
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12. |
- D'Angiolo, M., et al.
(författare)
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A yeast living ancestor reveals the origin of genomic introgressions
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- A yeast clonal descendant of an ancient hybridization event is identified and sheds light on the early evolution of the Saccharomyces cerevisiae Alpechin lineage and its abundant Saccharomyces paradoxus introgressions. Genome introgressions drive evolution across the animal(1), plant(2) and fungal(3) kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast(4), has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces cerevisiae Alpechin lineage(5), which carries abundant Saccharomyces paradoxus introgressions. We show that this clonal descendant, hereafter defined as a 'living ancestor', retained the ancestral genome structure of the first-generation hybrid with contiguous S. cerevisiae and S. paradoxus subgenomes. The ancestral first-generation hybrid underwent catastrophic genomic instability through more than a hundred mitotic recombination events, mainly manifesting as homozygous genome blocks generated by loss of heterozygosity. These homozygous sequence blocks rescue hybrid fertility by restoring meiotic recombination and are the direct origins of the introgressions present in the Alpechin lineage. We suggest a plausible route for introgression evolution through the reconstruction of extinct stages and propose that genome instability allows hybrids to overcome reproductive isolation and enables introgressions to emerge.
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14. |
- Gilson, Nicholas D, et al.
(författare)
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High intensity and sprint interval training, and work-related cognitive function in adults : A systematic review.
- 2023
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 33:6, s. 814-833
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess evidence on the impact of acute and chronic high intensity interval training (HIIT) and sprint interval training (SIT) on work-related performance tests of cognitive function in adults.METHODS: The databases PubMed, CINAHL, Scopus, PsycINFO, Embase and the Cochrane Library were searched for relevant articles up to August 2022. Eligible studies assessed the effects of HIIT (70-100% VO2max ) and/or SIT (≥100% VO2max ) on cognitive function test scores in cognitively healthy adults, relative to a control or comparative exercise group/condition. Data on participant characteristics, exercise protocol, key outcomes and intervention setting were extracted. Study quality was assessed using a 9 (single session HIIT/SIT) and 14 (multiple session HIIT/SIT) item checklist.RESULTS: 36 studies (15 countries; n=11 to 945 participants) met inclusion criteria. Mean quality scores were 'fair-to-good' for acute (single session; mean=6.9 [SD 1.0]), and chronic (multiple session; mean=9.8 [SD 1.6]) training studies. Eighteen from 36 studies (12/20 [55%] acute and 6/16 [38%] chronic training studies) evidenced significant improvements in aspects of cognitive function related to work performance (i.e., attention, inhibition, memory, information processing speed, cognitive flexibility, intelligence, reaction time and learning). Only four studies tested the impact of HIIT/SIT on cognitive function in a work-based setting (e.g., the office or home).CONCLUSIONS: While there is promising evidence, particularly from acute training studies, to indicate that high intensity, short duration exercise benefits cognitive function in adults, there is very limited evidence of application in workplace contexts. To better understand the potential benefits to employee performance and safety, HIIT/SIT and cognitive function research needs to transition from laboratory to 'in-situ' occupational settings.
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16. |
- McCallum, Fiona J., et al.
(författare)
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Differing rates of antibody acquisition to merozoite antigens in malaria : Implications for immunity and surveillance
- 2017
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Ingår i: Journal of Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 101:4, s. 913-925
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance.
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17. |
- Saint-Leger, A., et al.
(författare)
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The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres
- 2014
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Ingår i: Cell Cycle. - : Taylor andamp; Francis: STM, Behavioural Science and Public Health Titles. - 1538-4101 .- 1551-4005. ; 13:15, s. 2469-2479
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Tidskriftsartikel (refereegranskat)abstract
- The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication. © 2014 Landes Bioscience.
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18. |
- Uzochukwu, Benjamin, et al.
(författare)
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Health policy and systems research and analysis in Nigeria : examining health policymakers' and researchers' capacity assets, needs and perspectives in south-east Nigeria.
- 2016
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Ingår i: Health Research Policy and Systems. - : BioMed Central. - 1478-4505. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Health policy and systems research and analysis (HPSR+A) has been noted as central to health systems strengthening, yet the capacity for HPSR+A is limited in low- and middle-income countries. Building the capacity of African institutions, rather than relying on training provided in northern countries, is a more sustainable way of building the field in the continent. Recognising that there is insufficient information on African capacity to produce and use HPSR+A to inform interventions in capacity development, the Consortium for Health Policy and Systems Analysis in Africa (2011-2015) conducted a study with the aim to assess the capacity needs of its African partner institutions, including Nigeria, for HPSR+A. This paper provides new knowledge on health policy and systems research assets and needs of different stakeholders, and their perspectives on HPSR+A in Nigeria.METHODS: This was a cross-sectional study conducted in the Enugu state, south-east Nigeria. It involved reviews and content analysis of relevant documents and interviews with organizations' academic staff, policymakers and HPSR+A practitioners. The College of Medicine, University of Nigeria, Enugu campus (COMUNEC), was used as the case study and the HPSR+A capacity needs were assessed at the individual, unit and organizational levels. The HPSR+A capacity needs of the policy and research networks were also assessed.RESULTS: For academicians, lack of awareness of the HPSR+A field and funding were identified as barriers to strengthening HPSR+A in Nigeria. Policymakers were not aware of the availability of research findings that could inform the policies they make nor where they could find them; they also appeared unwilling to go through the rigors of reading extensive research reports.CONCLUSION: There is a growing interest in HPSR+A as well as a demand for its teaching and, indeed, opportunities for building the field through research and teaching abound. However, there is a need to incorporate HPSR+A teaching and research at an early stage in student training. The need for capacity building for HPSR+A and teaching includes capacity building for human resources, provision and availability of academic materials and skills development on HPSR+A as well as for teaching. Suggested development concerns course accreditation, development of short courses, development and inclusion of HPSR+A teaching and research-specific training modules in school curricula for young researchers, training of young researchers and improving competence of existing researchers. Finally, we could leverage on existing administrative and financial governance mechanisms when establishing HPSR+A field building initiatives, including staff and organizational capacity developments and course development in HPSR+A.
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19. |
- Uzochukwu, Benjamin, et al.
(författare)
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The challenge of bridging the gap between researchers and policy makers : experiences of a Health Policy Research Group in engaging policy makers to support evidence informed policy making in Nigeria
- 2016
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Ingår i: Globalization and Health. - : Springer Science and Business Media LLC. - 1744-8603. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Getting research into policy and practice (GRIPP) is a process of going from research evidence to decisions and action. To integrate research findings into the policy making process and to communicate research findings to policymakers is a key challenge world-wide. This paper reports the experiences of a research group in a Nigerian university when seeking to 'do' GRIPP, and the important features and challenges of this process within the African context.METHODS: In-depth interviews were conducted with nine purposively selected policy makers in various organizations and six researchers from the universities and research institute in a Nigerian who had been involved in 15 selected joint studies/projects with Health Policy Research Group (HPRG). The interviews explored their understanding and experience of the methods and processes used by the HPRG to generate research questions and research results; their involvement in the process and whether the methods were perceived as effective in relation to influencing policy and practice and factors that influenced the uptake of research results.RESULTS: The results are represented in a model with the four GRIPP strategies found: i) stakeholders' request for evidence to support the use of certain strategies or to scale up health interventions; ii) policymakers and stakeholders seeking evidence from researchers; iii) involving stakeholders in designing research objectives and throughout the research process; and iv) facilitating policy maker-researcher engagement in finding best ways of using research findings to influence policy and practice and to actively disseminate research findings to relevant stakeholders and policymakers. The challenges to research utilization in health policy found were to address the capacity of policy makers to demand and to uptake research, the communication gap between researchers, donors and policymakers, the management of the political process of GRIPP, the lack of willingness of some policy makers to use research, the limited research funding and the resistance to change.CONCLUSIONS: Country based Health Policy and Systems Research groups can influence domestic policy makers if appropriate strategies are employed. The model presented gives some direction to potential strategies for getting research into policy and practice in the health care sector in Nigeria and elsewhere.
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21. |
- Zhu, RJ, et al.
(författare)
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Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms
- 2021
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Ingår i: Cell research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 3231:112, s. 1244-1262
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Tidskriftsartikel (refereegranskat)abstract
- The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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