This study evaluates the prognostic significance of quantitative chimerism to monitor minimal residual disease and predict relapse in acute leukemia (AL) patients following allogeneic hematopoietic ...SCT (HSCT). The quantitative chimerism levels of 129 AL patients were measured using RQ-PCR based on 29 sequence polymorphisms. Receiver-operating characteristic curve indicated that the optimal cutoff point to predict an inevitable relapse was 1.0%, which results in 100.0% sensitivity and 79.6% specificity.The relapse rate of patients with chimerism >1.0% at 2 years was 55.0%, whereas that for patients with chimerism <1.0% was 0%(P=0.000). Quantitative chimerism >1.00% indicated a higher probability of relapse. Cox multivariate analysis indicated that quantitative chimerism >1.00% was associated with lower disease-free survival (hazard ratio (HR)=10.825; 95% confidence interval (CI) =4.704-24.912, P=0.000) and lower OS (HR=8.681; 95% CI=3.728-20.212, P=0.000). Patients (24/47 with quantitative chimerism >1.00%) who received preemptive modified DLI immunotherapy had significantly lower relapse rate (37.5%) than those (n=9) who did not (100%; P=0.001). Thus, quantitative chimerism is an independent prognostic factor that predicts clinical outcomes after HSCT and provides a guide for suitable interventions.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One ...possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children's Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests.
The interaction between dynamic recrystallization (DRX) and texture evolution of AZ80 magnesium alloy during hot deformation was investigated by EBSD analysis. A series of compression experiments ...along extrusion (ED) and radius (RD) direction were carried out on the as-extruded AZ80 magnesium alloy with <101‾0>//ED fiber texture at 200–300 °C. The results show that there are a more homogeneous microstructure and a stronger softening trend on the true stress-strain curves in ED than in RD. Texture in ED tends to rotate towards the //ED basal texture and its total intensity weakens, while the <101‾0>//ED and <112‾0>//ED fiber texture in RD present a sharpening phenomenon. The compression in ED activates discontinuous dynamic recrystallization (DDRX) mechanism and forms dynamically recrystallized grains with random orientation, which is beneficial to optimize the texture and improve the formability of AZ80 magnesium alloy. The deformation in RD activates the continuous dynamic recrystallization (CDRX) mechanism and produces dynamically recrystallized grains following the orientation of parent grains, which results in the sharpening of the initial texture and is unfavorable for weakening the anisotropy of AZ80 magnesium alloy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The process of metastasis is complex
. In breast cancer, there are frequently long time intervals between cells leaving the primary tumour and growth of overt metastases
. Reasons for disease ...indolence and subsequent transition back to aggressive growth include interactions with myeloid and fibroblastic cells in the tumour microenvironment and ongoing immune surveillance
. However, the signals that cause actively growing cells to enter an indolent state, thereby enabling them to survive for extended periods of time, are not well understood. Here we reveal how the behaviour of indolent breast cancer cells in the lung is determined by their interactions with alveolar epithelial cells, in particular alveolar type 1 cells. This promotes the formation of fibronectin fibrils by indolent cells that drive integrin-dependent pro-survival signals. Combined in vivo RNA sequencing and drop-out screening identified secreted frizzled-related protein 2 (SFRP2) as a key mediator of this interaction. Sfrp2 is induced in breast cancer cells by signals from lung epithelial cells and promotes fibronectin fibril formation and survival, whereas blockade of Sfrp2 expression reduces the burden of indolent disease.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. ...Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
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•Glioma spheroid cell lines are molecularly stable in vitro models over time.•Tumor spheroid cell lines allow for reproducible drug testing.•Gene expression profiles may predict in vitro drug response of glioma cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The interbasin long-distance water transfer project is key support for the reasonable allocation of water resources in a large-scale area, which can optimize the spatio-temporal change of water ...resources to secure the amount of water available. Large-scale water transfer projects have a deep influence on ecosystems; besides, global climate change causes uncertainty and additive effect of the environmental impact of water transfer projects. Therefore, how to assess the ecological and environmental impact of megaprojects in both construction and operation phases has triggered a lot of attention. The water-output area of the western route of China's South-North Water Transfer Project was taken as the study area of the present article. According to relevant evaluation principles and on the basis of background analysis, we identified the influencing factors and established the diagnostic index system. The climate-hydrology-ecology coupled simulation model was used to simulate and predict ecological and environmental responses of the water resource area in a changing environment. The emphasis of impact evaluation was placed on the reservoir construction and operation scheduling, representative river corridors and wetlands, natural reserves and the water environment below the dam sites. In the end, an overall evaluation of the comprehensive influence of the project was conducted. The research results were as follows: the environmental impacts of the western route project in the water resource area were concentrated on two aspects: the permanent destruction of vegetation during the phase of dam construction and river impoundment, and the significant influence on the hydrological situation of natural river corridor after the implementation of water extraction. The impact on local climate, vegetation ecology, typical wetlands, natural reserves and the water environment of river basins below the dam sites was small.
The strictest ever Clean Air Action has been implemented since 2013 at nationwide scale in China. Nevertheless, PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5 μm) mass and ...number of ultrafine particles (UFPs, the particles with diameters smaller than 100 nm) exhibited contrasting response to the emission mitigation policies. Unlike reduction of PM2.5 and number of accumulation mode particles, UFPs number decreased from 2012 to 2015, and then has begun to increase sharply since 2016, and annual change of number in nucleation mode particles can reach 40% at noontime during 2017–2019. We examined inter‐annual trends of mode diameter, frequency of new particle formation (NPF) events, formation and growth rates, and particles were found to be much finer and NPF events have been more frequent since 2017. The much higher temperature and stronger solar radiation induced by PM2.5 reduction could promote the formation of secondary aerosol particles at noon.
Plain Language Summary
Since 2013, China has implemented the strictest ever air pollution control policies, which resulted in substantial reductions in PM2.5 mass concentrations. However, it is still unclear how the recent stringent control measures influence number concentration of ultrafine particles, part of them from secondary formation. Furthermore, it remained a critical challenge to study the effect of PM2.5 reduction on formation of secondary pollutants. Using long‐term particle number size distribution (PNSD) data, we found a dramatic increasing trend in UFPs number after 2016 in urban Lanzhou of west China with maximum increase in nucleation mode particles at noon. Further, we checked the inter‐annual variations of mode diameter of PNSDs, NPF frequency, formation and growth rates, and then frequent new particle formation (NPF) events were found to dominate the variation in UFPs number during the observation period. The high temperature and strong solar radiation induced by PM2.5 reduction in response to emission mitigation policies could promote occurrence of NPF events, and thus resulted in increase in UFPs. This study is important for revising future emission control measures to reduce number concentrations of ultrafine particles.
Key Points
Annual change of N13–25 at noon time increased by 40% during 2017–2019
Increases in ultrafine particles were mainly induced by more frequent NPF events
NPF is increasingly frequent due to reduction in Coagulation sink in response to Clean Air Action in China
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from ...astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
CML treatment with tyrosine kinase inhibitors (TKIs) has improved many patients' prognosis, but during the disease's terminal phase, the blast crisis (CML-BC), has been disappointing. Allo-HSCT is ...another treatment, but survival rates are still disappointing. Currently, a combination of these two is suggested but with little evidence. This retrospective comparison reports on this combination and TKI alone for treatment of CML-BC. Of the 83 CML-BC patients, 45 received TKIs (imatinib; nilotinib or dasatinib after imatinib resistance; TKIs group) and 38 were treated with allo-HSCT after TKI (TKIs+allo-HSCT group). Treatment success was measured in terms of the hematologic, cytogenic and molecular responses, and subject outcome. Follow-up was 30-126 months or until death. Univariate and multivariate analyses determined EFS and OS predictors. Allo-HSCT significantly improved the 4-year OS (46.7 vs 9.7%, P<0.001) and EFS (47.1 vs 6.7%, P<0.001) compared to TKI treatment alone. Hemoglobin <100 g/L, non-return to chronic phase after TKI therapy and TKI treatment alone are independent adverse predictors of OS and EFS. Allo-HSCT with individualized intervention after TKI therapy is superior to TKI alone for CML-BC.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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