A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its ...stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.
This study determines the relative survival (RS) of Bacillus subtilis spores loaded on an N95 filtering facepiece respirator (FFR) after decontamination by five methods under worst‐case conditions. ...Relative survival was obtained by testing after decontamination and after storing the FFRs at 37°C and 95% relative humidity for 24 hours. The decontamination methods involved ethanol, bleach, ultraviolet irradiation (UVA 365 nm, UVC 254 nm), an autoclave, and a traditional electric rice cooker (TERC) that was made in Taiwan. Without decontamination, 59 ± 8% of the loaded spores survived for 24 hours. When 70% ethanol was added to the N95 FFR at a packing density of 0.23, the RS was 73 ± 5% initially and decayed to 22 ± 8% in 24 hours. Relative survival remained above 20% after 20 minutes of UVA irradiation. The other four decontamination measures achieved 99%‐100% biocidal efficacy, as measured immediately after the methods were applied to the test FFRs. Relative survival is a useful parameter for measuring sterilization or degree of disinfection. Bleach, UVC, an autoclave, and a TERC provide better biocidal efficacy than ethanol and UVA. Not only a higher filter quality but also a lower value of RS produced the most decontaminated FFR.
The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this ...study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
In this study, we investigate detailed electron dynamics in strong guide‐field reconnection (the normalized guide field is ∼1.5). This reconnection event is observed by the Magnetospheric Multiscale ...(MMS) spacecraft at the center of a flux rope in the magnetotail. With the presence of a large parallel electric field (E‖) in the electron current sheet, electrons are accelerated when streaming into this E‖ region from one direction, and decelerated from the other direction. Some decelerated electrons can reduce the parallel speed to ∼0 to form relatively isotropic electron distributions at one side of the electron current sheet, as the estimated acceleration potential satisfies the relation eΦ‖ ≥ kTe,‖, where Te,‖ is the electron temperature parallel to the magnetic field. Therefore, a large E‖ is generated to balance the parallel electron pressure gradient across the electron current sheet, since electrons at the other side of the current sheet are still anisotropic. Based on these observations, we further show that the electron beta is an important parameter in guide‐field reconnection, providing a new perspective to solve the large parallel electric field puzzle in guide‐field reconnection.
Plain Language Summary
Magnetic reconnection is a universal process that rapidly converts energy from the magnetic field to plasma. The energy conversion at kinetic scales is of particular interest to researchers, as it is directly related to reconnection process in the central diffusion region. In general, the reconnecting magnetic fields do not have to be antiparallel, and an additional magnetic component known as the guide field (Bg) can appear in the direction perpendicular to the reconnecting plane. Recently, observations from Magnetospheric Multiscale (MMS) mission show a large electric field parallel to the local magnetic field, which is several times larger than the reconnection electric field, can appear in guide‐field reconnection, and impact electrons significantly. However, the generation of this large parallel electric field in strong guide‐field reconnection is still not fully understood. In this study, we suggest that the electron beta (ratio of the electron thermal pressure to the magnetic pressure) is an important parameter in guide‐field reconnection. Only within some proper electron beta range, a parallel pressure gradient across the electron current sheet can form to balance the large parallel electric field.
Key Points
We present detailed electron dynamics in guide‐field reconnection at the center of a flux rope
With eΦ‖ ≥ kTe,‖, the observed electron behaviors can be well explained
We suggest that electron beta is an important parameter for the generation of a large parallel electric field in guide‐field reconnection
The current status of research on boron nitride nanotubes (BNNTs)—carbon nanotube structural analogues—is discussed. Latest achievements in BNNT synthesis, morphology, and atomic structure analysis ...as well as physical, chemical, and functional property evaluations are reviewed. Similarities and differences between structural parameters and properties of BNNTs in comparison with conventional carbon nanotubes are particularly highlighted. Recent breakthroughs in BNNT filling, doping and functionalization, morphology, and electronic structure engineering are examined. Finally, prospective BNNT applications for fabricating field‐effect transistors, gas accumulators, and reinforcing polymer films are presented.
Boron nitride nanotubes (BNNTs) are well‐known structural analogues of carbon nanotubes (CNTs). This Review discusses the latest achievements in BNNT synthesis, morphology, and analysis, as well as their property evaluations. Similarities and differences between BNNTs and CNTs in particular are highlighted. Prospective BNNT applications for reinforcing polymer films, fabricating field‐effect transistors, and gas accumulators are presented.
PDF
