Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal myeloid malignancies. Though several recurrent mutations are closely correlated with clinical outcomes, data concerning the ...association between mutation variant allele frequencies (VAF) and prognosis are limited. In this study, we performed comprehensive VAF analyses of relevant myeloid‐malignancy related mutations in 698 MDS patients and correlated the results with their prognosis. Mutation VAF in DNMT3A, TET2, ASXL1, EZH2, SETBP1, BCOR, SFSF2, ZRSR2, and TP53 mutations correlated with outcomes. In multivariable analysis, DNMT3A and ZRSR2 mutations with high VAF and mutant IDH2, CBL, U2AF1, and TP53 were independent poor prognostic factors for overall survival. A substantial portion of patients in each revised International Prognostic Scoring System (IPSS‐R) risk group could be adjusted to different prognostic groups based on the integrated VAF and mutational profiles. Patients with these unfavorable mutations in each IPSS‐R risk subgroup had survivals worse than other patients of the same risk but similar to those in the next higher‐risk subgroup. Furthermore, patients harboring U2AF1 mutation might benefit from hypomethylating agents. This study demonstrated the critical role of VAF of mutations for risk stratification in MDS patients and may be incorporated in novel scoring systems.
DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In the present study of 500 ...patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate-risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease.
The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which ...myelodysplastic syndrome (MDS) with blasts of 10%–19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS‐SF3B1, and those with multi‐hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.7% of patients were reclassified to the MDS/AML group after the exclusion of 15 patients who were classified to the AML group. Patients with MDS/AML showed a distinct mutational landscape and had poorer outcomes, compared to those with MDS. In the MDS group, patients with MDS‐SF3B1 had higher frequencies of DNMT3A and TET2 mutations than those with MDS, not otherwise specified, with single lineage dysplasia or multilineage dysplasia. Patients with mutated TP53 were associated with dismal outcomes, irrespective of the blast percentage. In conclusion, this study showed that the ICC facilitates efficient segregation and risk‐stratification of MDS which can help guide the treatment choice of patients with the disease.
Case allocation of MDS patients defined by 2016 WHO classification and 2022 ICC.
In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we ...performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.
Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software.
Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008.
HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Acute myeloid leukemia (AML) with hyperleukocytosis (HL) is intuitively thought as a unique group with dismal prognosis. However, comprehensive studies regarding the genetic landscape and ...clinical outcome in this group of patients are limited.
Methods
A total of 693 newly diagnosed de novo non‐M3 AML patients were consecutively enrolled. We compared relevant mutations in 20 genes between AML patients with or without HL and exposed their prognostic implications.
Results
Hyperleukocytosis, defined as initial white blood cell counts above 50 000/μL, occurred in 28.9% of AML patients. HL patients had higher incidences of FLT3‐ITD, NPM1, DNMT3A, CEBPA, and TET2 mutations. Multivariate analysis demonstrated that HL was an independent poor prognostic factor for overall survival and disease‐free survival in total patients, those with intermediate‐risk cytogenetics and normal karyotype irrespective of genetic alterations. Intriguingly, HL predicted poor survival in CEBPA double mutated, NPM1 + /FLT3‐ITD‐ and NPM1‐/FLT3‐ITD‐ patients. Further, HL patients who received allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in first complete remission (CR) had a significantly longer overall survival and disease‐free survival than those without allo‐HSCT.
Conclusions
Hyperleukocytosis is an independent poor prognostic factor irrespective of cytogenetics and mutation status. Allo‐HSCT in first CR seems to ameliorate the poor prognostic impact of HL.
In this study we employed 1-chloronaphthalene (CN) and 1,8-diiodooctane (DIO) as binary additives exhibiting complementarily preferential solubility for processing the crystalline conjugated polymer ...polybis(dodecyl)thiophene-dodecyl-thieno3,4-
c
pyrrole-4,6-dione (PBTC
12
TPD) and the fullerene 6,6-phenyl-C
71
-butyric acid methyl ester (PC
71
BM) in chloroform. Using synchrotron grazing-incidence small-/wide-angle X-ray scattering and transmission electron microscopy to analyse the structure of the PBTC
12
TPD–PC
71
BM blend films, we found that the binary additives with different volume ratios in the processing solvent allow us to tune the relative population of face-on to edge-on PBTC
12
TPD lamellae and the size of PC
71
BM clusters in the blend films; the sizes of the fractal-like PC
71
BM clusters and the aggregated domains of PC
71
BM clusters increased and decreased, respectively, upon increasing the amount of DIO, whereas the relative ratio of face-on to edge-on PBTC
12
TPD lamellae increased upon increasing the amount of CN. When fabricating the photovoltaic devices, the short-circuit current density of the devices with the PBTC
12
TPD–PC
71
BM active layer having been processed with the binary additives is higher than that of the device incorporating an active layer processed without any additive. As a result, the power conversion efficiency of a device incorporating an active layer of PBTC
12
TPD–PC
71
BM (1 : 1.5, w/w) processed with binary additives of 0.5% DIO and 1% CN in chloroform increased to 6.8% from a value of 4.9%, a relative increase of 40%, for the corresponding device containing the same active layer but processed without any additive.
The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN‐2022. However, validation in a ...large real‐world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN‐2022 in a cohort of 809 de novo, non‐M3, younger (ages 18–65 years) AML patients receiving standard chemotherapy. The risk categories of 106 (13.1%) patients were reclassified from that determined using ELN‐2017 to that determined using ELN‐2022. The ELN‐2022 effectively helped distinguish patients as favorable, intermediate, and adverse risk groups in terms of remission rates and survival. Among patients who achieved first complete remission (CR1), allogeneic transplantation was beneficial for those in the intermediate risk group, but not for those in the favorable or adverse risk groups. We further refined the ELN‐2022 system by re‐categorizing AML patients with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 with KIThigh, JAK2 or FLT3‐ITDhigh mutations into the intermediate risk subset, AML patients with t(7;11)(p15;p15)/NUP98::HOXA9 and AML patients with co‐mutated DNMT3A and FLT3‐ITD into the adverse risk subsets, and AML patients with complex or monosomal karyotypes, inv (3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2,MECOM(EVI1) or TP53 mutation into the very adverse risk subset. The refined ELN‐2022 system performed effectively to distinguish patients as favorable, intermediate, adverse, and very adverse risk groups. In conclusion, the ELN‐2022 helped distinguish younger, intensively treated patients into three groups with distinct outcomes; the proposed refinement of ELN‐2022 may further improve risk stratification among AML patients. Prospective validation of the new predictive model is necessary.
This study provides new evidence on a long postulated mechanism of phase separation in a polymer/fullerene mixture during spin coating for controlled nanodomains of oriented crystallization and ...heterojunctions that favor applications in polymer solar cells (PSCs). The simultaneous nanoscale phase separation and crystallization during spin coating of the mixture are traced using in situ grazing‐incidence small‐ and wide‐angle X‐ray scattering. Combined with the complimentary results from time‐resolved optical reflectance spectroscopy, transient stratification of the liquid film during the transition from the flow‐ to evaporation‐dominated stage of spin coating is disclosed; the vertical liquid–liquid phase separation incubates a supersaturated skin layer where fullerene aggregation and polymer crystallization occur and develop concomitantly. Shortly after the transition, the near‐surface structural development is largely pinned, leaving the solvent‐rich bottom layer to diminish via solvent diffusion and evaporation through the thickened skin layer that finally condenses into the spin‐coated film upon solvent depletion. The shear‐enhanced surface layering and supersaturation for the surface‐down nanostructural development are unexpected in all the existing structural models for PSCs. The mechanistic understanding of coupled vertical phase separation and local nanosegregation provides new insights and alternative strategy to the morphology control of spin‐cast PSC active layers in particular and various solution‐processed polymeric films in general.
Surface layering and supersaturation over transition of the flow‐ to evaporation‐dominance of the spin coating of a polymer/fullerene mixture lead to surface‐down structural development of coupled vertical liquid–liquid phase separation and local nanosegregation/crystallization. A segregated upper layer enriched with nanostructures transforms into the final spin‐coated film, after solvent depletes from the bottom layer.
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•Dual plasmonic nanostructure with deposited Au nanodots and embedded Au nanoparticles.•Localized surface plasmon resonance.•The efficiency of the device incorporating the ...nanostructure is enhanced by 20%.
In this study, we investigated the effects of plasmonic resonances induced by gold nanodots (Au NDs), thermally deposited on the active layer, and octahedral gold nanoparticles (Au NPs), incorporated within the hole transport layer, on the performance of bulk heterojunction polymer solar cells (PSCs) based on poly(3-hexyl thiophene) (P3HT) and 6,6-phenyl-C61butyric acid methyl ester (PC61BM). Thermal deposition of 5.3-nm Au NDs between the active layer and the cathode in a P3HT:PC61BM device resulted in the power conversion efficiency (PCE) of 4.6%—that is 15% greater than that (4.0%) for the P3HT:PC61BM device without Au NDs. The Au NDs provided near-field enhancement through excitation of the localized surface plasmon resonance (LSPR), thereby enhancing the degree of light absorption.
In addition to the thermally deposited Au-NDs, embedding Au NPs within the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) to form a dual metallic nanostructure can further enhance PCE to 4.8%—that is about 20% greater than that of the conventional P3HT:PC61BM cell. Thus, Au NPs and Au NDs appear to have great potential for the application in high-efficiency LSPR-enhanced PSCs.
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