Initiating-clone analysis in patients with acute myeloid leukemia secondary to essential thrombocythemia.

Most of essential thrombocythemia (ET) patients have the clone harboring a mutation in one of the JAK2, CALR, or MPL gene, and these clones generally acquire additional mutations at transformation to acute myeloid leukemia (AML). However, the proliferation of triple-negative clones has sometimes been observed at AML transformation. To clarify the clonal evolution of ET to AML, we analyzed paired samples at ET and AML transformation in eight patients. We identified that JAK2-unmutated AML clones proliferated at AML transformation in three patients in whom the JAK2-mutated clone was dominant at ET. In two patients, TET2-mutated, but not JAK2-mutated, clones might be common initiating clones for ET and transformed AML. In a patient with JAK2-mutated ET, SMARCC2, UBR4, and ZNF143, but not JAK2, -mutated clones proliferated at AML transformation. Precise analysis using single-cell sorted CD34+/CD38- fractions suggested that ET clone with JAK2-mutated and AML clone with TP53 mutation was derived from the common clone with these mutations. Although further study is required to clarify the biological significance of SMARCC2, UBR4, and ZNF143 mutations during disease progression of ET and AML transformation, the present results demonstrate the possibility of a common initial clone involved in both ET and transformed AML.

Molecular templating of layered halide perovskite nanowires.

Layered metal-halide perovskites, or two-dimensional perovskites, can be synthesized in solution, and their optical and electronic properties can be tuned by changing their composition. We report a molecular templating method that restricted crystal growth along all crystallographic directions except for [110] and promoted one-dimensional growth. Our approach is widely applicable to synthesize a range of high-quality layered perovskite nanowires with large aspect ratios and tunable organic-inorganic chemical compositions. These nanowires form exceptionally well-defined and flexible cavities that exhibited a wide range of unusual optical properties beyond those of conventional perovskite nanowires. We observed anisotropic emission polarization, low-loss waveguiding (below 3 decibels per millimeter), and efficient low-threshold light amplification (below 20 microjoules per square centimeter).

Comparison of clonal architecture between primary and immunodeficient mouse-engrafted acute myeloid leukemia cells.

Patient-derived xenografts (PDX) are widely used as human cancer models. Previous studies demonstrated clonal discordance between PDX and primary cells. However, in acute myeloid leukemia (AML)-PDX models, the significance of the clonal dynamics occurring in PDX remains unclear. By evaluating changes in the variant allele frequencies (VAF) of somatic mutations in serial samples of paired primary AML and their PDX bone marrow cells, we identify the skewing engraftment of relapsed or refractory (R/R) AML clones in 57% of PDX models generated from multiclonal AML cells at diagnosis, even if R/R clones are minor at <5% of VAF in patients. The event-free survival rate of patients whose AML cells successfully engraft in PDX models is consistently lower than that of patients with engraftment failure. We herein demonstrate that primary AML cells including potentially chemotherapy-resistant clones dominantly engraft in AML-PDX models and they enrich pre-existing treatment-resistant subclones.

Movement Patterns and Diel Activity of Anguilla japonica in the Middle Part of a Large River in South Korea.

To investigate movement patterns and diel activities of Anguilla japonica in the freshwater ecosystem, we applied acoustic telemetry on A. japonica in the Geum River, a large river in South Korea. The acoustic tags were attached on 19 individuals of A. japonica (12 with a depth sensor) in May and October 2015 and tracked at approximately 100-km sections from an estuary barrage by 20 automatic listening stations. Only four individuals showed longitudinal movement (mean, 5.2 km), and others were detected by the receivers at release sites; therefore, A. japonica showed high site fidelity. We did not identify seaward migration during the study period (May to November). Conversely, A. japonica showed active diel movement. The number of detections (p = 0.002) and movement distance (p = 0.004) were higher at night-time (18:00-06:00). As most individuals were actively moving at nighttime, we confirmed that A. japonica is nocturnal, although few individuals also showed daytime movement. Although the population and habitats of A. japonica have been decreasing simultaneously, the East-Asian countries are still severely exploiting rivers and streams to use water resources, and result in habitat simplification generated. Therefore, these results contribute to effective A. japonica management regarding habitat and population conservation and restoration.

Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features.

BACKGROUND: Recently, various blood cell lineages expressing the BCR-ABL fusion gene in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have been reported. However, the biological and clinical significance of these BCR-ABL lineages has not been established; therefore, we aimed to clarify the impacts of these different BCR-ABL-expressing lineages. PATIENTS: Multi-lineage BCR-ABL expression (multi-Ph) was defined as BCR-ABL expression outside of the B-lineage compartment, as determined by fluorescence in situ hybridization (FISH) in peripheral blood neutrophils and bone marrow clots, and flow cytometry-sorted polymerase chain reaction (PCR). We analyzed IKZF1 deletion patterns by PCR, examined gene expression profiles using RNA sequencing, and compared treatment outcomes across different BCR-ABL-expressing lineages. RESULTS: Among the 21 multi-Ph patients in our 59-patient cohort (36%), BCR-ABL expression was detected at the multipotential progenitor level. However, no IKZF1 deletion patterns or gene expression profiles were identified that were specific for multi-Ph. However, multi-Ph patients were found to have better survival rates than patients with uni-lineage BCR-ABL expression [event-free survival (EFS): 74 vs. 33%, P = 0.01; overall survival (OS): 79 vs. 44% at 4 years, P = 0.01]. In multivariate analyses, multi-Ph was identified as a good prognostic factor for both EFS and OS. CONCLUSION: We confirmed that more than one-third of Ph+ALL patients could be classified as mutli-Ph. Although no specific molecular characteristics were identified for multi-Ph, this phenotype was associated with better treatment outcomes.

Thermostable Ion Gels for High-Temperature Operation of Electrolyte-Gated Transistors.

High-temperature durability is critical for application of organic materials in electronic devices that operate in harsh environments. In this work, thermostable physically cross-linked polymer electrolytes, or thermostable physical ion gels, were successfully developed using crystallization-induced phase separation of semicrystalline polyamides (PAs) in an ionic liquid (IL). In these ion gels, phase-separated PA crystals act as network junctions and enable the ion gels to maintain their mechanical integrity up to 180 °C. ILs and ion gels are suitable electrolyte candidates for thin-film devices operating at high temperatures because they outperform other electrolytes that use aqueous and organic solvents, owing to their superior thermal stability and nonvolatility. In addition to thermal stability, the PA gels exhibited high ionic conductivity (∼1 mS/cm) and specific capacitance (∼10 µF/cm2) at room temperature; these values increased significantly with increasing temperature, while the gel retained its solid-state mechanical integrity. These thermostable ion gels were successfully used as an electrolyte gate dielectric in organic thin-film transistors that operate at high temperatures (ca. 150 °C) and low voltages (<1 V). The transistors gated with the dielectrics had a high on/off current ratio of (3.04 ± 0.24) × 105 and a hole mobility of 2.83 ± 0.20 cm2/V·s. By contrast, conventional physical ion gels based on semicrystalline polymers of poly(vinylidene fluoride-co-hexafluoropropylene) and polyvinylidene fluoride lost their mechanical integrity and dewetted from a semiconductor channel at lower temperatures. Therefore, these results demonstrate an effective method of generating thermally stable, mechanically robust, and highly conductive solid polymer electrolytes for electronic and electrochemical devices operating in a wide temperature range.

Recyclable High-Performance Polymer Electrolyte Based on a Modified Methyl Cellulose-Lithium Trifluoromethanesulfonate Salt Composite for Sustainable Energy Systems.

Although energy-storage devices based on Li ions are considered as the most prominent candidates for immediate application in the near future, concerns with regard to their stability, safety, and environmental impact still remain. As a solution, the development of all-solid-state energy-storage devices with enhanced stability is proposed. A new eco-friendly polymer electrolyte has been synthesized by incorporating lithium trifluoromethanesulfonate into chemically modified methyl cellulose (LiTFS-LiSMC). The transparent and flexible electrolyte exhibits a good conductivity of near 1 mS cm-1 . An all-solid-state supercapacitor fabricated from 20 wt % LiTFS-LiSMC shows comparable specific capacitances to a standard liquid-electrolyte supercapacitor and an excellent stability even after 20 000 charge-discharge cycles. The electrolyte is also compatible with patterned carbon, which enables the simple fabrication of micro-supercapacitors. In addition, the LiTFS-LiSMC electrolyte can be recycled and reused more than 20 times with negligible change in its performance. Thus, it is a promising material for sustainable energy-storage devices.

Effects of modified constraint-induced movement therapy on upper extremity function and occupational performance of stroke patients.

[Purpose] The purpose of this research was to examine the effectiveness of modified constraint-induced movement therapy (mCIMT) on the upper extremity function and occupational performance of stroke patients. [Participants and Methods] An experimental study was carried out on two groups of 7 participants selected by a specific criterion. The experimental group received the mCIMT as well as the conventional rehabilitation therapy (CRT) for 5 days per week over a 2 week period. The control group received only the CRT. Outcome measures included the Manual Function Test (MFT), Motor Activity Log (MAL), and Canadian Occupational Performance Measure (COPM). [Results] Average amount of changes in the MAL and COPM is different in statistical analysis between the mCIMT and the CRT groups before and after the intervention. The mCIMT group showed significant improvements on MFT, MAL, and COPM before and after the intervention. [Conclusion] We suggest that the mCIMT improves the upper extremity function and occupational performance of stroke patients better than the CRT alone.