Adverse prognostic impact of KIT exon 17 mutations despite negative flow cytometric measurable residual disease in pediatric acute myeloid leukemia with RUNX1::RUNX1T1.

Not available.

Azacitidine treatment for myeloid leukemia associated with Down syndrome: A nationwide retrospective study in Japan.

Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.

A case of gallbladder abscess caused by torsion that completely disappeared following drainage.

A woman in her 90s presented with loss of appetite, lower back pain, abdominal pain, and fever. Physical examination and subsequent blood tests indicated an inflammatory process, and computed tomography (CT) scans revealed gallbladder torsion with necrosis and abscess formation. The case involved successful management of this rare condition through percutaneous drainage without the need for surgical intervention, avoiding complications during follow-up. Remarkably, post-treatment CT showed complete resolution of the gallbladder abscess and the gallbladder itself was no longer visible. This case highlights the effectiveness of minimally invasive treatment for gallbladder torsion in elderly patients and underscores the potential for non-surgical intervention in managing complex abdominal conditions.

A case of inherited glycosylphosphatidylinositol deficiency caused by PGAP3 variant with uniparental isodisomy on chromosome 17.

BACKGROUND: Inherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17. METHOD: Clinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. RESULTS: The patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency. CONCLUSION: This is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.

Machine/deep learning-assisted hemoglobin level prediction using palpebral conjunctival images.

Palpebral conjunctival hue alteration is used in non-invasive screening for anaemia, whereas it is a qualitative measure. This study constructed machine/deep learning models for predicting haemoglobin values using 150 palpebral conjunctival images taken by a smartphone. The median haemoglobin value was 13.1 g/dL, including 10 patients with <11 g/dL. A segmentation model using U-net was successfully constructed. The segmented images were subjected to non-convolutional neural network (CNN)-based and CNN-based regression models for predicting haemoglobin values. The correlation coefficients between the actual and predicted haemoglobin values were 0.38 and 0.44 in the non-CNN-based and CNN-based models, respectively. The sensitivity and specificity for anaemia detection were 13% and 98% for the non-CNN-based model and 20% and 99% for the CNN-based model. The performance of the CNN-based model did not improve with a mask layer guiding the model's attention towards the conjunctival regions, however, slightly improved with correction by the aspect ratio and exposure time of input images. The gradient-weighted class activation mapping heatmap indicated that the lower half area of the conjunctiva was crucial for haemoglobin value prediction. In conclusion, the CNN-based model had better results than the non-CNN-based model. The prediction accuracy would improve by using more input data with anaemia.

Inhibition of the galactosyltransferase C1GALT1 reduces osteosarcoma cell proliferation by interfering with ERK signaling and cell cycle progression.

Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers and therapeutic targets, so we screened for DEGs in osteosarcoma. We found that osteosarcoma cases could be divided into fair and poor survival groups based on gene expression profiles. Among the genes upregulated in the poor survival group, siRNA-mediated knockdown of the glycosylation-related gene C1GALT1 suppressed osteosarcoma cell proliferation in culture. Gene expression, phosphorylation, and glycome array analyses also demonstrated that C1GALT1 is required to maintain ERK signaling and cell cycle progression. Moreover, the C1GALT1 inhibitor itraconazole suppressed osteosarcoma cell proliferation in culture, while doxycycline-induced shRNA-mediated knockdown reduced xenograft osteosarcoma growth in mice. Elevated C1GALT1 expression is a potential early predictor of poor prognosis, while pharmacological inhibition may be a feasible treatment strategy for osteosarcoma.

High IL2RA/CD25 expression is a prognostic stem cell biomarker for pediatric acute myeloid leukemia without a core-binding factor.

CD25 is an aberrant marker expressed on the leukemic stem cell (LSC) surface and an immunotherapy target in acute myeloid leukemia (AML). However, the clinical prevalence and significance of CD25 expression in pediatric AML are unknown. High IL2RA/CD25 expression in pediatric AML showed a stem cell-like phenotype, and elevated CD25 expression was associated with lower overall survival (p < .001) and event-free survival (p < .001) in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. This finding was reproduced in AML without a core-binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.

Simple algorithm for judging equivalence of differential-algebraic equation systems.

Mathematical formulas play a prominent role in science, technology, engineering, and mathematics (STEM) documents; understanding STEM documents usually requires knowing the difference between equation groups containing multiple equations. When two equation groups can be transformed into the same form, we call the equation groups equivalent. Existing tools cannot judge the equivalence of two equation groups; thus, we develop an algorithm to judge such an equivalence using a computer algebra system. The proposed algorithm first eliminates variables appearing only in either equation group. It then checks the equivalence of the equations one by one: the equations with identical algebraic solutions for the same variable are judged equivalent. If each equation in one equation group is equivalent to an equation in the other, the equation groups are judged equivalent; otherwise, non-equivalent. We generated 50 pairs of equation groups for evaluation. The proposed method accurately judged the equivalence of all pairs. This method is expected to facilitate comprehension of a large amount of mathematical information in STEM documents. Furthermore, this is a necessary step for machines to understand equations, including process models.

Organellar Glue: A Molecular Tool to Artificially Control Chloroplast-Chloroplast Interactions.

Organelles can physically interact to facilitate various cellular processes such as metabolite exchange. Artificially regulating these interactions represents a promising approach for synthetic biology. Here, we artificially controlled chloroplast-chloroplast interactions in living plant cells with our organelle glue (ORGL) technique, which is based on reconstitution of a split fluorescent protein. We simultaneously targeted N-terminal and C-terminal fragments of a fluorescent protein to the chloroplast outer envelope membrane or cytosol, respectively, which induced chloroplast-chloroplast interactions. The cytosolic C-terminal fragment likely functions as a bridge between two N-terminal fragments, thereby bringing the chloroplasts in close proximity to interact. We modulated the frequency of chloroplast-chloroplast interactions by altering the ratio of N- and C-terminal fragments. We conclude that the ORGL technique can successfully control chloroplast-chloroplast interactions in plants, providing a proof of concept for the artificial regulation of organelle interactions in living cells.

The photo-thermochemical properties and functions of Marchantia phototropin encoded by an unduplicated gene in land plant evolution.

Phototropin (phot) is a blue light photoreceptor in plants and possesses two photosensory light­oxygen-voltage (LOV1 and LOV2) domains with different photo-thermochemical properties. While liverworts contain a single copy of PHOT (e.g., MpPHOT in Marchantia polymorpha), many land plant species contain multicopy PHOT genes (e.g., AtPHOT1 and 2 in Arabidopsis thaliana) due to evolutionary gene duplication. The LOV domains of duplicated phot proteins have been studied in detail, but those of single-copy phot proteins remain to be characterized. As phot has not been duplicated in liverworts, we hypothesized that Mpphot may retain the ancestral function and photo-thermochemical properties. To learn more about the unduplicated phot proteins, we analyzed chloroplast relocation movement and the photo-thermochemical properties of LOV1 and LOV2 in Mpphot (Mpphot-LOV1 and Mpphot-LOV2, respectively). The function of Mpphot-LOV1, which induced a response to move chloroplasts to weak light (the accumulation response) in the absence of photoactive LOV2, differed from that of LOV1 of the duplicated phot proteins of A. thaliana (e.g., Atphot1-LOV1 preventing the accumulation response). On the other hand, the function of Mpphot-LOV2 was similar to that of LOV2 of the duplicated phots. The photo-thermochemical properties of Mpphot were a hybrid of those of the duplicated phots; the photochemical and thermochemical reactions of Mpphot were similar to those of the phot2- and phot1-type proteins, respectively. Our findings reveal conservation and diversification among LOV domains during phot duplication events in land plant evolution.

Temporal Evolution of the Gravitaxis of Euglena gracilis from a Single Cell.

Gravitaxis is one of the most important issues in the growth of microalgae in the water column; it determines how easily cells receive sunlight with a comfortable intensity that is below the damaging threshold. We quantitatively investigated and analyzed the gravitaxis and cell multiplication of Euglena gracilis using vertically placed microchambers containing a single cell. A temporal change in gravitaxis and cell multiplication was observed after transferring the cells to fresh culture medium for 9 days. We performed 29 individual experiments with 2.5 mm × 2.5 mm × 0.1 mm square microchambers and found that the cells showed positive, negative, and moderate gravitaxis in 8, 7, and 14 cases, respectively, after transferring to fresh culture medium. A common trend was observed for the temporal change in gravitaxis for the eight initially positive gravitaxis cases. The cells with initially positive gravitaxis showed a higher rate of cell multiplication than those with initially negative gravitaxis. We also discussed the gravitaxis mechanism of E. gracilis from the observed trend of gravitaxis change and swimming traces. In addition, bioconvection in a larger and thicker chamber was investigated at a millimeter scale and visualized.

The Cell Division Cycle of Euglena gracilis Indicates That the Level of Circadian Plasticity to the External Light Regime Changes in Prolonged-Stationary Cultures.

In unicellular photosynthetic organisms, circadian rhythm is tightly linked to gating of cell cycle progression, and is entrained by light signal. As several organisms obtain a fitness advantage when the external light/dark cycle matches their endogenous period, and aging alters circadian rhythms, senescence phenotypes of the microalga Euglena gracilis of different culture ages were characterized with respect to the cell division cycle. We report here the effects of prolonged-stationary-phase conditions on the cell division cycles of E. gracilis under non-24-h light/dark cycles (T-cycles). Under T-cycles, cells established from 1-month-old and 2-month-old cultures produced lower cell concentrations after cultivation in the fresh medium than cells from 1-week-old culture. This decrease was not due to higher concentrations of dead cells in the populations, suggesting that cells of different culture ages differ in their capacity for cell division. Cells from 1-week-old cultures had a shorter circadian period of their cell division cycle under shortened T-cycles than aged cells. When algae were transferred to free-running conditions after entrainment to shortened T-cycles, the young cells showed the peak growth rate at a time corresponding to the first subjective night, but the aged cells did not. This suggests that circadian rhythms are more plastic in younger E. gracilis cells.

Cobalt-Catalyzed Hartung-Mukaiyama Cyclization of γ-Hydroxy Olefins: Stereocontrolled Synthesis of the Tetrahydrofuran Moiety of Amphidinolide N.

Cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins is known as an atom- and step-economical means for stereoselective synthesis of 2,5-trans-substituted tetrahydrofuran derivatives. In this study, we investigated the synthesis of a series of 2,5-substituted tetrahydrofuran derivatives by means of a cobalt-catalyzed Hartung-Mukaiyama cyclization. The stereochemical consequence of the reaction was found to be largely dependent on the substitution pattern and relative configuration of γ-hydroxy olefins. 2,5-cis-Substituted tetrahydrofuran derivatives could be obtained diastereoselectively from appropriately substituted γ-hydroxy olefins. Additionally, relatively bulky olefin substituents and unprotected hydroxy groups at non-interfering positions (e.g., α and δ) were well tolerated in the reaction. Finally, the synthetic versatility of the Hartung-Mukaiyama cyclization was demonstrated through a stereocontrolled synthesis of the tetrahydrofuran moiety of amphidinolide N, a potent cytotoxic macrolide of marine origin. This study expands the capacity of Mukaiyama-type cyclization in that it can be used in convergent assembly of complex tetrahydrofuran motifs from internal olefins.