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The administration of venetoclax (Ven) with azacitidine (Aza) was used as induction or salvage therapy for 34 patients with acute myeloid leukemia (AML) in our institute. An itraconazole oral solution (ITCZ-OS) was administered to 17 patients (50%) as antifungal prophylaxis. The trough concentration of Ven was significantly higher in patients treated with ITCZ than in those who were not (median values, 1.31 μg/mL vs. 0.64 μg/mL; p = 0.0072). Ven concentrations were > 3 μg/mL in some patients treated with ITCZ and the patient with the highest Ven concentration (5.58 μg/mL) expired after grade 4 neutropenia persisted for more than 50 days after the 1st cycle of Ven/Aza. It was also found that the group with concentrations equal to or above 1.29 μg/mL showed a significantly higher rate of achieving CR or CRi (p = 0.039). In conclusion, the measurement of Ven concentrations in AML cases is essential in daily clinical practice, particularly in those receiving antifungal prophylaxis. [ABSTRACT FROM AUTHOR]

The Japanese Society of Hematology performed an observational cross-sectional study to clarify the morbidity, prognosis, and prognostic factors in patients with COVID-19 with hematological diseases (HDs) in Japan. The study included patients with HDs who enrolled in our epidemiological survey and had a COVID-19 diagnosis and a verified outcome of up to 2 months. The primary endpoints were characteristics and short-term prognosis of COVID-19 in patients with HDs. A total of 367 patients from 68 institutes were enrolled over 1 year, and the collected data were analyzed. The median follow-up among survivors was 73 days (range, 1–639 days). The 60-day overall survival (OS) rate was 86.6%. In the multivariate analysis, albumin ≤ 3.3 g/dL and a need for oxygen were independently associated with inferior 60-day OS rates (hazard ratio [HR] 4.026, 95% confidence interval (CI) 1.954–8.294 and HR 14.55, 95% CI 3.378–62.64, respectively), whereas 60-day survival was significantly greater in patients with benign rather than malignant disease (HR 0.095, 95% CI 0.012–0.750). Together, these data suggest that intensive treatment may be necessary for patients with COVID-19 with malignant HDs who have low albumin levels and require oxygen at the time of diagnosis. [ABSTRACT FROM AUTHOR]

The behavior of hole polarons in β -gallium oxide (Ga2O3) has attracted significant attention. Depth-resolved cathodoluminescence (CL) was used to investigate the minority carrier dynamics in β -Ga2O3. First, a model describing CL intensity was proposed by considering the depth-dose function and surface recombination. A universal depth-dose function for β -Ga2O3, which has the form of a third-degree polynomial, was presented based on Monte Carlo simulation by introducing a normalized depth, which is the depth normalized by the electron beam range. Second, two experimental approaches, plan-view and cross-sectional CL measurements, were applied to unintentionally doped β -Ga2O3 (âˆ'201) wafers, and the experimental results were compared with those of the proposed model. The hole diffusion length was estimated to be within the range of 200â€"400 nm through the plan-view measurement, whereas a hole diffusion length of 250 nm was obtained through the cross-sectional measurement. The values were consistent with each other, and the model reproduced the experimental results well. This indicates that the nonequilibrium minority hole in the unintentionally doped β -Ga2O3 is mobile and forms a ‘weak’ polaron. The reduced recombination velocity of the (âˆ'201) face was estimated to be approximately ten for the plan-view measurement, whereas that of ten or more was assumed for the cross-sectional measurement. No inconsistency was observed, but the low-energy plan-view measurement is considered more suitable for investigating the surface recombination velocity. [ABSTRACT FROM AUTHOR]

Our previous clinical study has shown that the exopolysaccharide (EPS) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, improves chronic allergy status in humans. In addition, an inhibition of visceral fat accumulation was observed following the intake of EPS during animal experimentation. In the present study, we have further evaluated the health-promoting effects of a spray-dried powder of pineapple juice that is fermented with the IJH-SONE68 strain. This was conducted in a double-blind, randomized, placebo-controlled, parallel-group clinical trial at Hiroshima University from May 2019 to July 2021. Eighty healthy volunteers at range of ages 23–70, with a body mass index between 25 and 29.99, were enrolled. After the 12 weeks of the experimental period were complete, although the average visceral fat area in both groups similarly decreased, there was no significant difference in the content of visceral fat area or in the obesity-related physical parameters in both groups. Further, we found that the serum liver function indices (AST and ALT) in the test group decreased within a statistically determined trend (p = 0.054). The fecal microflora analysis revealed, in the test group, a statistically significant increase in the relative abundance changes within Anaerostipes, which has been reported to help suppress hepatic inflammation. [ABSTRACT FROM AUTHOR]

Aims: Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). Methods and results: This single‐centre observational study included 142 patients with HF who underwent CA for AF (median follow‐up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all‐cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person‐years, vs. systolic HF: 28%, 6.6/100 person‐years, P = 0.18; last procedure: 20%, 4.8/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person‐years, vs. 24%, 5.7/100 person‐years, P = 0.07; last procedure: 11%, 2.5/100 person‐years, vs. 24%, 6.9/100 person‐years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person‐years, vs. 5%, 1.2/100 person‐years, P = 0.74; last procedure: 6%, 1.4/100 person‐years, vs. 2%, 0.5/100 person‐years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre‐CA, vs. 0 hospitalizations [0, 0] in post‐CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). Conclusions: CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients. [ABSTRACT FROM AUTHOR]

What is known and objective: It was previously reported that the incidence of lenalidomide (LEN)‐induced skin rash is reduced by administration of bortezomib (BOR) prior to LEN administration in patients with multiple myeloma (MM). Therefore, we investigated whether LEN‐induced skin rash is affected by the duration of BOR administration and the dosing interval between BOR and LEN administration. Method: A retrospective investigation was conducted among MM patients who received BOR treatment prior to LEN treatment in Eiju General Hospital from May 2010 to December 2020. We investigated whether the BOR administration duration and interval duration from the completion of BOR administration to the initial LEN administration affect the development of LEN‐induced skin rash. Result and discussion: Twenty‐eight of the 81 patients exhibited LEN‐induced skin rash (34.6%). The administered duration, but not the interval, was significantly longer in the group without skin rash. Cut‐off values were set for the duration of administration and interval, which were 35 days and 30 days, respectively. Multivariate analysis was performed on patients which are administered duration of more than 35 days and intervals of less than 30 days, and those who are not applicable. A significant difference was observed in the incidence of skin rash for each factor. What is new and conclusion: The risk of reduced LEN‐induced skin rash is affected not only by the presence of prior BOR administration, but also by the duration of BOR and the interval from the completion of BOR to the initial LEN administration. [ABSTRACT FROM AUTHOR]

Long-duration atrial high-rate episodes (AHREs) monitored using cardiac implantable electronic devices (CIEDs) can predict long-term major adverse cardiovascular events (MACEs). This study aimed to compare the impact of long-duration AHRE on MACE development between patients with and without a history of atrial fibrillation (AF). This single-center observational study included 132 CIED-implanted patients with AHREs detected via remote monitoring. The population was dichotomized into groups: with (n = 69) and without (n = 63) AF. In each group, cumulative incidences of MACEs comprising all-cause deaths, heart failure hospitalizations, strokes, and acute coronary syndromes were compared between patients with AHRE durations of ≥24 h and <24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE ≥24 h than in those with <24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE ≥24 h and <24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of ≥24 h emerged as the only independent predictor of MACEs among patients without AF (p = 0.03). In conclusion, a long-duration AHRE was prognostic in patients without a history of AF but not in patients with a history of AHREs. [ABSTRACT FROM AUTHOR]

Assays using ELISA measurements on serially diluted serum samples have been heavily used to measure serum reactivity to SARS-CoV-2 antigens and are widely used in virology and elsewhere in biology. We test a method using Bayesian hierarchical modelling to reduce the workload of these assays and measure reactivity of SARS-CoV-2 and HCoV antigens to human serum samples collected before and during the COVID-19 pandemic. Inflection titers for SARS-CoV-2 full-length spike protein (S1S2), spike protein receptor-binding domain (RBD), and nucleoprotein (N) inferred from 3 spread-out dilutions correlated with those inferred from 8 consecutive dilutions with an R2 value of 0.97 or higher. We confirm existing findings showing a small proportion of pre-pandemic human serum samples contain cross-reactive antibodies to SARS-CoV-2 S1S2 and N, and that SARS-CoV-2 infection increases serum reactivity to the beta-HCoVs OC43 and HKU1 S1S2. In serial dilution assays, large savings in resources and/or increases in throughput can be achieved by reducing the number of dilutions measured and using Bayesian hierarchical modelling to infer inflection or endpoint titers. We have released software for conducting these types of analysis. [ABSTRACT FROM AUTHOR]

Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment. [ABSTRACT FROM AUTHOR]

Patients with cancer are considered at high risk of acquiring coronavirus disease (COVID-19). To identify patients who are likely to be diagnosed with severe COVID-19, we analyzed the risk factors for mortality in patients admitted to the hematology department at our institute. The mortality rate of all patients was as high as 62% (21 of the 34 patients), and most of these patients had malignant malignancies. Patients before an achievement of remission had a 10.8-fold higher risk of death than those in remission. The group receiving chemotherapy with steroids had a shorter survival time and had an 8.3-fold higher risk of death than that receiving chemotherapy without steroids. During the COVID-19 pandemic, it is necessary to carefully monitor or follow-up patients with active diseases and patients receiving steroid-containing chemotherapy. [ABSTRACT FROM AUTHOR]

What is known and objective: Skin rash is one of the typical side effects of lenalidomide (LEN) treatment. Desensitization therapies have been reported to be effective in patients with severe skin rash caused by LEN. However, they have proved impractical due to the complexity of the protocols. Case summaries: We present 5 patients who developed severe LEN‐induced skin rash. The five patients received our simple, slow desensitization protocol, and all were re‐administered LEN with no adverse reaction. What is new and Conclusion: Our simpler and slow desensitization protocol, which desensitizes the patients without reducing the effect of LEN, includes drug holidays, similar to the usual LEN dosing schedule, and moreover is recommended as a treatment option especially for elderly patients with no housemate to help with medical management. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify the risk factors for lenalidomide (Len)-associated skin rash. We retrospectively investigated the medical records of 144 multiple myeloma patients treated with Len-containing therapies. A total of 64 of 144 patients included in the study had skin rash (44.4%). 50 patients developed skin rash within 4 weeks of starting Len treatment. Further, in 29 patients, the skin rash appeared at an early stage (within 1 week) after treatment initiation. Univariate analysis revealed that the risk of skin rash significantly increased in patients with advanced age (p = 0.017), myeloma subtype (p = 0.014), no prior chemotherapy (p = 0.012), and Len dosage (p = 0.008). Multivariate logistic regression analysis demonstrated that advanced age (≥ 70 years), BJP-subtype of myeloma and no prior chemotherapy were significant risk factors for the skin rash associated with Len. Thus, patients with these risk factors should be carefully monitored for the appearance of skin rash during the treatment with Len. [ABSTRACT FROM AUTHOR]

Low-energy cross-sectional cathodoluminescence (CL) with a beam energy of 1 keV was applied to Si-ion-implanted β-Ga2O3 (−201) wafers to investigate implantation damage and recovery. The semi-quantitative CL-intensity depth profiles were obtained by considering nonradiative recombination at the surface. We found that the CL intensity did not fully recover, even after annealing at 1273 K. Such insufficient recovery was prominent in the Si-diffusion region, suggesting that Si-dopant activation and Si diffusion are strongly correlated through interaction with point defects generated by implantation, such as Si interstitials and Ga vacancies. [ABSTRACT FROM AUTHOR]

We performed cross-sectional cathodoluminescence (CL) for gallium nitride (GaN)-based high electron mobility transistors (HEMTs) to investigate process-induced defects. The cross-sectional CL measurements at room temperature clearly show the intensity distribution for the 25 nm-thick AlGaN layer, even though it is very thin. We also observed that the intensities of the band-edge emissions from the AlGaN and GaN layers fall near the source and drain regions. Those intensity decays demonstrate that ion implantation at the source and drain regions generates many nonradiative recombination centers and that these defects are not eliminated even by activation annealing after ion implantation. We also observed that the intensity of yellow luminescence (YL) in the GaN layer drops not only at the source and drain regions, but also in deeper regions of the 1.4 μm-thick GaN layer. We consider diffusion of the implantation-generated defects and their interactions with point defects in this deep region, which are responsible for the YL, to be the mechanism responsible for the YL intensity decrease. Ion implantation and subsequent annealing not only activates the dopant atoms, but also changes the point defects, which may affect the device characteristics. These findings show that cross-sectional CL spectral mapping can visualize the process-induced defects in GaN HEMTs and can therefore be used for process optimization and failure analysis of these devices. [ABSTRACT FROM AUTHOR]

Bone turnover markers (BTMs) are useful parameters for assessing fracture risk and unlike bone mineral density (BMD), can be measured at any institution. However, BTM values have not been established in patients post-allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the practicality of BTMs in patients who underwent allo-HSCT by measuring levels of the serum bone resorption marker, tartrate-resistant acid phosphatase-5b (TRACP-5b), and the bone formation marker, bone-specific alkaline phosphatase (BAP), together with BMD, 1 month before and 6 months after allo-HSCT. Patients were classified into either the alendronate group (n = 14) if alendronate treatment (35 mg orally per week) was administered before allo-HSCT or within 1 month after allo-HSCT, or the control group (n = 16), in which patients did not receive alendronate treatment. Despite the high frequency of corticosteroids users in the alendronate group (71.4 vs. 18.9%; p < 0.01), the mean percentage changes in BMD at the lumbar spine (− 2.9 vs. − 3.1%; p = 0.44) and femoral neck (− 3.2 vs. − 4.1%; p = 1.00), TRACP-5b levels (− 4.8 vs. 9.9%; p = 0.45), and BAP levels (6.9 vs. 1.0%; p = 0.85) during 6 months did not differ significantly between the alendronate and control groups. Additionally, the percentage changes in BMD at the lumbar spine were negatively associated with the TRACP-5b levels 6 months after allo-HSCT (p = 0.03, r = 0.40). Our results indicate the possible effectiveness of alendronate treatment in allo-HSCT patients. BTM levels could be useful to monitor the BMD changes. [ABSTRACT FROM AUTHOR]

It is well known that the second-generation tyrosine kinase inhibitor dasatinib evokes an immunological reaction as an off-target effect and induces large granular lymphocytes (LGLs) expansion in 30% of patients. However, LGLs expansion in nilotinib-treated patients is rare. We report the case of a 65-year-old patient with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) who showed LGLs expansion during nilotinib treatment. The patient achieved complete remission (CR) after multi-agent chemotherapy combined with dasatinib treatment. However, ALL relapsed in the central nervous system and bone marrow when treatment was interrupted due to interstitial pneumonia. Nilotinib treatment was subsequently started and the patient achieved second CR. Marked peripheral blood lymphocytosis emerged after the start of nilotinib treatment. CD8 + CD57 + cytotoxic T cells were predominantly expanded and showed strong cytocidal activity against K562 Ph-positive leukemia cells. These results suggest that similar to dasatinib, nilotinib can induce LGLs expansion, possibly contributing to long-term remission in patients with Ph-ALL. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the outcomes of patients with acute undifferentiated leukemia after allogeneic hematopoietic stem cell transplantation. The patients were given intravenous infusion of donor hematopoietic stem cells, and acute graft-versus-host disease (GVHD) prophylaxis with cyclosporine or tacrolimus and short-term methotrexate.

We propose aggregative context-aware fitness functions based on feature selection for evolutionary learning of characteristic graph patterns. The proposed fitness functions estimate the fitness of a set of correlated individuals rather than the sum of fitness of the individuals, and specify the fitness of an individual as its contribution degree in the context of the set. We apply the proposed fitness functions to our evolutionary learning, based on Genetic Programming, for obtaining characteristic block-preserving outerplanar graph patterns and characteristic TTSP graph patterns from positive and negative graph data. We report some experimental results on our evolutionary learning of characteristic graph patterns, using the context-aware fitness functions. [ABSTRACT FROM AUTHOR]

An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM). The patient received lenalidomide plus dexamethasone therapy but died due to exacerbation of the disorder. It was supposed that thrombocytopenia was secondarily caused by CMML and MM developed at a later period. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis and frequent progression to leukemia. It has long remained unresolved how MDS cells, which are less proliferative, inhibit normal hematopoiesis and eventually dominate the bone marrow space. Despite several studies implicating mesenchymal stromal or stem cells (MSCs), a principal component of the HSC niche, in the inhibition of normal hematopoiesis, the molecular mechanisms underlying this process remain unclear. Here, we demonstrate that both human and mouse MDS cells perturb bone metabolism by suppressing the osteolineage differentiation of MSCs, which impairs the ability of MSCs to support normal HSCs. Enforced MSC differentiation rescues the suppressed normal hematopoiesis in both in vivo and in vitro MDS models. Intriguingly, the suppression effect is reversible and mediated by extracellular vesicles (EVs) derived from MDS cells. These findings shed light on the novel MDS EV-MSC axis in ineffective hematopoiesis. [Display omitted] • Normal hematopoiesis is indirectly and profoundly impaired in MDS • MSCs in MDS are less supportive to normal HSCs • MDS cells inhibit osteolineage differentiation of MSCs via MDS-derived EVs • Osteogenic differentiation of MSCs contributes to the recovery of hematopoiesis Hayashi et al. show that MDS cells impair osteolineage differentiation of MSCs via MDS-derived EVs, leading to bone marrow failure due to less supportive niche function. Indeed, enforced differentiation of MSCs or EV inhibition rescues the normal hematopoiesis. These findings highlight cancer-derived EVs and MSC axis in MDS pathogenesis. [ABSTRACT FROM AUTHOR]

Glioblastomas are the most aggressive brain tumors. Glioblastoma stem cells ( GSCs) are thought to be responsible for the recurrence, chemoresistance, and poor prognosis of glioblastoma. Fatty acid binding protein 7 ( FABP7), which is a cellular chaperone for a variety of omega-3 fatty acids, is a known marker for neural stem cells. In this study, using a newly developed anti- FABP7 antibody and patient-derived GSC lines, we evaluated the expression of FABP7 in GSCs. Using immunocytochemistry, Western blotting, and qPCR analyses, FABP7 was found to be highly enriched in GSCs and its localization was found in cytosol and nuclei. FABP7 expression was significantly downregulated in differentiated GSCs induced by the addition of serum. In the glioma surgical specimens, FABP7 was highly expressed in the majority of glioblastoma. Double immunostaining for FABP7 and Sox2 showed that FABP7+ Sox2+ tumor cells were significantly increased in glioblastoma (grade IV) compared with diffuse astrocytoma (grade II) and anaplastic astrocytoma (grade III). Our data introduces FABP7 as a marker for GSCs and further highlights its possible significance for glioma diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Activating mutations of c-Kit are frequently found in acute myeloid leukemia (AML) patients harboring t(8;21) chromosomal translocation generating a fusion protein AML1-ETO. Here we show that an active mutant of c-Kit cooperates with AML1-ETO to induce AML in mouse bone marrow transplantation models. Leukemic cells expressing AML1-ETO with c-Kit were serially transplantable. Transplantation experiments indicated that lineagec-KitSca-1 (KSL) leukemic cells, but not lineage leukemic cells, were enriched for leukemia stem cells (LSCs). Comparison of gene expression profiles between KSL leukemic and normal cells delineated that CD200R1 was highly expressed in KSL leukemic cells as compared with KSL normal cells. Upregulation of CD200R1 was verified in lineage leukemic cells, but not in lineage leukemic cells. CD200R1 expression in the lineage leukemic cells was not correlated with the frequency of LSCs, indicating that CD200R1 is not a useful marker for LSCs in these models. Interestingly, CD200R1 was upregulated in KSL cells transduced with AML1-ETO, but not with other leukemogenic mutants, including c-Kit, AML1, and AML1. Consistently, upregulation of CD200R1 in lineage leukemic cells was observed only in the BM of mice suffering from AML1-ETO-positive leukemia. In conclusion, AML1-ETO upregulated CD200R1 in lineage cells, which was characteristic of AML1-ETO-positive leukemia in mice. [ABSTRACT FROM AUTHOR]

The Bcr-Abl oncogene causes human Philadelphia chromosome-positive (Ph) leukemias, including B-cell acute lymphoblastic leukemia (B-ALL) and chronic myeloid leukemia (CML) with chronic phase (CML-CP) to blast crisis (CML-BC). Previous studies have demonstrated that Src family kinases are required for the induction of B-ALL, but not for CML, which is induced by Bcr-Abl in mice. In contrast, it has been reported that Fyn is up-regulated in human CML-BC compared with CML-CP, implicating Fyn in the blast crisis transition. Here, we aimed to delineate the exact role of Fyn in the induction/progression of Ph leukemias. We found that Fyn is expressed in mouse hematopoietic cells at varying stages of development, including c-kitSca-1Lin cells. Notably, Fyn is highly expressed in some of human lymphomas, but not in human Ph leukemias including CML-BC. In mouse bone marrow transplantation models, mice transplanted with wild-type or Fyn-deficient bone marrow cells transduced with Bcr-Abl showed no differences in the development of B-ALL or CML-like diseases. Similarly, Fyn deficiency failed to impact the development of myeloid CML-BC induced by Bcr-Abl and Hes1. Elevated expression of Fyn was not found in mouse samples of Bcr-Abl-mediated CML- and CML-BC-like diseases. Thus, Fyn is not required for the pathogenesis of Bcr-Abl-mediated leukemias. [ABSTRACT FROM AUTHOR]

Recently, due to the rapid growth of electronic data having graph structures such as HTML and XML texts and chemical compounds, many researchers have been interested in data mining and machine learning techniques for finding useful patterns from graph-structured data (graph data). Since graph data contain a huge number of substructures and it tends to be computationally expensive to decide whether or not such data have given structural features, graph mining problems face computational difficulties. Let ${\mathcal{C}}$ be a graph class which satisfies a connected hereditary property and contains infinitely many different biconnected graphs, and for which a special kind of the graph isomorphism problem can be computed in polynomial time. In this paper, we consider learning and mining problems for ${\mathcal{C}}$ . Firstly, we define a new graph pattern, which is called a block preserving graph pattern (bp-graph pattern) for ${\mathcal{C}}$ . Secondly, we present a polynomial time algorithm for deciding whether or not a given bp-graph pattern matches a given graph in ${\mathcal{C}}$ . Thirdly, by giving refinement operators over bp-graph patterns, we present a polynomial time algorithm for finding a minimally generalized bp-graph pattern for ${\mathcal{C}}$ . Outerplanar graphs are planar graphs which can be embedded in the plane in such a way that all of vertices lie on the outer boundary. Many pharmacologic chemical compounds are known to be represented by outerplanar graphs. The class of connected outerplanar graphs ${\mathcal{O}}$ satisfies the above conditions for ${\mathcal{C}}$ . Next, we propose two incremental polynomial time algorithms for enumerating all frequent bp-graph patterns with respect to a given finite set of graphs in ${\mathcal{O}}$ . Finally, by reporting experimental results obtained by applying the two graph mining algorithms to a subset of the NCI dataset, we evaluate the performance of the two graph mining algorithms. [ABSTRACT FROM AUTHOR]

We have developed a miniaturized microfluidic culture system that allows experimentation on individual human embryonic stem cell (hESC) colonies in dynamic (flow applied) or static (without flow) conditions. The system consists of three inlet channels that converge into a cell-culture channel and provides the capability to spatially and temporally deliver specific treatments by using patterned laminar fluid flow to different parts of a single hESC colony. We show that microfluidic culture for 96 h with or without flow results in similar maintenance of hESC self-renewal, the capability to differentiate into three germ cell lineages, and to maintain a normal karyotype, as in standard culture dishes. Localized delivery of a fluorescent nucleic acid dye was achieved with laminar flow, producing staining only in nuclei of exposed cells. Likewise, cells in desired regions of colonies could be removed with enzymatic treatment and collected for analysis. Re-coating the enzyme treated area of the channel with extracellular matrix led to re-growth of hESC colonies into this region. Our study demonstrates the culture of hESCs in a microfluidic device that can deliver specific treatments to desired regions of a single colony. This miniaturized culture system allows in situtreatment and analysis with the ability to obtain cell samples from part of a colony without micromanipulation and to perform sensitive molecular analysis while permitting further growth of the hESC colony. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract. IBD includes Crohn's disease (CD) and ulcerative colitis (UC). CD can occur in any part of the gastrointestinal tract, whereas UC mainly occurs in the colon and rectum. We previously demonstrated that a novel exopolysaccharide (EPS) produced by a plant-derived bacterium, Lactobacillus paracasei IJH-SONE68, prevents and improves the inflammation in contact dermatitis model mice via oral administration. To evaluate the preventive effect of the EPS against other inflammatory diseases, in the present study, we employed dextran sulfate sodium (DSS)-induced UC model mice. The stool consistency, hematochezia, and colonic atrophy of the mice were improved by the orally administered EPS. We also evaluated the cytokine transcription. Overexpression of the mouse macrophage inflammatory protein 2 mRNA in the colon as a functional homolog of human interleukin-8 was decreased by the orally administered EPS. However, the expression of interleukin-10, which is known as an anti-inflammatory cytokine, was stimulated in the EPS-administrated group. Based on these results, we conclude that the IJH-SONE68-derived EPS is a promising lead material for the development of drugs useful in treating inflammatory diseases such as UC. [ABSTRACT FROM AUTHOR]

We propose the in situ formation of gel microbeads made of a thermoreversible hydrogel for indirect laser micromanipulation of microorganisms. Irradiation, using a 1064 nm laser, of an aqueous solution mixed with poly-(N-isopropylacrylamide) through a high magnification lens resulted in the formation of a gel microbead at the laser focus due to heating. The gel microbead is trapped by the laser, and is used for indirect laser micromanipulation of microorganisms. However, the laser power used to form the bead is generally too strong to perform manipulation in a stable manner. In this letter we show a method to reduce the laser power to form a gel microbead using the poly-(N-isopropylacrylamide) aqueous solution by the addition of additives. The gelation temperature and the laser absorption rate of the solution in the presence of several different additives were investigated. We selected YPD (yeast extract, peptone, dextrose) broth as an additive and measured the relationship between the laser power, irradiation time, and diameter of the gel microbead. We succeeded in reducing the laser power for gel microbead formation, and in using the laser-trapped gel microbead for the manipulation of a yeast cell and DNA. [ABSTRACT FROM AUTHOR]