Publications by authors named "Satoshi Takahashi"

732 Publications

Hematological effects on peri-transplant use of linezolid in adults undergoing single-unit cord blood transplantation.

Ann Hematol 2021 Jul 17. Epub 2021 Jul 17.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

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http://dx.doi.org/10.1007/s00277-021-04597-7DOI Listing
July 2021

Cord blood index predicts engraftment and early non-relapse mortality in adult patients with single-unit cord blood transplantation.

Bone Marrow Transplant 2021 Jul 15. Epub 2021 Jul 15.

Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan.

How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels. The CBI defined three groups that had different neutrophil engraftment rates at day 30 (High, 83.7% [95% CI, 79.2-88.1%]; Intermediate, 77.0% [95% CI, 73.7-80.2%]; Low, 68.4% [95% CI, 63.6-73.2%]), platelet engraftment rates at day 60 (High, 70.4% [95% CI, 64.9-75.9%]; Intermediate, 62.3% [95% CI, 58.5-66.0%]; Low, 49.3% [95% CI, 44.2-54.5%]), and non-relapse mortality at day 100 (High, 14.1% [95% CI, 9.9-18.3%]; Intermediate, 16.4% [95% CI, 13.5-19.3%]; Low, 21.3% [95% CI, 17.1-25.5%]). This novel approach is clinically beneficial and can be adopted immediately because it uses easily obtained pre-freeze data of CB.
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http://dx.doi.org/10.1038/s41409-021-01406-7DOI Listing
July 2021

Evaluation of false positives in the SARS-CoV-2 quantitative antigen test.

J Infect Chemother 2021 Jun 25. Epub 2021 Jun 25.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan; Division of Infection Control, Sapporo Medical University Hospital, Sapporo, Japan; Department of Infection Control and Laboratory Medicine Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Introduction: Highly sensitive reagents for detecting SARS-CoV-2 antigens have been developed for accurate and rapid diagnosis till date. In this study, we aim to clarify the frequency of false-positive reactions and reveal their details in SARS-CoV-2 quantitative antigen test using an automated laboratory device.

Methods: Nasopharyngeal swab samples (n = 4992) and saliva samples (n = 5430) were collected. We measured their SARS-CoV-2 antigen using Lumipulse® Presto SARS-CoV-2 Ag and performed a nucleic acid amplification test (NAAT) using the Ampdirect™ 2019 Novel Coronavirus Detection Kit as needed. The results obtained from each detection test were compared accordingly.

Results: There were 304 nasopharyngeal samples and 114 saliva samples were positive in the Lumipulse® Presto SARS-CoV-2 Ag test. All positive nasopharyngeal samples in the antigen test were also positive for NAAT. In contrast, only three (2.6%) of all the positive saliva samples in the antigen test were negative for NAAT. One showed no linearity with a dilute solution in the dilution test. Additionally, the quantitative antigen levels of all the three samples did not decrease after reaction with the anti-SARS-CoV-2 antibody.

Conclusions: The judgment difference between the quantitative antigen test and NAAT seemed to be caused by non-specific reactions in the antigen test. Although the high positive and negative predictive value of this quantitative antigen test could be confirmed, we should consider the possibility of false-positives caused by non-specific reactions and understand the characteristics of antigen testing. We recommend that repeating centrifugation before measurement, especially in saliva samples, should be performed appropriately.
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http://dx.doi.org/10.1016/j.jiac.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226058PMC
June 2021

Analysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation.

Cancers (Basel) 2021 Jun 1;13(11). Epub 2021 Jun 1.

Department of Public Health and Preventive Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.

Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, , , , and , and two SNPs in the methylase genes, and , in 999 uBMT donor-recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes ( > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low -value in regression analysis of grade 2-4 acute graft-versus-host disease ( = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.
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http://dx.doi.org/10.3390/cancers13112752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199545PMC
June 2021

Momentum of neutrophil recovery using an exponential growth model predicts the prognosis of single cord blood transplantation.

Int J Lab Hematol 2021 Jun 29. Epub 2021 Jun 29.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Introduction: After the first appearance of peripheral blood neutrophils, recipients from adult donor sources have a rapid increase in neutrophil recovery, whereas cord blood transplantation (CBT) recipients have a slow increase. However, the momentum of neutrophil recovery after CBT varies widely among individuals, but optimal methods to evaluate the momentum of neutrophil recovery and their clinical impacts are yet to be clarified.

Methods: We retrospectively examined the prognostic effect of the momentum of neutrophil recovery in the last 7 days until neutrophil engraftment, which was calculated by an exponential growth model, after single CBT following myeloablative conditioning for 207 adults.

Results: Among patients who achieved each hematopoietic lineage recovery by day 100, the momentum of neutrophil recovery, which was represented as a growth constant, was associated with the day of neutrophil engraftment (P < .0001), red blood cell engraftment (P < .0001), and platelet engraftment (P < .0001) using the Spearman's rank correlation coefficient test. More importantly, overall survival was superior with a higher growth constant compared with a lower growth constant (P < .001). In the multivariate analysis, a higher growth constant showed a lower overall mortality compared with a lower growth constant (hazard ratio: 0.48, P = .014).

Conclusion: Our data demonstrated that the momentum of neutrophil recovery during the last 7 days before neutrophil engraftment, which was measured using an exponential growth model, was associated not only with hematopoietic recovery but also with a better prognosis after single CBT.
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http://dx.doi.org/10.1111/ijlh.13636DOI Listing
June 2021

Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study.

J Infect Chemother 2021 Jun 24. Epub 2021 Jun 24.

Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Introduction: In quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases.

Methods: In this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation.

Results: In total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010).

Conclusions: Patients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.
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http://dx.doi.org/10.1016/j.jiac.2021.06.009DOI Listing
June 2021

Novel Indicators of Transplant Outcomes for PhALL: Current Molecular-Relapse-Free Survival.

Transplant Cell Ther 2021 Jun 24. Epub 2021 Jun 24.

Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan. Electronic address:

Molecular relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has been thought to predict clinical relapse in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (PhALL). Tyrosine kinase inhibitor (TKI) administration after allo-HCT may dynamically change the status from molecular relapse to molecular remission, but these state changes cannot be accurately represented by conventional survival indicators such as relapse-free survival, where events are usually considered irreversible. We aimed to develop novel indicators of transplant outcomes for allo-HCT recipients with PhALL and to visualize current molecular-relapse-free survival (CMRFS) and current on-TKI status (CTKI), treating molecular relapse or TKI administration after allo-HCT as a reversible event. We retrospectively analyzed 286 patients with PhALL who received allo-HCT between 2000 and 2016 in order to develop the indicators. CMRFS was defined as the probability of molecular remission without clinical relapse or death at any time after allo-HCT. Similarly, CTKI was defined as the probability of TKI administration without clinical relapse or death at any time after allo-HCT. The 1- and 5-year CMRFS rates were 67% and 59%, respectively, whereas the 1- and 5-year conventional molecular relapse-free survival rates were 42% and 37%. The 1- and 5-year CTKI rates were 14% and 8%, respectively. In a post hoc analysis focusing on patients who had achieved a molecular complete remission within 6 weeks (n = 201), the 5-year CMRFS rate (71%) was similar to the 5-year conventional molecular relapse-free survival (molRFS) rate (70%) in the non-TKI group. On the other hand, the 5-year CMRFS rate in the TKI group was 61%, whereas the 5-year conventional molRFS rate was only 38%. CMRFS and CTKI might become useful indicators of transplant success in terms of survival, leukemia-free status, and treatment-free status at any time point. Future extension of these survival models to other clinical situations is warranted.
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http://dx.doi.org/10.1016/j.jtct.2021.06.020DOI Listing
June 2021

Characterization of Histone H3 Lysine 4 and 36 Tri-methylation in L.

Front Plant Sci 2021 7;12:659634. Epub 2021 Jun 7.

Graduate School of Agricultural Science, Kobe University, Kobe, Japan.

Covalent modifications of histone proteins act as epigenetic regulators of gene expression. We report the distribution of two active histone marks (H3K4me3 and H3K36me3) in 14-day leaves in two lines of L. by chromatin immunoprecipitation sequencing. Both lines were enriched with H3K4me3 and H3K36me3 marks at the transcription start site, and the transcription level of a gene was associated with the level of H3K4me3 and H3K36me3. H3K4me3- and H3K36me3-marked genes showed low tissue-specific gene expression, and genes with both H3K4me3 and H3K36me3 had a high level of expression and were constitutively expressed. Bivalent active and repressive histone modifications such as H3K4me3 and H3K27me3 marks or antagonistic coexistence of H3K36me3 and H3K27me3 marks were observed in some genes. Expression may be susceptible to changes by abiotic and biotic stresses in genes having both H3K4me3 and H3K27me3 marks. We showed that the presence of H3K36me3 marks was associated with different gene expression levels or tissue specificity between paralogous paired genes, suggesting that H3K36me3 might be involved in subfunctionalization of the subgenomes.
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http://dx.doi.org/10.3389/fpls.2021.659634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215614PMC
June 2021

Extracellular mRNA transported to the nucleus exerts translation-independent function.

Nat Commun 2021 06 16;12(1):3655. Epub 2021 Jun 16.

Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, School of Medicine, Matsumoto, Nagano, Japan.

RNA in extracellular vesicles (EVs) are uptaken by cells, where they regulate fundamental cellular functions. EV-derived mRNA in recipient cells can be translated. However, it is still elusive whether "naked nonvesicular extracellular mRNA" (nex-mRNA) that are not packed in EVs can be uptaken by cells and, if so, whether they have any functions in recipient cells. Here, we show the entrance of nex-mRNA in the nucleus, where they exert a translation-independent function. Human nex-interleukin-1β (IL1β)-mRNA outside cells proved to be captured by RNA-binding zinc finger CCCH domain containing protein 12D (ZC3H12D)-expressing human natural killer (NK) cells. ZC3H12D recruited to the cell membrane binds to the 3'-untranslated region of nex-IL1β-mRNA and transports it to the nucleus. The nex-IL1β-mRNA in the NK cell nucleus upregulates antiapoptotic gene expression, migration activity, and interferon-γ production, leading to the killing of cancer cells and antimetastasis in mice. These results implicate the diverse actions of mRNA.
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http://dx.doi.org/10.1038/s41467-021-23969-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208975PMC
June 2021

Prognostic impacts of peripheral blood erythroblasts after single-unit cord blood transplantation.

Int J Lab Hematol 2021 Jun 12. Epub 2021 Jun 12.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Introduction: The appearance of erythroblasts (EBLs) in peripheral blood occurs in a variety of serious conditions and has been associated with mortality in critically ill patients. However, the incidence, risk factor, and outcomes of EBLs after cord blood transplantation (CBT) remain unclear.

Methods: We have investigated the impact of EBLs on transplant outcomes on 225 adult patients who underwent single-unit CBT at our single institute.

Results: The cumulative incidences of EBL ≥200 × 10 /L and EBL ≥1000 × 10 /L at 60 days after CBT were 17% and 4%, respectively, detected after a median of 35 days and 36.5 days. Multivariate analysis using erythroblastosis as time-dependent covariates demonstrated the significant association of EBL ≥1000 × 10 /L, but not EBL ≥200 × 10 /L, with the development of grade III-IV acute graft-versus-host disease (GVHD, hazard ratio [HR]: 18.56; P < .001), higher nonrelapse mortality (HR: 13.38; P < .001), and overall mortality (HR: 4.97; P = .001).

Conclusion: These data suggested that higher levels of EBLs were recognized as a significant risk factor for severe acute GVHD and mortality after single-unit CBT. Higher levels of EBLs may serve as a surrogate marker for poor single CBT outcomes.
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http://dx.doi.org/10.1111/ijlh.13622DOI Listing
June 2021

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

Clin Exp Nephrol 2021 Jun 7. Epub 2021 Jun 7.

Department of Urology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.

Background: Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD.

Methods: Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 μg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared.

Results: The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 μg/g Cr vs. 2.0 μg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group.

Conclusions: L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.
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http://dx.doi.org/10.1007/s10157-021-02088-7DOI Listing
June 2021

Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease.

J Echocardiogr 2021 Jun 5. Epub 2021 Jun 5.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan.

Background: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD.

Methods: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected.

Results: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD.

Conclusions: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.
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http://dx.doi.org/10.1007/s12574-021-00532-xDOI Listing
June 2021

Effects of localisation of uterine adenomyosis on outcome of in vitro fertilisation/intracytoplasmic sperm injection fresh and frozen-thawed embryo transfer cycles: a multicentre retrospective cohort study.

Reprod Biol Endocrinol 2021 Jun 4;19(1):84. Epub 2021 Jun 4.

Department of Obstetrics and Gynecology, Akita University Graduate School of Medicine, 010-8543, Akita, Japan.

Background: Uterine adenomyosis is a benign disease, common among women in their 40 and 50 s, characterised by ectopic endometrial tissue in the uterine myometrial layer. Adenomyosis causes infertility and has a negative effect on the outcomes of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles. It has also been reported to have different characteristics depending on the adenomyotic lesion localisation. The effect of its localisation on IVF/ICSI-ET outcomes is unclear. This study aimed to investigate whether adenomyotic lesion localisation, assessed using magnetic resonance imaging (MRI), was associated with outcomes of IVF/ICSI-ET cycles.

Methods: This multicentre, joint, retrospective cohort study analysed the medical records of 67 infertile patients with adenomyosis who underwent IVF/ICSI with fresh and frozen-thawed ET at five participating facilities from January 2012 to December 2016 and for whom MRI data were available. Fifteen patients were excluded; therefore, the MRI data of 52 patients were evaluated by two radiologists. We assessed the localisation of and classified adenomyotic lesions into advanced (invades the full thickness of the uterine myometrium), extrinsic (localised on the serosal side), and intrinsic (localised on the endometrial side) subtypes.

Results: There were 40 advanced, nine extrinsic, and three intrinsic cases, and the outcomes of 100, 27, and nine ET cycles, respectively, were analysed. Pregnancy loss/clinical pregnancy and live birth rates of the advanced, extrinsic, and intrinsic groups were 64 % (16/25) and 9 % (9/100), 33.3 % (3/9) and 22.2 % (6/27), and 50 % (1/2) and 11.1 % (1/9), respectively. A logistic regression analysis adjusted for age, prior miscarriage, and body mass index showed that the extrinsic group had fewer pregnancy losses (odds ratio 0.06; 95 % confidence interval [CI]: 0.00-0.54, p = 0.026) and more live births (odds ratio 6.05; 95 % CI: 1.41-29.65, p = 0.018) than the advanced group.

Conclusions: Adenomyotic lesions exert different effects on IVF/ICSI-ET outcomes. Thus, MRI assessments of adenomyosis in infertile patients are beneficial. Establishment of treatment plans based on adenomyotic lesion localisation should be considered.
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http://dx.doi.org/10.1186/s12958-021-00764-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176737PMC
June 2021

Dynamics of Laterality in Relation to the Predator-Prey Interaction between the Piscivorous Chub "" and Its Prey "" in Lake Biwa.

Zoolog Sci 2021 Jun;38(3):231-237

Faculty of Engineering, Utsunomiya University, Utsunomiya, Tochigi 321-8585, Japan,

A Japanese piscivorous chub, "" (), and its main prey, "" (), both have laterally asymmetric bodies, similar to other fishes; each population consists of righty morphs and lefty morphs. This antisymmetric dimorphism has a genetic basis. Temporal changes in the ratios of laterality (i.e., frequency of righty morphs in a population) of these predator and prey fish species were investigated for a 20-year period at a pelagic site in the southwestern area of Lake Biwa, Japan. The dimorphism of each species was maintained dynamically throughout the period, and the ratio of laterality was found to change periodically in a semi-synchronized manner. Direct inspection of the relationship between the ratios of laterality of the two species indicated that the ratio of followed that of , suggesting that the predator-prey interaction was responsible for the semi-synchronized change. Stomach contents analysis of each revealed that cross-predation, in which righty predators catch lefty prey and lefty predators catch righty prey, occurred more frequently than the reverse combination (parallel-predation). This differential predation is presumed to cause frequency-dependent selection on the two morphs of the predator and prey, and to drive semi-synchronized changes in the laterality of the two species. Some discussion pertaining to the atypical form of the semi-synchronized change in laterality found in this study is presented from the viewpoint of predator-prey interaction in fishes.
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http://dx.doi.org/10.2108/zs200155DOI Listing
June 2021

Integrated Analysis of Whole Genome and Epigenome Data Using Machine Learning Technology: Toward the Establishment of Precision Oncology.

Front Oncol 2021 12;11:666937. Epub 2021 May 12.

Cancer Translational Research Team, RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.

With the completion of the International Human Genome Project, we have entered what is known as the post-genome era, and efforts to apply genomic information to medicine have become more active. In particular, with the announcement of the Precision Medicine Initiative by U.S. President Barack Obama in his State of the Union address at the beginning of 2015, "precision medicine," which aims to divide patients and potential patients into subgroups with respect to disease susceptibility, has become the focus of worldwide attention. The field of oncology is also actively adopting the precision oncology approach, which is based on molecular profiling, such as genomic information, to select the appropriate treatment. However, the current precision oncology is dominated by a method called targeted-gene panel (TGP), which uses next-generation sequencing (NGS) to analyze a limited number of specific cancer-related genes and suggest optimal treatments, but this method causes the problem that the number of patients who benefit from it is limited. In order to steadily develop precision oncology, it is necessary to integrate and analyze more detailed omics data, such as whole genome data and epigenome data. On the other hand, with the advancement of analysis technologies such as NGS, the amount of data obtained by omics analysis has become enormous, and artificial intelligence (AI) technologies, mainly machine learning (ML) technologies, are being actively used to make more efficient and accurate predictions. In this review, we will focus on whole genome sequencing (WGS) analysis and epigenome analysis, introduce the latest results of omics analysis using ML technologies for the development of precision oncology, and discuss the future prospects.
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http://dx.doi.org/10.3389/fonc.2021.666937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149908PMC
May 2021

A Novel Topical Fluorescent Probe for Detection of Glioblastoma.

Clin Cancer Res 2021 Jul 23;27(14):3936-3947. Epub 2021 May 23.

Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Purpose: Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma.

Experimental Design: We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover, and studies using U87 glioblastoma cell line were conducted to validate the findings.

Results: The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 ( to be responsible for cleaving the probe. was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells. assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues.

Conclusions: The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4518DOI Listing
July 2021

Radiation-free myeloablative conditioning consisting of fludarabine added to full-dose busulfan and cyclophosphamide in single-unit cord blood transplantation for adults.

Eur J Haematol 2021 May 24. Epub 2021 May 24.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

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http://dx.doi.org/10.1111/ejh.13669DOI Listing
May 2021

Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome in adolescent and young adult patients.

Bone Marrow Transplant 2021 May 15. Epub 2021 May 15.

Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable treatment option for adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS). The study aim was to evaluate epidemiological data and identify prognostic factors for AYA patients with MDS undergoing allogeneic HSCT. Here, 645 patients were selected from patients enrolled in a multicenter prospective registry for HSCT from 2000 to 2015. The primary endpoint was 3-year overall survival (OS). Survival rates were estimated using the Kaplan-Meier method. Prognostic factors were identified using the multivariable Cox proportional hazards model. The 3-year OS was 71.2% (95% confidence interval [CI]: 67.4-74.6%). In multivariable analysis, active disease status (adjusted hazard ratio: 1.54, 95% CI: 1.09-2.18, p = 0.016), poor cytogenetic risk (1.62, 1.12-2.36, p = 0.011), poor performance status (2.01, 1.13-3.56, p = 0.016), human leukocyte antigen (HLA)-matched unrelated donors (2.23, 1.39-3.59, p < 0.001), HLA-mismatched unrelated donors (2.16, 1.09-4.28, p = 0.027), and cord blood transplantation (2.44, 1.43-4.17, p = 0.001) were significantly associated with poor 3-year OS. In conclusion, in AYA patients with MDS the 3-year OS following allogeneic HSCT was 71.2%. Active disease status, poor cytogenetic risk, poor performance status, and donor sources other than related donors were associated with poor 3-year OS.
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http://dx.doi.org/10.1038/s41409-021-01324-8DOI Listing
May 2021

Exosome-derived miR-210 involved in resistance to osimertinib and epithelial-mesenchymal transition in EGFR mutant non-small cell lung cancer cells.

Thorac Cancer 2021 06 3;12(11):1690-1698. Epub 2021 May 3.

Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.

Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, the mechanisms of acquired drug resistance to osimertinib have not as yet been clarified. Exosomes and microRNAs (miRNAs) are involved in carcinogenesis and drug resistance in human cancers.

Methods: We used previously established osimertinib-resistant HCC827 (HCC827-OR) and PC-9 (PC-9-OR) cells. We evaluated the profiles of exosomal miRNA associated with resistance to osimertinib in EGFR-mutant NSCLC cells.

Results: Epithelial-mesenchymal transition (EMT) phenomenon was observed in HCC827-OR and PC-9-OR cells. Microarray and quantitative reverse transcription-polymerase chain reaction analysis revealed that miR-210-3p was co-upregulated in exosomes isolated from HCC827-OR and PC-9-OR cells compared with those isolated from parental HCC827 and PC-9 cells. HCC827-OR cell-derived exosomes induced EMT changes and resistance to osimertinib in HCC827 cells. Subsequently, the induction of miR-210-3p directly promoted the EMT phenomenon and resistance to osimertinib in HCC827 cells.

Conclusions: Exosomal miR-210-3p may play a crucial role in resistance to osimertinib in the tumor microenvironment of EGFR-mutant NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169289PMC
June 2021

Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Division of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.
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http://dx.doi.org/10.3390/ijms22084005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070547PMC
April 2021

A New Era of Neuro-Oncology Research Pioneered by Multi-Omics Analysis and Machine Learning.

Biomolecules 2021 04 12;11(4). Epub 2021 Apr 12.

Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo 104-0045, Japan.

Although the incidence of central nervous system (CNS) cancers is not high, it significantly reduces a patient's quality of life and results in high mortality rates. A low incidence also means a low number of cases, which in turn means a low amount of information. To compensate, researchers have tried to increase the amount of information available from a single test using high-throughput technologies. This approach, referred to as single-omics analysis, has only been partially successful as one type of data may not be able to appropriately describe all the characteristics of a tumor. It is presently unclear what type of data can describe a particular clinical situation. One way to solve this problem is to use multi-omics data. When using many types of data, a selected data type or a combination of them may effectively resolve a clinical question. Hence, we conducted a comprehensive survey of papers in the field of neuro-oncology that used multi-omics data for analysis and found that most of the papers utilized machine learning techniques. This fact shows that it is useful to utilize machine learning techniques in multi-omics analysis. In this review, we discuss the current status of multi-omics analysis in the field of neuro-oncology and the importance of using machine learning techniques.
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http://dx.doi.org/10.3390/biom11040565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070530PMC
April 2021

Early favipiravir treatment was associated with early defervescence in non-severe COVID-19 patients.

J Infect Chemother 2021 Jul 17;27(7):1051-1057. Epub 2021 Apr 17.

Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.

Introduction: The antiviral drug favipiravir has been shown to have in vitro antiviral activity against severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2). In this study, we investigated the clinical benefits and initiation of favipiravir treatment in patients with non-severe coronavirus-disease-2019 (COVID-19).

Methods: This study was a single-center retrospective cohort study. Receiver operating characteristic curves were drawn to calculate the area under the curve, and the optimal cut-off values for the time to initiate favipiravir treatment were calculated to predict defervescence within seven days. Univariate and multivariate Cox regression analyses were performed to identify potential influencing factors of defervescence. This was defined as a body temperature of less than 37 °C for at least 2 days.

Results: Data from 41 patients were used for the efficacy assessment. The days from the onset of fever to defervescence showed a positive correlation with the duration from the onset of fever to initiation of favipiravir treatment (r = 0.548, P < 0.001). The optimal cut-off value was the administration of favipiravir on day 4. Patients were assigned to two groups based on the optimal cut-off value from onset to initiation of favipiravir treatment: early treatment group (within 4-days) and late treatment group (more than 4-days). In the multivariate analysis, when adjusted for age, sex, and days from onset to initiation of favipiravir treatment, the significant factors were male sex and days of initiation of the favipiravir treatment.

Conclusions: We recommend that if favipiravir is to be used for treatment, it should be initiated as early as possible.
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http://dx.doi.org/10.1016/j.jiac.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052467PMC
July 2021

Cone-Beam Computed Tomography Fusion Technique for Vascular Assessment of Skull Base Meningiomas.

World Neurosurg 2021 Jul 24;151:61-69. Epub 2021 Apr 24.

Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.

Objective: Cone-beam computed tomography (CBCT) images for skull base tumors provide detailed vascular information and localization in regard to surrounding bony structures. We report use of the CBCT fusion technique for skull base meningiomas.

Methods: Six patients with petroclival or petrotentorial meningiomas supplied by multiple arterial systems were preoperatively evaluated using CBCT fusion imaging. Fusion images were reconstructed from three-dimensional rotational angiography with contrast agent injections from the internal carotid artery (ICA) and external carotid artery in 4 cases, vertebral artery and external carotid artery in 1 case, and ICA and vertebral artery in 1 case.

Results: The feeding pedicles and tumor stains from 2 arterial systems were differentiated by separate colors. The courses and territories of the ICA dural feeders or ICA/vertebral artery pial feeders were easily distinguished from the external carotid artery dural feeders. Anastomoses between thin feeders from different arterial systems could be detected. Mixed stain (stain with both colors) was observed in some tumor compartments, suggesting dual supply from 2 arterial systems and the presence of peritumoral anastomoses. All patients underwent preoperative embolization without complications.

Conclusions: CBCT fusion images clearly visualized the feeders from each arterial system, the vascular compartments within the tumor, and possible peritumoral anastomoses. This technique provides a substantial contribution to both preoperative embolization and surgical resection of skull base meningiomas.
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http://dx.doi.org/10.1016/j.wneu.2021.04.065DOI Listing
July 2021

Invasive pneumococcal disease affected the fatal outcome in a COVID-19 patient.

J Infect Chemother 2021 Jul 8;27(7):1108-1111. Epub 2021 Apr 8.

Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.

A 68-year-old man experienced fever and cough and was referred to a hospital for day 4. He had a positive reverse transcription-polymerase chain reaction result for severe acute respiratory syndrome coronavirus-2. On day 12, his PaO/FiO ratio worsened to 120 and he was transferred to Sapporo Medical University Hospital for treatment using extracorporeal membrane oxygenation. Venous blood cultures were positive for Streptococcus pneumoniae, which were serotype 3, mucoid-type, and penicillin susceptible. Coinfections with coronavirus disease-2019 and invasive pneumococcal disease are rare; however, they are associated with a higher case fatality than either of the conditions manifesting alone.
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http://dx.doi.org/10.1016/j.jiac.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026269PMC
July 2021

Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU).

J Infect Chemother 2021 Aug 27;27(8):1169-1180. Epub 2021 May 27.

Department of Urology, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, 125-8506, Japan; Japanese Research Group for Urinary Tract Infection (JRGU), 1-1 Mukogawa- Machi, Nishinomiya, 663-8501, Japan.

Introduction: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data.

Methods: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method.

Results: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to β-lactams including carbapenems was 40-60%.

Conclusions: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.
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http://dx.doi.org/10.1016/j.jiac.2021.03.012DOI Listing
August 2021

Importance of experienced thermal history: Effect of acclimation temperatures on the high-temperature tolerance and growth performance of juvenile marbled flounder.

J Therm Biol 2021 Apr 6;97:102831. Epub 2021 Jan 6.

Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan. Electronic address:

Experienced thermal history often affects the temperature tolerance of fish; however, the effect of thermal history on growth performance is unclear. To contribute to effective stocking (release of hatchery-reared juveniles in the field), we conducted four laboratory experiments using juvenile marbled flounder (Pseudopleuronectes yokohamae, around 30 mm standard length and 0.3 g body wet weight) acclimated at 12 °C and 24 °C for approximately 2 weeks to investigate the effects of acclimation temperature on high-temperature tolerance, food consumption, and growth performance. The acclimation to 24 °C increased tolerance to high temperatures, as shown in a 24-h exposure experiment and in a temperature elevation experiment. The 50% lethal temperature (upper incipient lethal temperature) was estimated to be 25.9 °C and 29.0 °C for the 12 °C and 24 °C acclimation groups, respectively. In subsequent experiments, we tested the effects of high and low temperature acclimation on the food consumption and growth performance of two size groups of juveniles (28.7 ± 2.0 and 34.5 ± 2.9 mm, mean ± SD), that were reared at temperatures ranging from 14 °C to 23 °C. The optimal temperature for growth was 20 °C and did not differ between the acclimation temperatures or between the size groups. However, food consumption and growth performance were suppressed by acute temperature changes. Specifically, feeding and growth were lower in the 24 °C-acclimated group than in the 12 °C-acclimated group when exposed to 14 °C, which is close to the natural water temperature at release in the field. These results suggest that experienced thermal history does not affect the optimal temperature but can affect the growth performance of juveniles. To maximize the post-release growth of hatchery-reared juveniles, the influence of thermal history should be taken into consideration and acute thermal changes before release should be avoided.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102831DOI Listing
April 2021

Early-Phase Peripheral Blood Eosinophilia Predicts Lower Overall and Non-Relapse Mortality After Single-Unit Cord Blood Transplantation.

Transplant Cell Ther 2021 04 4;27(4):336.e1-336.e9. Epub 2021 Feb 4.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Peripheral blood eosinophilia has been associated with the development of graft-versus-host disease (GVHD) and survival after allogeneic hematopoietic cell transplantation (HCT). However, the impacts of eosinophilia on cord blood transplantation (CBT) outcomes remain unclear. The objective of this study was to examine the associations between eosinophilia and overall survival, relapse incidence, non-relapse mortality, and acute and chronic GVHD after single-unit CBT for adults. We retrospectively analyzed the data for 225 adult patients who received single-unit CBT at our institute between March 2004 and March 2020. The cumulative incidence of eosinophilia, defined as an absolute eosinophil count of ≥500 × 10/L in peripheral blood, was 48.9% (95% confidence interval, 42.2% to 55.2%) at 60 days after CBT. Recipient cytomegalovirus seronegative status and higher cryopreserved cord blood CD34 cell dose were significantly associated with a higher incidence of eosinophilia after CBT. Among patients who achieved neutrophil recovery, neutrophil recovery was significantly earlier in patient with eosinophilia compared to those without eosinophilia (P = .016). Serum levels of interleukin-5 at 4 weeks were significantly higher in patients with eosinophilia compared with those without eosinophilia (P = .041). Multivariate analysis, in which the development of eosinophilia was treated as a time-dependent covariate, showed that eosinophilia was significantly associated with lower overall mortality (hazard ratio [HR], .58; P = .034) and non-relapse mortality (HR, .41; P = .029), but not relapse incidence or development of acute or chronic GVHD. Our data suggested that early-phase eosinophilia is a predictor of favorable outcomes in adult patients undergoing single-unit CBT.
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http://dx.doi.org/10.1016/j.jtct.2021.01.027DOI Listing
April 2021

Prognostic Impact of the Fractionation of Total Body Irradiation for Patients with Acute Myeloid Leukemia Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 02 13;27(2):185.e1-185.e6. Epub 2020 Dec 13.

Aichi Cancer Center, Nagoya, Japan. Electronic address:

Fractionated total body irradiation (TBI) at a total dose of 12 Gy is widely used for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT); however, there is limited information regarding the optimal number of fractions. To address this issue, Japanese nationwide transplantation registry data were analyzed. Because it was found that TBI was delivered almost exclusively in 4 (n = 1215, 30%) or 6 fractions (n = 2697, 67%), we focused on comparing 4- versus 6-fraction TBI. Compared to 6-fraction TBI, the 4-fraction version was associated with reduced risk of overall mortality (P = .002) and relapse (P = .018), while there was no difference in the risk of nonrelapse mortality (P = .422). The 4-fraction version did not aggravate acute graft-versus-host disease (GVHD), interstitial pneumonia, or sinusoidal obstruction syndrome of the liver. Chronic GVHD developed more frequently with the use of 4-fraction TBI, although the incidence of extensive chronic GVHD was similar. Subgroup analyses revealed that the 4-fraction version provided benefits for patients in non-complete remission (non-CR) but not for those in CR at transplantation. These findings suggest the advantage of 4-fraction over 6-fraction TBI for patients with AML undergoing allogeneic HCT in non-CR.
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http://dx.doi.org/10.1016/j.jtct.2020.10.018DOI Listing
February 2021

Evaluation of two commercial molecular diagnostic assays: The Xpert Norovirus and the TRCReady NV.

J Infect Chemother 2021 Jul 1;27(7):1115-1118. Epub 2021 Apr 1.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Introduction: Norovirus is highly contagious, and a few particles of this virus are sufficient to make people sick. It is desirable to develop quick and accurate laboratory methods to detect norovirus.

Methods: We evaluated two commercial molecular diagnostic assays, the Xpert Norovirus and the TRCReady NV, using clinical fecal samples. A reference method was performed using in-house real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR).

Results: The results of the real-time RT-PCR analysis of 60 suspected cases of norovirus infection showed 5 cases of Genogroup I (GI) positives and 21 cases of GII positives, among which was 1 GI and GII coinfection. The viral titers of the norovirus-positive samples ranged from 1.54 × 10 to 3.14 × 10 copies/μL. Norovirus GII.17 (12 cases, 48%) was the most frequently detected genotype in this study, followed by GII.4 (6 cases, 24%), GII.13 (2 cases, 8%), GI.2 (2 cases, 8%), GI.3 (2 cases, 8%), GI.1 (1 case, 4%), and GII.2 (1 case, 4%). The kappa coefficient was 1.000 (95% CI: 1.000-1.000) for Xpert Norovirus and 0.966 (95% CI: 0.896-1.000) for TRCReady NV, indicating a strong agreement.

Conclusions: Norovirus detection using Xpert Norovirus and TRCReady NV is highly useful for diagnosis and infection control because these assays are easy to operate, quick, and exhibit almost the same performance as that of real-time RT-PCR.
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http://dx.doi.org/10.1016/j.jiac.2021.02.004DOI Listing
July 2021

Fine-Tuning Approach for Segmentation of Gliomas in Brain Magnetic Resonance Images with a Machine Learning Method to Normalize Image Differences among Facilities.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Division of Molecular Modification and Cancer Biology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Machine learning models for automated magnetic resonance image segmentation may be useful in aiding glioma detection. However, the image differences among facilities cause performance degradation and impede detection. This study proposes a method to solve this issue. We used the data from the Multimodal Brain Tumor Image Segmentation Benchmark (BraTS) and the Japanese cohort (JC) datasets. Three models for tumor segmentation are developed. In our methodology, the BraTS and JC models are trained on the BraTS and JC datasets, respectively, whereas the fine-tuning models are developed from the BraTS model and fine-tuned using the JC dataset. Our results show that the Dice coefficient score of the JC model for the test portion of the JC dataset was 0.779 ± 0.137, whereas that of the BraTS model was lower (0.717 ± 0.207). The mean Dice coefficient score of the fine-tuning model was 0.769 ± 0.138. There was a significant difference between the BraTS and JC models ( < 0.0001) and the BraTS and fine-tuning models ( = 0.002); however, no significant difference between the JC and fine-tuning models ( = 0.673). As our fine-tuning method requires fewer than 20 cases, this method is useful even in a facility where the number of glioma cases is small.
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http://dx.doi.org/10.3390/cancers13061415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003655PMC
March 2021