This clinical image presents a report on the diagnosis and treatment of anti‐NMDAR encephalitis, ... more This clinical image presents a report on the diagnosis and treatment of anti‐NMDAR encephalitis, a rare disease. This report emphasizes the importance of a differential diagnosis for acute psychiatric symptoms. Accurate and timely diagnosis is critical for the selection and implementation of treatment and for optimal patient outcomes.
Background: The introduction of rituximab into the therapy of DLBCL has improved the prognosis dr... more Background: The introduction of rituximab into the therapy of DLBCL has improved the prognosis dramatically. However, relapse in CNS is still the issue. We studied the prognosis and risk factors of CNS recurrence in DLBCL. Method: Between Jan. 1996 and Apr. 2007, 441 patients were diagnosed to have DLBCL in our institute, of whom 31 patients were excluded due to CNS involvement at the time of initial diagnosis. We have analyzed 410 cases, in which 37 cases had relapsed in CNS. Before Sep. 2003, 168 patients were treated with the regimen based on CHOP, and after Sep. 2003, 242 patients were treated with the regimen based on CHOP plus rituximab. Once relapsing in CNS, the patients were treated with systemic chemotherapy plus high-dose methotrexate or radiation with intrathecal methotrexate. The risk category by the international prognostic index of these 411 cases was assessed as low: 36%, low-intermediate: 15%, high-intermediate: 23%, and high: 26%. Results: The median age was 71 years old (range: 17–92). Median follow-up period was 507 days, and the median period free from relapsing in CNS was 331 days. The mean survival period of the cases with CNS relapse, of the cases relapsed outside the CNS, and of the non-relapsed cases was 1328 days, 2290 days, and 2817days, respectively. The overall survival rate of cases with CNS relapse was significantly lower than that of the cases relapsed outside the CNS, or than that of the non-relapsed cases (p=0.0233, p=0.0003, respectively). Multivariate Cox regression analysis identified the increased lactate dehydrogenase (p=0.014), the involvement of more than one extranodal site (p=0.006), and not using rituximab before CNS relapse (p=0.040) as an independent predictor of CNS recurrence. Conclusion: CNS relapse has extremely poor prognosis than relapse outside the CNS in DLBCL. Rituximab may be effective in preventing CNS relapse. Since rituximab poorly penetrates into CNS, this may partly due to the reduction of all recurrence by rituximab. According to the risk assessment in CNS relapse, an effective CNS prophylaxis strategy should be determined.
Grid square statistics – a kind of spatial statistics – is useful for compiling, disseminating, a... more Grid square statistics – a kind of spatial statistics – is useful for compiling, disseminating, and analyzing statistics regarding anonymization. We recently proposed a natural extension of the Japanese Industrial Standards for grid square code (JIS X0410) for use worldwide. The grid square approach can produce numerous types of statistics associated with any geographic location in the world, identify any type of grid square statistics, and analyze relationships among various types of grid square statistics. This paper proposes a World Grid Square data reference architecture to manage World Grid Square statistics in a big data analytics platform following the Big Data Reference Architecture. We identify data sources such as government statistics, satellite imagery, and point data from internet providers and show how to transform World Grid Square statistics and data from grid data, point data, and polygon data. We further propose a system for providing grid square statistics in a number of context-specific areas and demonstrate their application in a data visualization and analytics platform.
This paper analyzes Grid Square Statistics on job opportunity ads collected from a Japanese Inter... more This paper analyzes Grid Square Statistics on job opportunity ads collected from a Japanese Internet job matching site (“from A navi”). We confirm a relationship between the number of job opportunities and socioeconomic quantities (the population, the numbers of firms and workers) in each 1-km and 10-km Grid Square. The number of workers is the best variable to explain the number of job opportunities out of the three candidates of socioeconomic quantities in the 1-km Grid Squares, however explanatory powers of three socioeconomic quantities to the number of job opportunities are just slightly different from one another in the 10-km Grid Squares depending on observation dates. We propose that the power law exponent estimated from the daily cross-sectional relationship can be used as the production ratio of job opportunities to socioeconomic quantities. It is determined that the production ratios vary in time and show seasonality associated with the Japanese calendar. Moreover, we compute 1-km Grid Square Statistics about job opportunity data based on JIS X0410 and we clarify relationships between the number of job opportunities and the number of occupation types. We extracted industrial clusters in terms of job opportunities and the types of job occupations in Japan.
ABSTRACT This article considers the relationship between the price of flight tickets and their ge... more ABSTRACT This article considers the relationship between the price of flight tickets and their geodesic distance from the departure airport to the destination. Using the data collected from a Japanese flight booking site, I empirically investigated demand-supply situations from parameter estimates of an nth order polynomial function of the price in terms of the distance on each observation date. An adequate order of the polynomial function is determined by using two kinds of information criterions (AIC and BIC). It is confirmed that the ticket availability strongly depends on the Japanese calendar date and that the parameter estimates also depend on the calendar date. The parameter estimates may correspond to demand-supply situations of the Japanese air travel market.
Abemaciclib, a selective cyclin dependent kinases 4 and 6(CDK4 & 6)inhibitor, is under developmen... more Abemaciclib, a selective cyclin dependent kinases 4 and 6(CDK4 & 6)inhibitor, is under development for the treatment of hormone receptor(HR)-positive, HER2-negative breast cancer. CDK4 & 6 inhibitors attenuate Rb phosphorylation resulting in a G1 arrest and tumor growth inhibition. Abemaciclib potently inhibits both CDK4 and CDK6, with 14-fold higher potency for CDK4-cyclin D1 complexes than CDK6-cyclin D3 in enzymatic assays. Low frequency of severe neutropenia requiring drug holiday in clinical trials of abemaciclib in breast cancer patients enables continuous daily dosing. Abemaciclib's preclinical difference in selectivity for CDK4 vs CDK6 could help explain its safety profile and ability to be dosed on a continuous schedule. Continuous inhibition of CDK4 & 6 by abemaciclib results in irreversible growth inhibition through induction of senescence and apoptosis in breast cancer cell lines. Abemaciclib shows its growth inhibitory effect particularly in estrogen receptor(ER)- positive breast cancer, and sensitivity to abemaciclib is associated with high ER levels and Rb positivity. In animals bearing ERpositive breast cancer, significant tumor growth inhibition was shown by single-agent and combination with anti-estrogen agents. Abemaciclib penetrates the blood-brain barrier and showed antitumor activity in glioma models. As described above, there are some characteristics demonstrate differences of abemaciclib and other CDK4 & 6 inhibitors. In clinical studies, abemaciclib has demonstrated efficacy and generally tolerable safety profile in HR-positive, HER2-negative breast cancer patients.
Background: Although umbilical cord blood has been used successfully as an alternative donor sour... more Background: Although umbilical cord blood has been used successfully as an alternative donor source to treat hematological disorders, cord blood transplantation (CBT) is frequently complicated by graft failure and relapse of original diseases. Since recipient-derived hematopoietic cells persist or increase under these reasons, analysis of donor-recipient mixed chimerism (MC) might be useful for their diagnosis. Objective: Since most CBT involves human leukocyte antigen (HLA)-mismatched transplantation especially for adult patients, we have developed a flow cytometry-based method of MC analysis using anti-HLA antibodies (HLA-FACS method) to detect mismatched antigens. Patients and methods: We analyzed MC in 14 patients after CBT using HLA-FACS method including 9 cases with weekly analysis using peripheral blood in first 4 weeks for monitoring of the engraftment and 9 cases with serial analysis using bone marrow samples for detection of the minimal residual disease (MRD). Results 1 (monitoring of engraftment): In our first patient with acute myelogenous leukemia (AML), MC in peripheral blood could be detected at week 1 after CBT; the recipient-derived cells were mainly observed in the CD4+ T-cell subset. Recipient-derived cells gradually decreased and completely disappeared at week 4 after CBT. In our second patient with myelodysplastic syndrome, recipient-derived cells decreased to 1.5% of mononuclear cells at week 2 after CBT, then started to increase at week 3 and persisted with the frequency of around 10% by week 6. MC was mainly caused by recipient-derived monocytes in this patient. After tapering of cyclosporine A, a rapid decrease of recipient-derived cells was observed from week 6 to week 10. Another 7 patients showed complete donor chimerism at week 3 after transplant. Result 2 (monitoring of MRD): In the first case, the percentage of recipient-derived cells among the CD34+CD45dim fraction in bone marrow was 0.2% on day 159. On day 281, however, these cells significantly increased to 5.7%. To elucidate whether the recipient-derived CD34+CD45dim cells were leukemia cells or not, we separately sorted donor- and recipient-derived CD34+CD45dim cells and analyzed the leukemia-specific AML1/ETO chimeric genes by the fluorescent in situ hybridization method. Recipient-derived CD34+CD45dim cells but not donor-derived ones were positive for AML1/ETO fusion signals. We have detected significant frequency of recipient cells in the CD34+CD45dim fraction of bone marrow in the other patient followed by clinical diagnosis of leukemia relapse at 3 weeks later. No sign of recipient recurrence was observed in other 7 patients. Conclusion: These results provided a proof of concept for an approach that may have utility in the early diagnosis of graft failure and relapse of leukemia by the HLA-FACS method for patients received HLA-mismatched CBT.
A 70-year-old woman under anticonvulsive therapy with carbamazepine and valproate was diagnosed a... more A 70-year-old woman under anticonvulsive therapy with carbamazepine and valproate was diagnosed as polymyalgia rheumatica. She responded to the prednisolone therapy so poorly that she required high dose prednisolone and methotrexate, and it was difficult to reduce prednisolone. After discontinuing of carbamazepine, her steroid response improved immediately. Carbamazepine is known to induce hepatic enzyme CYP3A4 and alter metabolism of other drugs. In our case, the effect of prednisolone might have been reduced by carbamazepine. This case suggests more attention should be paid to the interaction between carbamazepine and prednisolone.
This clinical image presents a report on the diagnosis and treatment of anti‐NMDAR encephalitis, ... more This clinical image presents a report on the diagnosis and treatment of anti‐NMDAR encephalitis, a rare disease. This report emphasizes the importance of a differential diagnosis for acute psychiatric symptoms. Accurate and timely diagnosis is critical for the selection and implementation of treatment and for optimal patient outcomes.
Background: The introduction of rituximab into the therapy of DLBCL has improved the prognosis dr... more Background: The introduction of rituximab into the therapy of DLBCL has improved the prognosis dramatically. However, relapse in CNS is still the issue. We studied the prognosis and risk factors of CNS recurrence in DLBCL. Method: Between Jan. 1996 and Apr. 2007, 441 patients were diagnosed to have DLBCL in our institute, of whom 31 patients were excluded due to CNS involvement at the time of initial diagnosis. We have analyzed 410 cases, in which 37 cases had relapsed in CNS. Before Sep. 2003, 168 patients were treated with the regimen based on CHOP, and after Sep. 2003, 242 patients were treated with the regimen based on CHOP plus rituximab. Once relapsing in CNS, the patients were treated with systemic chemotherapy plus high-dose methotrexate or radiation with intrathecal methotrexate. The risk category by the international prognostic index of these 411 cases was assessed as low: 36%, low-intermediate: 15%, high-intermediate: 23%, and high: 26%. Results: The median age was 71 years old (range: 17–92). Median follow-up period was 507 days, and the median period free from relapsing in CNS was 331 days. The mean survival period of the cases with CNS relapse, of the cases relapsed outside the CNS, and of the non-relapsed cases was 1328 days, 2290 days, and 2817days, respectively. The overall survival rate of cases with CNS relapse was significantly lower than that of the cases relapsed outside the CNS, or than that of the non-relapsed cases (p=0.0233, p=0.0003, respectively). Multivariate Cox regression analysis identified the increased lactate dehydrogenase (p=0.014), the involvement of more than one extranodal site (p=0.006), and not using rituximab before CNS relapse (p=0.040) as an independent predictor of CNS recurrence. Conclusion: CNS relapse has extremely poor prognosis than relapse outside the CNS in DLBCL. Rituximab may be effective in preventing CNS relapse. Since rituximab poorly penetrates into CNS, this may partly due to the reduction of all recurrence by rituximab. According to the risk assessment in CNS relapse, an effective CNS prophylaxis strategy should be determined.
Grid square statistics – a kind of spatial statistics – is useful for compiling, disseminating, a... more Grid square statistics – a kind of spatial statistics – is useful for compiling, disseminating, and analyzing statistics regarding anonymization. We recently proposed a natural extension of the Japanese Industrial Standards for grid square code (JIS X0410) for use worldwide. The grid square approach can produce numerous types of statistics associated with any geographic location in the world, identify any type of grid square statistics, and analyze relationships among various types of grid square statistics. This paper proposes a World Grid Square data reference architecture to manage World Grid Square statistics in a big data analytics platform following the Big Data Reference Architecture. We identify data sources such as government statistics, satellite imagery, and point data from internet providers and show how to transform World Grid Square statistics and data from grid data, point data, and polygon data. We further propose a system for providing grid square statistics in a number of context-specific areas and demonstrate their application in a data visualization and analytics platform.
This paper analyzes Grid Square Statistics on job opportunity ads collected from a Japanese Inter... more This paper analyzes Grid Square Statistics on job opportunity ads collected from a Japanese Internet job matching site (“from A navi”). We confirm a relationship between the number of job opportunities and socioeconomic quantities (the population, the numbers of firms and workers) in each 1-km and 10-km Grid Square. The number of workers is the best variable to explain the number of job opportunities out of the three candidates of socioeconomic quantities in the 1-km Grid Squares, however explanatory powers of three socioeconomic quantities to the number of job opportunities are just slightly different from one another in the 10-km Grid Squares depending on observation dates. We propose that the power law exponent estimated from the daily cross-sectional relationship can be used as the production ratio of job opportunities to socioeconomic quantities. It is determined that the production ratios vary in time and show seasonality associated with the Japanese calendar. Moreover, we compute 1-km Grid Square Statistics about job opportunity data based on JIS X0410 and we clarify relationships between the number of job opportunities and the number of occupation types. We extracted industrial clusters in terms of job opportunities and the types of job occupations in Japan.
ABSTRACT This article considers the relationship between the price of flight tickets and their ge... more ABSTRACT This article considers the relationship between the price of flight tickets and their geodesic distance from the departure airport to the destination. Using the data collected from a Japanese flight booking site, I empirically investigated demand-supply situations from parameter estimates of an nth order polynomial function of the price in terms of the distance on each observation date. An adequate order of the polynomial function is determined by using two kinds of information criterions (AIC and BIC). It is confirmed that the ticket availability strongly depends on the Japanese calendar date and that the parameter estimates also depend on the calendar date. The parameter estimates may correspond to demand-supply situations of the Japanese air travel market.
Abemaciclib, a selective cyclin dependent kinases 4 and 6(CDK4 & 6)inhibitor, is under developmen... more Abemaciclib, a selective cyclin dependent kinases 4 and 6(CDK4 & 6)inhibitor, is under development for the treatment of hormone receptor(HR)-positive, HER2-negative breast cancer. CDK4 & 6 inhibitors attenuate Rb phosphorylation resulting in a G1 arrest and tumor growth inhibition. Abemaciclib potently inhibits both CDK4 and CDK6, with 14-fold higher potency for CDK4-cyclin D1 complexes than CDK6-cyclin D3 in enzymatic assays. Low frequency of severe neutropenia requiring drug holiday in clinical trials of abemaciclib in breast cancer patients enables continuous daily dosing. Abemaciclib's preclinical difference in selectivity for CDK4 vs CDK6 could help explain its safety profile and ability to be dosed on a continuous schedule. Continuous inhibition of CDK4 & 6 by abemaciclib results in irreversible growth inhibition through induction of senescence and apoptosis in breast cancer cell lines. Abemaciclib shows its growth inhibitory effect particularly in estrogen receptor(ER)- positive breast cancer, and sensitivity to abemaciclib is associated with high ER levels and Rb positivity. In animals bearing ERpositive breast cancer, significant tumor growth inhibition was shown by single-agent and combination with anti-estrogen agents. Abemaciclib penetrates the blood-brain barrier and showed antitumor activity in glioma models. As described above, there are some characteristics demonstrate differences of abemaciclib and other CDK4 & 6 inhibitors. In clinical studies, abemaciclib has demonstrated efficacy and generally tolerable safety profile in HR-positive, HER2-negative breast cancer patients.
Background: Although umbilical cord blood has been used successfully as an alternative donor sour... more Background: Although umbilical cord blood has been used successfully as an alternative donor source to treat hematological disorders, cord blood transplantation (CBT) is frequently complicated by graft failure and relapse of original diseases. Since recipient-derived hematopoietic cells persist or increase under these reasons, analysis of donor-recipient mixed chimerism (MC) might be useful for their diagnosis. Objective: Since most CBT involves human leukocyte antigen (HLA)-mismatched transplantation especially for adult patients, we have developed a flow cytometry-based method of MC analysis using anti-HLA antibodies (HLA-FACS method) to detect mismatched antigens. Patients and methods: We analyzed MC in 14 patients after CBT using HLA-FACS method including 9 cases with weekly analysis using peripheral blood in first 4 weeks for monitoring of the engraftment and 9 cases with serial analysis using bone marrow samples for detection of the minimal residual disease (MRD). Results 1 (monitoring of engraftment): In our first patient with acute myelogenous leukemia (AML), MC in peripheral blood could be detected at week 1 after CBT; the recipient-derived cells were mainly observed in the CD4+ T-cell subset. Recipient-derived cells gradually decreased and completely disappeared at week 4 after CBT. In our second patient with myelodysplastic syndrome, recipient-derived cells decreased to 1.5% of mononuclear cells at week 2 after CBT, then started to increase at week 3 and persisted with the frequency of around 10% by week 6. MC was mainly caused by recipient-derived monocytes in this patient. After tapering of cyclosporine A, a rapid decrease of recipient-derived cells was observed from week 6 to week 10. Another 7 patients showed complete donor chimerism at week 3 after transplant. Result 2 (monitoring of MRD): In the first case, the percentage of recipient-derived cells among the CD34+CD45dim fraction in bone marrow was 0.2% on day 159. On day 281, however, these cells significantly increased to 5.7%. To elucidate whether the recipient-derived CD34+CD45dim cells were leukemia cells or not, we separately sorted donor- and recipient-derived CD34+CD45dim cells and analyzed the leukemia-specific AML1/ETO chimeric genes by the fluorescent in situ hybridization method. Recipient-derived CD34+CD45dim cells but not donor-derived ones were positive for AML1/ETO fusion signals. We have detected significant frequency of recipient cells in the CD34+CD45dim fraction of bone marrow in the other patient followed by clinical diagnosis of leukemia relapse at 3 weeks later. No sign of recipient recurrence was observed in other 7 patients. Conclusion: These results provided a proof of concept for an approach that may have utility in the early diagnosis of graft failure and relapse of leukemia by the HLA-FACS method for patients received HLA-mismatched CBT.
A 70-year-old woman under anticonvulsive therapy with carbamazepine and valproate was diagnosed a... more A 70-year-old woman under anticonvulsive therapy with carbamazepine and valproate was diagnosed as polymyalgia rheumatica. She responded to the prednisolone therapy so poorly that she required high dose prednisolone and methotrexate, and it was difficult to reduce prednisolone. After discontinuing of carbamazepine, her steroid response improved immediately. Carbamazepine is known to induce hepatic enzyme CYP3A4 and alter metabolism of other drugs. In our case, the effect of prednisolone might have been reduced by carbamazepine. This case suggests more attention should be paid to the interaction between carbamazepine and prednisolone.
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Papers by Aki Sato