新規ビスホスフォネート製剤 disodium dihydrogen-4-[(methylthio) phenylthio] methanebisphosphonate(MPMBP)の局所投与による Wistarラット大腿骨欠損治癒に対する効果

要約のみTohoku University高橋哲課

High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes

博士（医学）福島県立医科大

Policy-Adaptive Estimator Selection for Off-Policy Evaluation

Off-policy evaluation (OPE) aims to accurately evaluate the performance of counterfactual policies using only offline logged data. Although many estimators have been developed, there is no single estimator that dominates the others, because the estimators' accuracy can vary greatly depending on a given OPE task such as the evaluation policy, number of actions, and noise level. Thus, the data-driven estimator selection problem is becoming increasingly important and can have a significant impact on the accuracy of OPE. However, identifying the most accurate estimator using only the logged data is quite challenging because the ground-truth estimation accuracy of estimators is generally unavailable. This paper studies this challenging problem of estimator selection for OPE for the first time. In particular, we enable an estimator selection that is adaptive to a given OPE task, by appropriately subsampling available logged data and constructing pseudo policies useful for the underlying estimator selection task. Comprehensive experiments on both synthetic and real-world company data demonstrate that the proposed procedure substantially improves the estimator selection compared to a non-adaptive heuristic.Comment: accepted at AAAI'2

Off-Policy Evaluation of Ranking Policies under Diverse User Behavior

Ranking interfaces are everywhere in online platforms. There is thus an ever growing interest in their Off-Policy Evaluation (OPE), aiming towards an accurate performance evaluation of ranking policies using logged data. A de-facto approach for OPE is Inverse Propensity Scoring (IPS), which provides an unbiased and consistent value estimate. However, it becomes extremely inaccurate in the ranking setup due to its high variance under large action spaces. To deal with this problem, previous studies assume either independent or cascade user behavior, resulting in some ranking versions of IPS. While these estimators are somewhat effective in reducing the variance, all existing estimators apply a single universal assumption to every user, causing excessive bias and variance. Therefore, this work explores a far more general formulation where user behavior is diverse and can vary depending on the user context. We show that the resulting estimator, which we call Adaptive IPS (AIPS), can be unbiased under any complex user behavior. Moreover, AIPS achieves the minimum variance among all unbiased estimators based on IPS. We further develop a procedure to identify the appropriate user behavior model to minimize the mean squared error (MSE) of AIPS in a data-driven fashion. Extensive experiments demonstrate that the empirical accuracy improvement can be significant, enabling effective OPE of ranking systems even under diverse user behavior.Comment: KDD2023 Research trac

In Vitro and In Vivo Evaluation of Starfish Bone-Derived -Tricalcium Phosphate as a Bone Substitute Material

We evaluated starfish-derived -tricalcium phosphate (Sf-TCP) obtained by phosphatization of starfish-bone-derived porous calcium carbonate as a potential bone substitute material. The Sf-TCP had a communicating pore structure with a pore size of approximately 10 m. Although the porosity of Sf-TCP was similar to that of Cerasorb M (CM)a commercially available -TCP bone fillerthe specific surface area was roughly three times larger than that of CM. Observation by scanning electron microscopy showed that pores communicated to the inside of the Sf-TCP. Cell growth tests showed that Sf-TCP improved cell proliferation compared with CM. Cells grown on Sf-TCP showed stretched filopodia and adhered; cells migrated both to the surface and into pores. In vivo, vigorous tissue invasion into pores was observed in Sf-TCP, and more fibrous tissue was observed for Sf-TCP than CM. Moreover, capillary formation into pores was observed for Sf-TCP. Thus, Sf-TCP showed excellent biocompatibility in vitro and more vigorous bone formation in vivo, indicating the possible applications of this material as a bone substitute. In addition, our findings suggested that mimicking the microstructure derived from whole organisms may facilitate the development of superior artificial bone.ArticleMATERIALS. 12(11):1881 (2019)journal articl

Evaluation of MC3T3-E1 Cell Osteogenesis in Different Cell Culture Media

Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials.ArticleInternational Journal of Molecular Sciences. 22(14):7752 (2021)journal articl

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.ArticleNANOMATERIALS. 10(7):1374 (2020)journal articl

Genotype prevalence and age distribution of human papillomavirus from infection to cervical cancer in Japanese women: A systematic review and meta-analysis

Background: National HPV vaccination coverage in Japan is less than one percent of the eligible population and cervical cancer incidence and mortality are increasing. This systematic review and meta-analysis aimed to provide a comprehensive estimate of HPV genotype prevalence for Japan. Methods: English and Japanese databases were searched to March 2021 for research reporting HPV genotypes in cytology and histology samples from Japanese women. Summary estimates were calculated by disease stage from cytology only assessment – Normal, ASCUS, LSIL, HSIL and from histological assessment – CIN1, CIN2, CIN3/AIS, ICC (ICC-SCC, and ICC-ADC), and other. A random-effects meta–analysis was used to calculate summary prevalence estimates of any-HPV, high-risk (HR) and low-risk (LR) vaccine types, and vaccine genotypes (bivalent, quadrivalent, or nonavalent). This study was registered with PROSPERO: CRD42018117596. Results: A total of 57759 women with normal cytology, 1766 ASCUS, 3764 LSIL, 2017 HSIL, 3130 CIN1, 1219 CIN2, 869 CIN3/AIS, and 4306 ICC (which included 1032 ICC-SCC, and 638 ICC-ADC) were tested for HPV. The summary estimate of any-HPV genotype in women with normal cytology was 15·6% (95% CI: 12·3–19·4) and in invasive cervical cancer (ICC) was 85·6% (80·7–89·8). The prevalence of HR-HPV was 86·0% (95% CI: 73·9–94·9) for cytological cases of HSIL, 76·9% (52·1–94·7) for histological cases of CIN3/AIS, and 75·7% (68·0–82·6) for ICC. In women with ICC, the summary prevalence of bivalent vaccine genotypes was 58·5% (95% CI: 52·1–64·9), for quadrivalent genotypes was 58·6% (52·2–64·9) and for nonavalent genotypes was 71·5% (64·9–77·6), and of ICC cases that were HPV positive over 90% of infections are nonavalent vaccine preventable. There was considerable heterogeneity in all HPV summary estimates and for ICC, this heterogeneity was not explained by variability in study design, sample type, HPV assay type, or HPV DNA detection method, although studies published in the 1990s had lower prevalence estimates of any-HPV and HR HPV genotypes. Interpretations: HPV prevalence is high among Japanese women. The nonavalent vaccine is likely to have the greatest impact on reducing cervical cancer incidence and mortality in Japan

Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT) : a multicenter, randomized, open-label, parallel-group study

Introduction: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). Research design and methods: Changes in mean daily blood glucose level before and after 48–72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. Results: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183–156mg/dL, p=0.001), maximum glucose (300–253, p<0.01), and SD glucose (57–45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2’-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. Conclusions: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48–72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in ‘time in ranges’ and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies

Silverrush. Xii. Intensity Mapping for Ly Α Emission Extending over 100-1000 Comoving Kpc Around Z ∼2-7 Laes with Subaru Hsc-Ssp and Chorus Data

We conduct intensity mapping to probe for extended diffuse Lyα emission around Lyα emitters (LAEs) at z ∼2-7, exploiting very deep (∼26 mag at 5σ) and large-area (∼4.5 deg2) Subaru/Hyper Suprime-Cam narrowband (NB) images and large LAE catalogs consisting of a total of 1540 LAEs at z = 2.2, 3.3, 5.7, and 6.6 obtained by the HSC-SSP and CHORUS projects. We calculate the spatial correlations of these LAEs with ∼1-2-billion-pixel flux values of the NB images, deriving the average Lyα surface brightness (SBLyα ) radial profiles around the LAEs. By carefully estimating systematics such as fluctuations of sky background and point-spread functions, we detect Lyα emission at 100-1000 comoving kpc around z = 3.3 and 5.7 LAEs at the 3.2σ and 3.7σ levels, respectively, and tentatively (=2.0σ) at z = 6.6. The emission is as diffuse as ∼10-20-10-19 erg s-1 cm-2 arcsec-2 and extended beyond the virial radius of a dark matter halo with a mass of 1011 M. While the observed SBLyα profiles have similar amplitudes at z = 2.2-6.6 within the uncertainties, the intrinsic SBLyα profiles (corrected for the cosmological dimming effect) increase toward high redshifts. This trend may be explained by increasing hydrogen gas density due to the evolution of the cosmic volume. Comparisons with theoretical models suggest that extended Lyα emission around an LAE is powered by resonantly scattered Lyα photons in the CGM and IGM that originate from the inner part of the LAE and/or neighboring galaxies around the LAE