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Abstract This study analyzes the effects of bioclimate and masticatory factors on the regional variability of human cranial forms across 150 ethnic groups worldwide. Morphometric variables were generated using principal component analysis applied to 3D homologous models. Relationships between cranial form and bioclimate (temperature and precipitation) and masticatory factors (infratemporal space) were tested considering sampling bias due to past population movements during the late Pleistocene and/or early- to mid-Holocene. Cranial size correlated with thermal conditions, consistent with Bergmann’s rule. The length/breadth proportion of the neurocranium aligned with Allen’s rule for thermal adaptation, while no relationship with masticatory stress was found. Facial form responded to either climate or masticatory conditions, although the primary factor was unclear due to the high correlation between stresses. However, masticatory stress was identified as an equally significant factor behind facial flatness in cold regions, else than the effect of Allen’s rule. High narrowness of nasal and orbital openings correlated significantly with cold temperatures and cranial size, suggesting not only functional but also allometric effect. This study demonstrated the complexity of environmental influences on cranial form diversity, nonetheless suggested reduction of selective pressure on cranial form caused by natural environmental stress due to the development of civilization.

Abstract Background Symptomatic heart failure (HF) negatively affects the quantity and quality of skeletal muscles. However, the association between asymptomatic HF and skeletal muscle function remains unclear. We aimed to use ultrasonography to elucidate the association between asymptomatic HF and skeletal muscle function in community-dwelling older adults. Methods This cross-sectional study comprised community-dwelling older adults aged ≥ 60 years who could perform activities of daily living independently and had never had symptomatic HF (n = 52, 76.3 ± 6.1 years). The participants were classified into three groups namely, non-HF (n = 26), stage A (n = 19), and stage B (n = 7) according to the HF stage criteria of the American Heart Association /American College of Cardiology /Heart Failure Society of America guideline. Skeletal muscle quantity and quality were assessed using ultrasonography (thickness and echo intensity) of the rectus femoris (RF) and vastus intermedius (VI) muscles. The group effects on muscle thickness and echo intensity in each group were assessed using a multivariate analysis. Results Both muscles consistently demonstrated significant group effects on the thickness and echo intensity. Thicknesses of the RF (p = 0.020) and VI (p = 0.035) were lower in the stage B group than that in the non-HF group. The echo intensities in the RF (p = 0.006) and VI (p = 0.009) were higher in the stage B group than that in the non-HF group. Conclusion Asymptomatic HF negatively associated with the characteristics of skeletal muscle function, as assessed by ultrasonography in community-dwelling older adults. The stage B HF contributes to reduced skeletal muscle function as well as symptomatic HF.

In general, the life of a rolling bearing is calculated as the total number of rotations until rolling fatigue occurs on the raceway. However, when rolling bearings are used under light loads and high rotational speeds, they are damaged not by rolling fatigue on the raceways but by cage wear due to lubrication life. In such cases, the conventional method for calculating the rolling bearing life is not applicable. Rolling bearings for traction motors of railway vehicles (hereafter referred to as traction motor bearings) are one example of this and are replaced primarily due to lubrication life. However, there is no practical way to calculate lubrication life and these rolling bearings are replaced empirically. The purpose of this paper is to obtain basic data to create a method for calculating lubrication life. Therefore, traction motor bearings were rotated under conditions like actual operating conditions to reproduce damage due to lubrication life. As a result, damage due to lubrication life could be reproduced, so the next step was to investigate the effect on lubrication life when the operating conditions of traction motor bearings were varied as parameters. The parameters considered were “bearing temperature”, “vibration acceleration”, and “grease mass”. As a result of these verifications, lubrication life decreased exponentially when the bearing temperature was increased. In addition, lubrication life decreased exponentially when vibration acceleration was increased. Furthermore, lubrication life increased logarithmically when the grease mass was increased. The effects of these verified parameters on lubrication life could all be formulated within this paper.

Background: A prospective evaluation of non-alcoholic fatty liver disease (NAFLD) during induction therapy for acute lymphoblastic leukemia (ALL) has not been performed. Herein, we prospectively investigated the frequency, risk factors, and outcomes of NAFLD during induction therapy in children and adolescents with B-cell precursor ALL (BCP-ALL). Methods: This study enrolled 74 newly diagnosed BCP-ALL cases aged 1 year and older who were admitted to our department between January 2011 and December 2020. Median age was 6.6 years (1.3–17.5 years). Plain computed tomography (CT) of the upper abdomen was performed before induction therapy, and on days 15 and 29 after initiation of induction therapy. Patients with a liver/spleen CT ratio

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: −3.5 ± 9.4 mL/min/1.73 m2/year, post: −0.4 ± 6.3 mL/min/1.73 m2/year, p < 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: −2.0 ± 10.9 mL/min/1.73 m2/year, post: −1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits—especially annual eGFR decline—of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.

Abstract Background To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP). Methods VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012–2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases. Results Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4–70.5% (HZ), 67.0–90.0% (MTB), 18.3–63.4% (NTM), and 20.0–45.0% (PJP) for prevalent cases, and 69.1–70.9% (HZ), 58.6–87.9% (MTB), 10.0–56.0% (NTM), and 22.6–51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM. Conclusions VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.

Given Japan's unique social background, it is critical to understand the current risk factors for postpartum hemorrhage (PPH) to effectively manage the condition, especially among specific groups. Therefore, this study aimed to identify the current risk factors for PPH during planned cesarean section (CS) in Japan. This multicenter retrospective cohort study was conducted in two tertiary maternal-fetal medicine units in Fukushima, Japan and included 1,069 women who underwent planned CS between January 1, 2013, and December 31, 2022. Risk factors for PPH (of > 1000 g and > 1500 g) were assessed using multivariate logistic regression analysis, considering variables such as maternal age, parity, assisted reproductive technology (ART) pregnancy, pre-pregnancy body mass index (BMI), uterine myoma, placenta previa, gestational age at delivery, birth weight categories, and hypertensive disorders of pregnancy (HDP). Multivariate linear regression analyses were conducted to predict estimated blood loss during planned CS. ART pregnancy, a pre-pregnancy BMI of 25.0-29.9 kg/m2, and uterine myoma increased PPH risk at various levels. Maternal smoking increased the risk of >1500 g PPH (adjusted odds ratio: 3.09, 95% confidence interval [CI]: 1.16-8.20). Multivariate linear analysis showed that advanced maternal age (B: 83 g; 95% CI: 27-139 g), ART pregnancy (B: 239 g; 95% CI: 121-357 g), pre-pregnancy BMI of 25.0-29.9 kg/m2 (B: 74 g; 95% CI: 22-167 g), uterine myoma (B: 151 g; 95% CI: 47-256 g), smoking (B: 107 g; 95% CI: 13-200 g), and birth weight > 3,500 g (B: 203 g; 95% CI: 67-338 g) were associated with blood loss during planned CS. Considering a patient's clinical characteristic may help predict bleeding in planned CSs and help improve patient safety.

Nephroblastomatosis (NBM) is a precursor of Wilms tumor. We herein report a case in which Wilms tumor was initially suspected and the affected kidney was removed. The tumor was subsequently diagnosed as intralobar NBM and a favorable outcome was achieved with postoperative chemotherapy. A 2-year-old boy who presented with gross hematuria was found to have an enlarged left kidney with hydronephrosis. Needle biopsy of the left kidney suggested Wilms tumor and left nephrectomy was performed. The tumor was histopathologically diagnosed as intralobar NBM. Although NBM is regarded as a precancerous lesion, a definite treatment plan has not yet been established. In the present case, we used a similar chemotherapy regimen to that for Wilms tumor. Eight years after the completion of chemotherapy, Wilms tumor has not developed or recurred. Appropriate management plans need to be developed by accumulating similar cases.

Key Clinical Message Disseminated carcinomatosis of the bone marrow is rare. We present such a case, which is useful for raising awareness about the importance of early diagnosis and treatment of carcinomas complicated by disseminated carcinomatosis of the bone marrow. Abstract This is the first autopsy report of disseminated carcinomatosis of the bone marrow (DCBM) in esophageal adenocarcinoma. Advanced poorly differentiated adenocarcinoma with signet ring cell carcinoma arising in Barrett's esophagus caused disseminated intravascular coagulation (DIC) with extensive bone marrow metastasis, resulting in death from cerebral hemorrhage. Although DCBM due to malignancy is rare with poor prognosis, it should be considered in malignancies associated with DIC, and prompt initiation of chemotherapy is the only way to improve the patient's prognosis.

Abstract Individual sunspot observations have formed a ground basis of international sunspot number, a unique reference for long‐term solar variability in the centennial timescale. The original datasets were subjected to exploitations and analyses upon the recalibrations of the sunspot number series. In this context, this study reviewed and analysed original sunspot records and their databases in the Kawaguchi Science Museum (KSM) in Japan. KSM hosts sunspot drawings and logbooks from 1972 to 2013. This dataset has a longer chronological coverage than what was known to the scientific community (1981–2010). These records have been digitized and publicized in a museum database, which allows users to access individual sunspot drawings and numerical data in KSM logbooks. These records are highly homogeneous as a single observer's dataset (Hitoshi Takuma), who used a 15‐cm refractor at the Kawaguchi Juvenile Museum in 1972–2003 and a 20‐cm refractor at KSM in 2003–2013. We also reviewed the Takuma data series, his monthly observation days (21.3 days/month), sunspot number in the whole disk and each hemisphere, and sunspot positions in a butterfly diagram. We also assessed Takuma's data stability in comparison with the international sunspot number and reference datasets of the SILSO. Takuma's data appear stable until 2003, when he changed the observation site and instrument. His data stability was quantitatively compared with the SILSO reference datasets, confirming the substantial long‐term stability of the data and establishing its reliability as an alternative reference for sunspot number recalibration.

Abstract Background Dystocia is a common obstetric complication among nulliparous women, which requires medical intervention and carries the risk of negative maternal and neonatal outcomes. Our aim was to examine the association between body mass index (BMI) and the occurrence of dystocia. We also identified cutoffs of gestational weight gain, based on pre-pregnancy BMI, associated with the risk of dystocia. Methods This was a multicenter, retrospective, cohort study conducted in two tertiary Maternal–Fetal medicine units in Fukushima, Japan. The study population included nullipara women who delivered at either of the two units between January 1, 2013, and December 31, 2020. Women (n = 2597) were categorized into six groups (G) based on their pre-pregnancy BMI: G1 ( 30.0 kg/m2 was an independent risk factor for dystocia. For women with a pre-pregnancy BMI

Abstract Background Evaluation of micromotion in various activities in daily life is essential to the assessment of the initial fixation of cementless short stems in total hip arthroplasty. This study sought to evaluate three-dimensionally the micromotion of two types of cementless short stems. Methods Two types of stems were used: the Fitmore stem with a rectangular cross-section (rectangular stem) and the octagonal-oval GTS stem with fins (finned stem). Finite element analysis was used to calculate the micromotion of two activities that place a heavy load on the stem (single-leg stance and stair climbing). Three values were measured: the magnitude of micromotion (mean and 95th percentile), the location of micromotion above the 95th percentile value, and the directions of the micromotion vector. Results 1. There was no significant difference in the magnitude of the micromotion between the rectangular stem and finned stem groups for single-leg stance or stair climbing. 2. In both groups, the micromotion was greatest at the proximal and distal ends. 3. The direction of the micromotion was similar in both groups; internal rotation occurred from the distal to the middle of the stem during stair climbing. Conclusions The rectangular stem had comparable initial fixation to that of the finned stem. In both models, the micromotion was greater at the proximal and distal ends. The direction of the micromotion was not dependent on the stem shape but on the direction of the load on the artificial femoral head. These results will be important for stem selection and future stem development.

In the pursuit of understanding the population of stellar remnants within the Milky Way, we analyze the sample of ∼950 microlensing events observed by the Spitzer Space Telescope between 2014 and 2019. In this study we focus on a subsample of nine microlensing events, selected based on their long timescales, small microlensing parallaxes, and joint observations by the Gaia mission, to increase the probability that the chosen lenses are massive and the mass is measurable. Among the selected events we identify lensing black holes and neutron star candidates, with potential confirmation through forthcoming release of the Gaia time-series astrometry in 2026. Utilizing Bayesian analysis and Galactic models, along with the Gaia Data Release 3 proper-motion data, four good candidates for dark remnants were identified: OGLE-2016-BLG-0293, OGLE-2018-BLG-0483, OGLE-2018-BLG-0662, and OGLE-2015-BLG-0149, with lens masses of ${3.0}_{-1.3}^{+1.8}\,{M}_{\odot }$ , ${4.7}_{-2.1}^{+3.2}\,{M}_{\odot }$ , ${3.15}_{-0.64}^{+0.66}\,{M}_{\odot }$ and ${1.40}_{-0.55}^{+0.75}\,{M}_{\odot }$ , respectively. Notably, the first two candidates are expected to exhibit astrometric microlensing signals detectable by Gaia, offering the prospect of validating the lens masses. The methodologies developed in this work will be applied to the full Spitzer microlensing sample, populating and analyzing the timescale ( t _E ) versus parallax ( π _E ) diagram to derive constraints on the population of lenses in general and massive remnants in particular.

We present high angular resolution imaging that detects the MOA-2008-BLG-379L exoplanet host star using Keck adaptive optics and the Hubble Space Telescope. These observations reveal host star and planet masses of M _host = 0.434 ± 0.065 M _⊙ and m _p = 2.44 ± 0.49 M _Jupiter . They are located at a distance of D _L = 3.44 ± 0.53 kpc, with a projected separation of 2.70 ± 0.42 au. These results contribute to our determination of exoplanet host star masses for the Suzuki et al. statistical sample, which will determine the dependence of the planet occurrence rate on the mass and distance of the host stars. We also present a detailed discussion of the image-constrained modeling version of the eesunhong light-curve modeling code that applies high angular resolution image constraints to the light-curve modeling process. This code increases modeling efficiency by a large factor by excluding models that are inconsistent with the high angular resolution images. The analysis of this and other events from the Suzuki et al. statistical sample reveals the importance of including higher-order effects, such as microlensing parallax and planetary orbital motion, even when these features are not required to fit the light-curve data. The inclusion of these effects may be needed to obtain accurate estimates of the uncertainty of other microlensing parameters that affect the inferred properties of exoplanet microlens systems. This will be important for the exoplanet microlensing survey of the Roman Space Telescope, which will use both light-curve photometry and high angular resolution imaging to characterize planetary microlens systems.

We measure the dependence of planet frequency on host star mass, M _L , and distance from the Galactic center, R _L , using a sample of planets discovered by gravitational microlensing. We compare the two-dimensional distribution of the lens-source proper motion, μ _rel , and the Einstein radius crossing time, t _E , measured for 22 planetary events from Suzuki et al. with the distribution expected from Galactic model. Assuming that the planet-hosting probability of a star is proportional to ${M}_{{\rm{L}}}^{m}{R}_{{\rm{L}}}^{r}$ , we calculate the likelihood distribution of ( m , r ). We estimate that $r={0.10}_{-0.37}^{+0.51}$ and $m={0.50}_{-0.70}^{+0.90}$ under the assumption that the planet-hosting probability is independent of the mass ratio. We also divide the planet sample into subsamples based on their mass ratio, q , and estimate that $m=-{0.08}_{-0.65}^{+0.95}$ for q < 10 ^−3 and ${1.25}_{-1.14}^{+1.07}$ for q > 10 ^−3 . Although uncertainties are still large, this result implies a possibility that, in orbits beyond the snowline, massive planets are more likely to exist around more massive stars whereas low-mass planets exist regardless of their host star mass.

Following Shin et al. (2023b), which is a part of the “Systematic KMTNet Planetary Anomaly Search” series (i.e., a search for planets in the 2016 KMTNet prime fields), we conduct a systematic search of the 2016 KMTNet subprime fields using a semi-machine-based algorithm to identify hidden anomalous events missed by the conventional by-eye search. We find four new planets and seven planet candidates that were buried in the KMTNet archive. The new planets are OGLE-2016-BLG-1598Lb, OGLE-2016-BLG-1800Lb, MOA-2016-BLG-526Lb, and KMT-2016-BLG-2321Lb, which show typical properties of microlensing planets, i.e., giant planets orbit M-dwarf host stars beyond their snow lines. For the planet candidates, we find planet/binary or 2L1S/1L2S degeneracies, which are an obstacle to firmly claiming planet detections. By combining the results of Shin et al. (2023b) and this work, we find a total of nine hidden planets, which is about half the number of planets discovered by eye in 2016. With this work, we have met the goal of the systematic search series for 2016, which is to build a complete microlensing planet sample. We also show that our systematic searches significantly contribute to completing the planet sample, especially for planet/host mass ratios smaller than 10 ^−3 , which were incomplete in previous by-eye searches of the KMTNet archive.

We present the analysis of the microlensing event OGLE-2014-BLG-0221, a planetary candidate event discovered in 2014. The photometric light curve is best described by a binary-lens single-source model. Our light-curve modeling finds two degenerate models, with event timescales of t _E ∼ 70 days and ∼110 days. These timescales are relatively long, indicating that the discovered system would possess a substantial mass. The two models are similar in their planetary parameters with a Jupiter mass ratio of q ∼ 10 ^−3 and a separation of s ∼ 1.1. Bayesian inference is used to estimate the physical parameters of the lens, revealing that the shorter timescale model predicts 65% and 25% probabilities of a late-type star and white dwarf host, respectively, while the longer timescale model favors a black hole host with a probability ranging from 60% to 95%, under the assumption that stars and stellar remnants have equal probabilities of hosting companions with planetary mass ratios. If the lens is a remnant, this would be the second planet found by microlensing around a stellar remnant. The current separation between the source and lens stars is 41–139 mas depending on the models. This indicates the event is now ready for high-angular-resolution follow-up observations to rule out either of the models. If precise astrometric measurements are conducted in multiple bands, the centroid shift due to the color difference between the source and lens would be detected in the luminous lens scenario.

Abstract Bone growth is most remarkable during puberty. This study aimed to clarify the effects of physique and physical strength on bone mineral density and bone metabolism markers during puberty to help improve bone growth during puberty and prevent future osteoporosis. There were 277 pubertal participants (125 boys and 152 girls) in this survey from 2009 to 2015, all aged 10/11 and 14/15 years. The measures included physical fitness/physique indices (such as muscle ratio etc.), grip strength, bone density (osteo sono-assessment index, OSI), and bone metabolism markers (bone-type alkaline phosphatase and type I collagen cross-linked N-telopeptide). At 10/11-years-old for girls, a positive correlation was found between body size/grip strength and OSI. At 14/15-year-old for boys, all body size factors/grip strength were positively correlated with OSI. The change in body muscle ratio was positively correlated with change in OSI for both sexes. The height, body muscle ratio and grip strength at 10/11-year-old were significantly associated with OSI (positively) and bone metabolism markers (negatively) at 14/15-year-old for both sexes. Adequate physique building after 10/11 years for boys and before 10/11 years for girls may be effective in increasing peak bone mass.

Abstract Background In reproductive medicine, vitamin D (VitD) is of particular interest because its deficiency has been linked to various infertility issues. Thus, preconception care, including appropriate VitD supplementation, is essential, especially in women using assisted reproductive technology (ART). Despite the therapeutic benefits of VitD, adverse events due to a high daily intake may influence obstetric outcomes. However, the effects of either low or high preconception VitD intake on obstetric outcomes, including the outcomes in women who used ART, remain unclear. Therefore, the aim of this study was to examine the association between pre-pregnancy daily VitD intake and obstetric outcomes in Japanese women, including those who conceived through ART. Methods Data were obtained from the Japan Environment and Children’s study database comprising 92,571 women recruited between January 2011 and March 2014 in Japan. Participants were categorized into five quintiles according to pre-pregnancy VitD intake (Q1 and Q5 had the lowest and highest VitD intake, respectively) and stratified according to the use of ART. Multiple logistic regression was performed to identify the effects of pre-pregnancy VitD intake on preterm birth (PTB), low-birth weight infant (LBW), and small for gestational age (SGA). Results Using Q3 (middle VitD intake) as a reference, our analysis revealed that Q5 (highest VitD intake) showed an increased risk of LBW

Abstract Background This study aimed to evaluate whether hypereosinophilia is a clinical biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma treated with nivolumab plus ipilimumab. Methods This was a retrospective cohort study conducted at Jichi Medical University Saitama Medical Center between January 2018 and December 2020. In total, 12 patients with renal cell carcinoma who presented with immune checkpoint inhibitor-induced hypopituitarism were enrolled in this study. The clinical parameters and symptoms at baseline, last visit, and onset of hypopituitarism were analyzed. Results The median period from the initial treatment with immune checkpoint inhibitors to the onset of hypopituitarism was 82.5 (range: 56–196) days. Most patients developed hypopituitarism within 6 months. One patient presented with hypophysitis and 11 patients presented with isolated adrenocorticotropic hormone deficiency. The major symptoms noted at onset were fatigue (66.7%) and loss of appetite (41.7%). None of the patients had symptoms during the last visit. However, four developed hypereosinophilia. Eosinophil fraction (%) and eosinophil count (/µL) increased during the last visit and at the onset of hypopituitarism, respectively. The serum sodium and plasma glucose levels were similar. Conclusions The eosinophil count increased before the onset of hypopituitarism. Thus, hypereosinophilia can be an early predictor of hypopituitarism.

In this study, we examined information leakage in photoplethysmogram (PPG)-based biometric authentication and assessed an attack against authentication based on the information leakage. Several approaches have been proposed to apply PPG to biometric authentication using a wearable device; however, there may be several attacks against PPG-based authentication. One of the attacks is a “presentation attack” (PA), which utilizes the information leakage originating from the various PPG measurement sites on a body. The PA records the victim’s PPG stealthily on non-genuine measurement sites and transmits it to the PPG sensor to break the authentication. We examined the information leakage and assessed the PA by evaluating feature values extracted from the PPG signals. We recorded the PPG signals of 12 participants on their fingertips and wrists. We compared the feature values extracted from the recorded PPG signals by computing the differences, correlation coefficients, and mutual information to examine the leakage of information required for the PPG-based authentication. We then assessed the feasibility of a PA based on existing PPG-based authentication algorithms and evaluated the contribution of each value to authentication and PA by computing the permutation importance of all feature values. The experimental results indicated that there might be information leakage and selection of feature values to reduce the feasibility of the PA up to 62.8 %.

Background: Antibiotics have been widely and efficaciously used for febrile neutropenia in pediatric patients. However, reports are scant regarding the risk factors for recurrent fever after discontinuation of antibiotics in a neutropenic state. Here, we investigated these factors using data from our previously reported randomized study regarding meropenem and piperacillin/tazobactam for pediatric patients with febrile neutropenia. Procedure: We analyzed a total of 170 febrile episodes where first line antibiotic treatment was effective and discontinued before neutrophil recovery. Results: Recurrent fever was observed in 31 episodes (18%). The median interval from antibiotics discontinuation to recurrent fever was 5 days (0–27 days). Risk factors for recurrent fever were: incomplete remission of original disease; and high white blood cell count, neutrophil count, and C reactive protein levels at start of antibiotics. Moreover, lower neutrophil count at discontinuation of antibiotics, duration of neutropenia, and onset day of febrile neutropenia from start of neutropenia were also risk factors of recurrent fever. In multivariate analysis, neutrophil count at discontinuation of antibiotics

Background : : Febrile neutropenia (FN) remains an important complication in pediatric cancer patients. The present study compared the efficacy of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous immunoglobulin (IVIG) as second-line therapy for FN in pediatric patients. Methods : : As first-line treatment for FN, 394 episodes in 99 patients were randomly assigned to receive PIPC/TAZ (360 mg/kg/day, maximum 18 g/day) or MEPM (120 mg/kg/day, maximum 3 g/day). Eighty-four episodes in 42 patients were judged as failures, and, thus, were enrolled for second-line treatment. In second-line treatment, antibiotics were switched to MEPM or PIPC/TAZ, and episodes were further randomized for treatment with or without concomitant IVIG at 100 mg/kg/day (maximum 5 g/day) for 3 consecutive days. Results : : The total success rate of second-line treatment was 50.0% (52.0% in PIPC/TAZ and 47.2% in MEPM with or without IVIG, P=0.826). The success rates of patients treated with (IVIG+ group) and without IVIG (IVIG− group) were 53.8 and 46.7%, respectively (P=0.662). In the IVIG+ group, the success rate of patients younger than 8 years old was 78.6%, which was significantly higher than that of those aged 8 years and older (40.0%, P=0.043). Conclusion : : PIPC/TAZ and MEPM were equally effective as second-line treatment. Concomitant IVIG was also effective, particularly in patients younger than 8 years.

Abstract Background Pregnancy in a rudimentary horn is an extremely rare type of ectopic pregnancy. A rudimentary uterine horn pregnancy is associated with a risk of spontaneous rupture and bleeding during surgery due to the increased uterine blood flow. Recent advances in imaging modalities have enabled laparoscopic surgery to be performed in cases without rupture in the early stages of pregnancy. However, there are few reports of successful pregnancies and deliveries after treatment of rudimentary horn pregnancies. We report the successful management of a case of non-communicating rudimentary horn pregnancy by local injection of methotrexate followed by complete laparoscopic excision along with a review of the literature. Case presentation The patient was a 29-year-old Japanese woman, gravida 2, nullipara. She was diagnosed with a left unicornuate uterus with a right non-communicating rudimentary horn on hysterosalpingography and magnetic resonance imaging. A gestational sac with a heartbeat was observed in the right rudimentary uterine horn at 6 weeks of gestation. A diagnosis of ectopic pregnancy in a non-communicating rudimentary horn was made. Color Doppler detected multiple blood flow signals around the gestational sac, which were clearly increased compared to the left unicornuate uterus. Her serum human chorionic gonadotropin level was 104,619 mIU/ml. A 100 mg methotrexate injection into the gestational sac was administered, and laparoscopic surgery was performed on day 48 after the methotrexate treatment. The right rudimentary horn and fallopian tube were successfully excised with minimal bleeding. A spontaneous normal pregnancy was established 6 months after the surgery. The pregnancy was uneventful, and a baby girl was born by elective cesarean section at 38w0d. Conclusion Combined local methotrexate injection and laparoscopic surgery are safe treatment options for patients with a unicornuate uterus with a non-communicating rudimentary horn pregnancy.

Abstract Ovarian tumors are rarely associated with abscesses. Herein, an autopsy case of an ovarian mucinous cystic tumor complicated by an abscess, along with a review of previous cases, suggests the necessity of considering ovarian abscess as a cause of inflammation in patients with the ovarian tumors.

Abstract Volatile compounds in food play a crucial role in affecting food quality and consumer preference, but the volatile compounds in olive oil are not fully understood due to the matrix effect of oil. The oiling-out assisted liquid–liquid extraction (OA-LLE), which we previously reported, is an effective method for isolating volatile compounds from edible oils with a strong matrix effect. However, when we apply OA-LLE to extra virgin olive oil (EVOO), the aromatic extracts contain non-volatile compounds such as pigments because of solvent-based extraction. Solvent-assisted flavor evaporation (SAFE) can remove such non-volatiles from extracts, but SAFE is affected by a matrix effect during distillation, resulting in a decrease in performance. By combining the advantages of OA-LLE and SAFE, we propose an effective approach, OA-LLE followed by SAFE (OA-LLE + SAFE), for extracting aroma compounds from EVOO. The “two assists” should help to better understand the native aroma profile of EVOO.

Implantation of the blastocyst into the uterus is a specific and essential process for mammalian embryonic development. In mice, implantation is initiated from the mural trophectoderm of the blastocyst and the mTE controls implantation progression by acquiring the ability to attach and invade into the endometrium while differentiating into primary trophoblast giant cells. Nevertheless, it remains largely unclear when and how the mTE differentiates and acquires this ability during implantation. Here, by RNA sequencing analysis with the pre- and peri-implantation mTE, we show that the mTE undergoes stage-specific and dynamic changes of gene expression during implantation. We also reveal that the mTE begins down-regulating Cdx2 and up-regulating differentiation marker genes during the peri-implantation stage. In addition, using trophectoderm (TE) -specific lentiviral vector-mediated gene transduction, we demonstrate that TE-specific Cdx2 overexpression represses differentiation of the mTE into the primary trophoblast giant cells. Moreover, we reveal that TE-specific Cdx2 overexpression also represses the up-regulation of cell adhesion- and migration-related genes, including Slc6a14, Slc16a3, Itga7, Itgav and Itgb3, which are known to regulate migration of trophectoderm cells. In particular, the expression of Itgb3, an integrin subunit gene, exhibits high inverse correlation with that of Cdx2 in the TE. Reflecting the down-regulation of the genes for TE migration, TE-specific Cdx2 overexpression causes suppression of the blastocyst outgrowth in vitro and abnormal progression of implantation in vivo. Thus, our results specify the time-course changes of global gene expression in the mTE during implantation and uncover the significance of Cdx2 down-regulation for implantation progression.

Helical gears are commonly used in the gear units of railway vehicles in Japan, and the bearing types used for the gear units are tapered roller bearings. In this gear unit bearing arrangements, it is important to appropriately adjust the combined clearance, called the endplay, of the two bearings supporting the pinion to prevent the damage such as seizure. Our previous research has shown that the smaller the endplay value at gear unit assembly (Initial endplay value) and the lower the ambient temperature, the greater the decrease in endplay value during rotation and the greater the risk of seizure. One of method to prevent seizure is to increase the initial endplay value, but this means an increase in the internal clearance of the bearings, which may reduce the fatigue life of the bearings or cause damage to their cages due to increased vibration. In order to prevent seizure without reducing bearing life, therefore, this study has examined the use of cylindrical roller bearings with ribs that allow a certain degree of axial displacement of inner rings and outer rings, and has compared its performance with that of a conventional structure using tapered roller bearings through various rotating tests. As a result, it is found that the temperature rise immediately after the start of rotation and torque of pinion shaft are lower for the cylindrical roller bearings with ribs than for the tapered roller bearings during the rotation test using the actual gear unit. Further, the results of rotating tests under the radial and axial loads for the pinion bearings alone showed that the torque of cylindrical roller bearings with ribs tended to be lower than that of tapered roller bearings under a large range of flow rate and temperature of lubricants.

When rolling bearings are used under light loads and high rotational speeds, their life may be determined by cage wear rather than raceway flaking. Under these operating conditions, the life and reliability of the bearings can be improved by reducing cage wear. To reduce cage wear, it is necessary to measure and analyze the contact forces acting on the cage due to the interactions between the roller and the cage pocket. In this paper, a measurement system capable of measuring “the contact forces between the roller and the cage pocket” and “the cage center displacement” at the same time has been constructed. Measurements have been conducted using this system for a cylindrical roller bearing at various rotational speeds. As a result of measuring the contact forces, it has been found that “the force to accelerate the cage” is generated continuously in the load zone of the bearing, while “the force to decelerate the cage” is generated intermittently in the non-load zone of the bearing. Since the contact forces are not constant during one rotation of the cage, the impulses due to the interactions have been calculated to evaluate not only the contact force but also the contact time. Results indicate that the impulses per rotation of the cage caused by each force show a tendency to decrease up to 2000 min-1 of rotational speed and not to almost change at higher speeds. In addition, it has been found that the cage center displacement measured becomes a constant velocity circular motion when the rotational speed exceeds 2000 min-1. These findings suggest that the contact between the roller and the cage can be easily modeled when the rotational speed exceeds 2000 min-1. The analysis based on this model created is in general agreement with the impulses obtained from the measurement results.

Abstract Background Enterococcus casseliflavus is rarely isolated from human specimens. To the best of our knowledge, there are no reports on its detailed treatment course and prognosis. Here, we present the first known case of E. casseliflavus endocarditis with a detailed treatment course. Case presentation An 86-year-old Japanese woman was transferred to the emergency department with dyspnoea, wheezing, and lumbago. Her medical history included hypertension, chronic kidney disease, idiopathic interstitial pneumonia, and rectal carcinoma. Physical examination revealed expiratory wheezes and a diastolic murmur (Levine 2/6) at the 4th right sternal border. Chest radiography revealed bilateral interstitial opacities and slight cardiac dilatation. Transthoracic echocardiography demonstrated the presence of mobile vegetation with perforation, prolapse, and regurgitation of the aortic valve. With a suspicion of infective endocarditis, we started administering intravenous ampicillin/sulbactam. Thereafter, blood cultures identified E. casseliflavus through matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The antimicrobial treatment was then switched to ampicillin plus gentamicin. The patient underwent aortic valve replacement on the thirteenth hospital day. She was administered intravenous ampicillin and gentamicin for 6 weeks. The patient was discharged 8 weeks after admission. Conclusions Our case demonstrated that E. casseliflavus could cause infective endocarditis, which can be successfully treated with a 6-week regimen of ampicillin and gentamicin in combination with proper surgical treatment.

Abstract Sodium-glucose cotranspsorter-2 (SGLT2) inhibitors (SGLT2i) involve loss of skeletal muscle mass, potentially leading to inadequate HbA1c reduction in type 2 diabetes (T2DM), since muscle mass is related to insulin sensitivity. The benefit of protein-enriched diet for improving HbA1c in SGLT2i-treated T2DM patients remains unclear. We conducted a multicenter, double-blind, randomized, controlled, investigator-initiated clinical trial. 130 T2DM patients treated with dapagliflozin (5 mg) were randomized to isoenergic protein-rich formula diet (P-FD) or fat-rich FD (F-FD) (1:1 allocation) to replace one of three meals/day for 24 weeks. Primary outcome was change in HbA1c. Secondary outcomes were changes in serum insulin, body composition and other metabolic parameters. Although HbA1c decreased significantly in both groups [mean (95% confidence interval) − 0.7% (− 0.9 to − 0.5) in P-FD, − 0.6% (− 0.8 to − 0.5) in F-FD], change in HbA1c was not significantly different between the two groups (P = 0.4474). Fasting insulin and body fat mass decreased, while HDL-cholesterol increased significantly in P-FD, and these changes were significantly greater compared with F-FD (all, P

Cylindrical roller bearings used in traction motors for railway vehicles are used at high rotational speeds and under light loads. Under these operating conditions, the life due to cage wear is much shorter than the life due to raceway fatigue. Therefore, bearing life can be extended by reducing cage wear. The authors thought that to reduce cage wear, it is necessary to establish a dynamic analysis method for the contact between the roller and the cage, and to identify the wear mode of the cage. If cage wear follows Archard’s equation, then cage wear is proportional to the impulse caused by the contact between the rollers and the cage. Therefore, in this paper, a simple model consisting only of a roller and a cage was constructed, and the impulse was obtained via dynamic analysis. The impulses calculated by the dynamic analysis were in good agreement with those measured. In addition, the experiments showed that cage wear is proportional to the impulse and revealed the wear mode of the cage. These allow the method proposed in this paper to be used to predict cage wear and to determine bearing specifications to reduce cage wear.

Abstract Aims/Introduction We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced‐stage diabetic kidney disease (DKD). Materials and Methods The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) is a multicenter, open‐label, randomized controlled trial with a 5‐year follow‐up period. We randomly assigned 164 patients with advanced‐stage diabetic kidney disease (urinary albumin‐to‐creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2–2.5 mg/dL in men and 1.0–2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end‐stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention‐to‐treat population. Results The IT tended to reduce the risk of primary end‐points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43–1.11; P = 0.13). Meanwhile, the decrease in serum low‐density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05–1.23, P

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient’s condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood–brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. Conclusion We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.

The purpose of this paper is to understand the load state of pinion bearings used for a gear unit in an electric railway vehicle. For this purpose, a system capable of measuring the rolling element load distribution of the pinion bearing in an actual gear unit was constructed, and the measurement was conducted under the same conditions as in an actual railway vehicle. Generally, tapered roller bearings are used for pinion bearings in a face-to-face arrangement, which has an axial clearance (endplay value). Therefore, the effect of the endplay value on the rolling element load distribution was investigated by changing the endplay value at specified values, larger values, and smaller values. As a result of measuring the rolling element load, it was found that the rolling element load tended to increase as the transmission torque of the gear unit increased. In addition, large rolling element loads occurred only when the endplay value was smaller than the specified value. The reason for this is that the axial thermal expansion of the pinion shaft exceeded the endplay value, and the bearing became pressurized. The bearing loads (radial and axial loads) were determined from the measured rolling element loads, and it was found that under conditions where the endplay value was smaller than the specified value, the axial load was significantly higher, which could cause a reduction in bearing life and wear of the bearing. Finally, the load distribution factor of the bearing was determined for each condition. It was observed that the load distribution factor decreased as the endplay value increased, and that for the same endplay value, the load factor tended to be smaller for the conditions with lower torque. It was also found that the load distribution of the rolling elements does not change significantly except under conditions where the endplay value is smaller than the specified value.

Maintaining physical and mental health of older people is one of the important issues to be addressed in the aging society. Social capital, defined as the resources available to members of social groups, has recently attracted attention as a factor influencing public health. Most of the previous studies targeted various communities having different aging rates or population densities at once to examine the associations of social capital and health outcomes. However, the results of those studies are not always consistent. Moreover, because few studies have targeted a particular advanced aging society, associations of social capital and health at such societies have remained unknown. This study examined how social capital associates with health at a particular city having a very high aging rate and low population density. We targeted Iwamizawa city, Hokkaido, Japan, which is one of the most advanced aging areas, with an aging rate of 36.6% and a population density of 165/km2. We analyzed self-administered questionnaire data obtained from “HELLO (HEalth, Lifestyle, and LOcal community of Iwamizawa citizen) Study” in 2018. The sample comprised 1237 individuals aged 65 and older. Following previous studies, we regarded three items—social cohesion, reciprocity, and civic participation—as social capital indices, and targeted two health outcomes: self-rated health (SRH) and degree of depression. Multilevel Poisson regression analyses were used to calculate prevalence ratios (PRs). We found that at the individual-level, the PR (95% confidence interval) of having poor SRH among those with more civic participation was 0.81 (0.71–0.93), and that of being depressed among those with more social cohesion was 0.32 (0.21–0.51), even after adjusting for compositional factors. We also found that the community-level civic participation significantly correlated with aging rate. Our findings indicate that social capital positively associates with older people's health at the advanced aging city.

Abstract Aims/Introduction Studies have shown that sodium–glucose cotransporter 2 (SGLT2) inhibitors increased time‐in‐range (TIR; percentage of time glucose level remains between 3.9 and 10.0 mmol/L [70–180 mg/dL]) and decreased glycemic variability in patients with type 1 diabetes. The aim of this study was to investigate the effects of SGLT2 inhibitors on TIR, glycemic variability and glucose control in Japanese patients with type 1 diabetes in a real clinical setting. Materials and Methods We designed a single‐arm, retrospective cohort study to analyze data from patients starting to use ipragliflozin or dapagliflozin and who used a sensor‐based flash glucose monitoring system between February 2019 and August 2019. We measured TIR, time above range >180 mg/dL (percentage of time with glucose level of >180 mg/dL or >10.0 mmol/L), time below range

Objectives: The infectious diseases team at Kameda Medical Center, Japan, implemented a new outpatient parenteral antimicrobial therapy (OPAT) program in July 2012 and expanded the program with the support of home care services. This study reviews the OPAT program after 5.5 years of operation. Methods: We prospectively collected data about the age, sex, diagnoses, causative organisms, types of OPAT, modes of administration, selected antibiotics, treatment durations, bed days saved, outcomes, readmissions, and estimated cost reductions of all patients who were treated in the OPAT program from July 2012 to December 2017. Results: Of the 66 patients treated under the OPAT program, 45 (68.2%) were treated using clinic OPAT, and 21 (31.8%) were treated using homecare OPAT. The most commonly targeted organism was methicillin-susceptible Staphylococcus aureus. Continuous infusion with elastomeric pumps was employed in 55 patients (83.3%). Cefazolin was the most frequently used antibiotic (39.4%), followed by penicillin G (24.2%). The median OPAT duration was 13 days (range, 3–51), and the total bed days saved was 923. The estimated medical cost reduction was approximately 87,000 US dollars. Conclusions: Our experience shows that OPAT is a safe and feasible practice not only for efficient bed utilization and medical cost savings but also for better antimicrobial stewardship.

Abstract Background Invasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called “repeat pancreatectomy” to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors. Methods Twenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models. Results Of 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan–Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis. Conclusions Preoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.

Abstract Background Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging. Case presentation An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19–9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing. Conclusion It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.

Summary: The ex vivo production of platelets depleted of human leukocyte antigen class I (HLA-I) could serve as a universal measure to overcome platelet transfusion refractoriness caused by HLA-I incompatibility. Here, we developed human induced pluripotent cell-derived HLA-I-deficient platelets (HLA-KO iPLATs) in a clinically applicable imMKCL system by genetic manipulation and assessed their immunogenic properties including natural killer (NK) cells, which reject HLA-I downregulated cells. HLA-KO iPLATs were deficient for all HLA-I but did not elicit a cytotoxic response by NK cells in vitro and showed circulation equal to wild-type iPLATs upon transfusion in our newly established Hu-NK-MSTRG mice reconstituted with human NK cells. Additionally, HLA-KO iPLATs successfully circulated in an alloimmune platelet transfusion refractoriness model of Hu-NK-MISTRG mice. Mechanistically, the lack of NK cell-activating ligands on platelets may be responsible for evading the NK cell response. This study revealed the unique non-immunogenic property of platelets and provides a proof of concept for the clinical application of HLA-KO iPLATs. : T cells and antibodies or NK cells reject HLA-I-incompatible or HLA-I-deficient cells, respectively. Sugimoto and colleagues produced HLA-I null platelets from iPSCs in a clinically applicable system and found that platelets can circulate even in human NK cell-reconstituted mice. Potentially, universal HLA-KO platelets could treat patients suffering from platelet transfusion refractoriness caused by HLA-I incompatibility. Keywords: platelet, megakaryocyte, iPSC, HLA class I, natural killer cell, regenerative medicine, imMKCL, platelet transfusion, refractoriness, MSTRG mice, IL-15

Abstract Purpose To investigate the transition of CDX2 expression patterns in mouse trophectoderm (TE) and its regulatory mechanisms during implantation. Methods Mouse E3.5–4.5 blastocysts were used to immunostain CDX2, YAP, TEAD4, and ESRRB. Endogenous estrogen signaling was perturbed by administrating estrogen receptor antagonist ICI 182,780 or ovariectomy followed by administration of progesterone and β‐estradiol to elucidate the relationship between the transition of CDX2 expression patterns and ovarian estrogen‐dependent change in the uterine environment. Results CDX2 expression was gradually downregulated in the mural TE from E4.0 in vivo, whereas CDX2 downregulation was not observed in blastocysts cultured in KSOM. Fetal bovine serum (FBS) supplementation in KSOM induced CDX2 downregulation independently of blastocyst attachment to dishes. CDX2 downregulation in the mural TE was repressed by administration of ICI 182,780 or by ovariectomy, and administration of β‐estradiol into ovariectomized mice retriggered CDX2 downregulation. Furthermore, Cdx2 expression in the mural TE might be controlled by the YAP‐TEAD pathway. Conclusions CDX2 downregulation was induced heteronomously in the mural TE from E4.0 by uterus‐derived factors, the secretion of which was stimulated by ovarian estrogen.

We present an analysis of microlensing event OGLE-2019-BLG-0825. This event was identified as a planetary candidate by preliminary modeling. We find that significant residuals from the best-fit static binary-lens model exist and a xallarap effect can fit the residuals very well and significantly improves χ ^2 values. On the other hand, by including the xallarap effect in our models, we find that binary-lens parameters such as mass ratio, q , and separation, s , cannot be constrained well. However, we also find that the parameters for the source system such as the orbital period and semimajor axis are consistent between all the models we analyzed. We therefore constrain the properties of the source system better than the properties of the lens system. The source system comprises a G-type main-sequence star orbited by a brown dwarf with a period of P ∼ 5 days. This analysis is the first to demonstrate that the xallarap effect does affect binary-lens parameters in planetary events. It would not be common for the presence or absence of the xallarap effect to affect lens parameters in events with long orbital periods of the source system or events with transits to caustics, but in other cases, such as this event, the xallarap effect can affect binary-lens parameters.

We report the discoveries of low-mass free-floating planet (FFP) candidates from the analysis of 2006–2014 MOA-II Galactic bulge survey data. In this data set, we found 6111 microlensing candidates and identified a statistical sample consisting of 3535 high-quality single-lens events with Einstein radius crossing times in the range 0.057 < t _E /days < 757, including 13 events that show clear finite-source effects with angular Einstein radii of 0.90 < θ _E / μ as < 332.54. Two of the 12 events with t _E < 1 day have significant finite-source effects, and one event, MOA-9y-5919, with t _E = 0.057 ± 0.016 days and θ _E = 0.90 ± 0.14 μ as, is the second terrestrial-mass FFP candidate to date. A Bayesian analysis indicates a lens mass of ${0.75}_{-0.46}^{+1.23}$ M _⊕ for this event. The low detection efficiency for short-duration events implies a large population of low-mass FFPs. The microlensing detection efficiency for low-mass planet events depends on both the Einstein radius crossing times and the angular Einstein radii, so we have used image-level simulations to determine the detection efficiency dependence on both t _E and θ _E . This allows us to use a Galactic model to simulate the t _E and θ _E distribution of events produced by the known stellar populations and models of the FFP distribution that are fit to the data. Methods like this will be needed for the more precise FFP demographics determinations from Nancy Grace Roman Space Telescope data.

We present the first measurement of the mass function of free-floating planets (FFPs), or very wide orbit planets down to an Earth mass, from the MOA-II microlensing survey in 2006–2014. Six events are likely to be due to planets with Einstein radius crossing times t _E < 0.5 days, and the shortest has t _E = 0.057 ± 0.016 days and an angular Einstein radius of θ _E = 0.90 ± 0.14 μ as. We measure the detection efficiency depending on both t _E and θ _E with image-level simulations for the first time. These short events are well modeled by a power-law mass function, ${{dN}}_{4}/d\mathrm{log}M={({2.18}_{-1.40}^{+0.52})\times (M/8\,{M}_{\oplus })}^{-{\alpha }_{4}}$ dex ^−1 star ^−1 with ${\alpha }_{4}={0.96}_{-0.27}^{+0.47}$ for M / M _⊙ < 0.02. This implies a total of $f={21}_{-13}^{+23}$ FFPs or very wide orbit planets of mass 0.33 < M / M _⊕ < 6660 per star, with a total mass of ${80}_{-47}^{+73}{M}_{\oplus }$ star ^−1 . The number of FFPs is ${19}_{-13}^{+23}$ times the number of planets in wide orbits (beyond the snow line), while the total masses are of the same order. This suggests that the FFPs have been ejected from bound planetary systems that may have had an initial mass function with a power-law index of α ∼ 0.9, which would imply a total mass of ${171}_{-52}^{+80}{M}_{\oplus }$ star ^−1 . This model predicts that Roman Space Telescope will detect ${988}_{-566}^{+1848}$ FFPs with masses down to that of Mars (including ${575}_{-424}^{+1733}$ with 0.1 ≤ M / M _⊕ ≤ 1). The Sumi et al. large Jupiter-mass FFP population is excluded.

As a part of the “Systematic KMTNet Planetary Anomaly Search” series, we report five new planets (namely, OGLE-2016-BLG-1635Lb, MOA-2016-BLG-532Lb, KMT-2016-BLG-0625Lb, OGLE-2016-BLG-1850Lb, and KMT-2016-BLG-1751Lb) and one planet candidate (KMT-2016-BLG-1855), which were found by searching 2016 KMTNet prime fields. These buried planets show a wide range of masses from Earth-class to super-Jupiter-class and are located in both the disk and the bulge. The ultimate goal of this series is to build a complete planet sample. Because our work provides a complementary sample to other planet detection methods, which have different detection sensitivities, our complete sample will help us to obtain a better understanding of planet demographics in our Galaxy.

The PRime-focus Infrared Microlensing Experiment (PRIME) will be the first to conduct a dedicated near-infrared microlensing survey by using a 1.8 m telescope with a wide field of view of 1.45 deg ^2 at the South African Astronomical Observatory. The major goals of the PRIME microlensing survey are to measure the microlensing event rate in the inner Galactic bulge to help design the observing strategy for the exoplanet microlensing survey by the Nancy Grace Roman Space Telescope and to make a first statistical measurement of exoplanet demographics in the central bulge fields where optical observations are very difficult owing to the high extinction in these fields. Here we conduct a simulation of the PRIME microlensing survey to estimate its planet yields and determine the optimal survey strategy, using a Galactic model optimized for the inner Galactic bulge. In order to maximize the number of planet detections and the range of planet mass, we compare the planet yields among four observation strategies. Assuming the Cassan et al. mass function as modified by Penny et al., we predict that PRIME will detect planetary signals for 42–52 planets (1–2 planets with M _p ≤ 1 M _⊕ , 22−25 planets with mass 1 M _⊕ < M _p ≤ 100 M _⊕ , 19–25 planets 100 M _⊕ < M _p ≤ 10, 000 M _⊕ ), per year depending on the chosen observation strategy.

We analyze the MOA-2020-BLG-208 gravitational microlensing event and present the discovery and characterization of a new planet, MOA-2020-BLG-208Lb, with an estimated sub-Saturn mass. With a mass ratio $q={3.17}_{-0.26}^{+0.28}\times {10}^{-4}$ , the planet lies near the peak of the mass-ratio function derived by the MOA collaboration and near the edge of expected sample sensitivity. For these estimates we provide results using two mass-law priors: one assuming that all stars have an equal planet-hosting probability, and the other assuming that planets are more likely to orbit around more massive stars. In the first scenario, we estimate that the lens system is likely to be a planet of mass ${m}_{\mathrm{planet}}={46}_{-24}^{+42}\,{M}_{\oplus }$ and a host star of mass ${M}_{\mathrm{host}}={0.43}_{-0.23}^{+0.39}\,{M}_{\odot }$ , located at a distance ${D}_{L}={7.49}_{-1.13}^{+0.99}\,\mathrm{kpc}$ . For the second scenario, we estimate ${m}_{\mathrm{planet}}={69}_{-34}^{+37}\,{M}_{\oplus }$ , ${M}_{\mathrm{host}}={0.66}_{-0.32}^{+0.35}\,{M}_{\odot }$ , and ${D}_{L}={7.81}_{-0.93}^{+0.93}\,\mathrm{kpc}$ . The planet has a projected separation as a fraction of the Einstein ring radius $s={1.3807}_{-0.0018}^{+0.0018}$ . As a cool sub-Saturn-mass planet, this planet adds to a growing collection of evidence for revised planetary formation models.

RISC-V is equipped with physical memory protection (PMP) to prevent malicious software from accessing protected memory regions. PMP provides a trusted execution environment (TEE) that isolates secure and insecure applications. In this study, we propose a side-channel-assisted fault-injection attack to bypass isolation based on PMP. The proposed attack scheme involves extracting successful glitch parameters for fault injection from side-channel information under crossdevice conditions. A proof-of-concept TEE compatible with PMP in RISC-V was implemented, and the feasibility and effectiveness of the proposed attack scheme was validated through experiments in TEEs. The results indicate that an attacker can bypass the isolation of the TEE and read data from the protected memory region In addition, we experimentally demonstrate that the proposed attack applies to a real-world TEE, Keystone. Furthermore, we propose a software-based countermeasure that prevents the proposed attack.