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Mouse models are vital for assessing risk from environmental carcinogens, including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human–mouse difference in radiation‐related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data on cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age‐related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per‐lifespan basis (0.72‐ and 0.71‐fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 years per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species‐independent radiation‐induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation‐associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans. [ABSTRACT FROM AUTHOR]

Maturity‐Onset Diabetes of the Young (MODY) is a diabetes mellitus subtype caused by a single gene. The detection rate of the responsible gene is 27% in the United Kingdom, indicating that the causative gene remains unknown in the majority of clinically diagnosed MODY cases. To improve the detection rate, we applied comprehensive genetic testing using whole exome sequencing (WES) followed by Multiplex Ligation‐dependent Probe Amplification (MLPA) and functional analyses. Twenty‐one unrelated Japanese participants with MODY were enrolled in the study. To detect copy number variations (CNVs), WES was performed first, followed by MLPA analysis for participants who were negative on the basis of WES. Undetermined variants were analyzed according to their functional properties. WES identified 7 pathogenic and 3 novel likely pathogenic variants in the 21 participants. Functional analyses revealed that 1 in 3 variants was pathogenic. MLPA analysis applied to the remaining 13 undetermined samples identified 4 cases with pathogenic CNVs: 3 in HNF4A and 1 in HNF1B. Pathogenic variants were identified in 12 participants (12/21, 57.1%) – relatively high rate reported to date. Notably, one‐third of the participants had CNVs in HNF4A or HNF1B, indicating a limitation of WES‐only screening. [ABSTRACT FROM AUTHOR]

Previously, cytotoxic drugs were the only option for patients with non‐small cell lung cancer (NSCLC) and the prognosis was poor. However, molecularly targeted therapies and immune checkpoint inhibitors represent a breakthrough in the treatment of advanced NSCLC and have improved survival rates. In addition, advances in next‐generation sequencing (NGS) have revealed the landscape of genomic alterations in patients with different cancers, aiding in the development of new molecularly targeted drugs. The patient reported here was a 54‐year‐old woman with left lower lung adenocarcinoma. The lung cancer was staged as T2aN3M1a stageIVA 11 years ago. She had received seven regimens of chemotherapy for 11 years. Among these, pemetrexed (PEM) regimens particularly showed long‐term effects totaling more than 5 years. We performed NGS after disease progression of the seventh treatment. NGS revealed CD74‐ROS1 fusion and she was treated with entrectinib. She has been taking entrectinib for over 20 months now. Herein, we report a rare case of CD74‐ROS1‐positive lung adenocarcinoma diagnosed by NGS that achieved long‐term survival with cytotoxic drugs, especially PEM regimens. In patients showing favorable clinical response to PEM regimens, physicians should consider testing for ROS1/ALK rearrangement. [ABSTRACT FROM AUTHOR]

Convective vortices (whirlwinds) and dust devils (dust‐loaded vortices) are one of the most common phenomena on Mars. They reflect the local thermodynamical structure of the atmosphere and are the driving force of the dust cycle. Additionally, they cause an elastic ground deformation, which is useful for retrieving the subsurface rigidity. Therefore, investigating convective vortices with the right instrumentation can lead to a better understanding of the Martian atmospheric structures as well as the subsurface physical properties. In this study, we quantitatively characterized the convective vortices detected by NASA's InSight (∼13,000 events) using meteorological (e.g., pressure, wind speed, temperature) and seismic data. The evaluated parameters, such as the signal‐to‐noise ratio, event duration, asymmetricity of pressure drop profiles, and cross‐correlation between seismic and pressure signals, are compiled as a catalog. Using these parameters, we investigated (a) the vortex structure and (b) the subsurface physical properties. Regarding the first topic, we tried to illustrate the vertical vortex structure and its link to the shape of the pressure profiles by combining the asymmetrical features seen in the observed pressure drops and the terrestrial observations of dust devils. Our results indicate that most of the vortices move with the wall tilted in the advection direction. Concerning the second topic, selecting the highly correlated events between pressure perturbation and ground response, we estimated the subsurface rigidity at the InSight landing site down to 100 m depth. Our results indicate that the subsurface structure can be modeled with two layers having a transition at 5–15 m depth. Plain Language Summary: As frequently observed on Earth, convective vortices or dust‐loaded vortices are also seen on Mars. They reflect the local atmospheric structure and are the main driving force to lift the fine dust from the ground. In 2018, NASA's InSight succeeded in installing the meteorological and geophysical packages on Mars. That brought us, in particular, meteorological data with an extremely high temporal resolution, contributing to resolving local phenomena such as convective vortices. In this study, using InSight's meteorological (e.g., pressure, air temperature) and seismic data, we quantitatively characterize convective vortices to understand this phenomenon from both meteorological and geophysical aspects. Especially focusing on the asymmetricity of pressure drop profiles at vortex encounters and the correlation between the pressure variations and seismic signals, we investigated (a) a link between the shape of pressure drop profiles and the vertical vortex structure and (b) the ground rigidity structure by measuring the ground responses against the vortex‐related pressure variations. Consequently, first, we found that most of the vortices move with the wall tilted in the advection direction. Second, our results indicated that the subsurface structure can be modeled with two layers down to 100 m with a transition at 5–15 m depth. Key Points: We quantitatively characterized the Martian convective vortices observed by InSight's seismometer and meteorological instrumentsFocusing on the pressure drop profiles, we inferred a link between the asymmetricity and the vertical vortex structureWith the cataloged parameters, we performed a compliance analysis and evaluated the ground rigidity at the InSight landing site [ABSTRACT FROM AUTHOR]

Aim: To determine the impact of direct‐acting antiviral therapy on the long‐term prognosis of decompensated cirrhotic patients. Methods: A total of 37 patients with hepatitis C virus‐induced decompensated cirrhosis treated with sofosbuvir and velpatasvir (SOF/VEL group) were prospectively enrolled. For historical control, 65 hepatitis C virus‐positive decompensated cirrhotic patients who did not receive direct‐acting antiviral therapy were included (control group). The incidence rates of hepatocellular carcinoma (HCC), decompensated events with hospitalization, and overall survival were compared between both groups. Results: A total of 41 patients experienced decompensated events during 15.0 months in the control group, and six patients during 21.6 months in the SOF/VEL group. The cumulative incidence rates of decompensated events after 2 years were significantly higher in the control group (53.1%) than in the SOF/VEL group (14.5%; p < 0.001). A total of 27 patients died within 22.0 months in the control group, and three patients died within 25.6 months in the SOF/VEL group. The overall survival rates after 2 years were significantly lower in the control group (67.6%) than in the SOF/VEL group (91.3%; p = 0.010). A total of 13 patients in the control group developed HCC during 15.8 months, and 10 patients during 17.3 months in the SOF/VEL group. The HCC incidence rates after 2 years were 20.3% and 29.6% in the control and SOF/VEL groups, respectively, with no significant difference (p = 0.327). Conclusions: SOF/VEL therapy may suppress the development of decompensated events and improve the prognosis in decompensated cirrhotic patients; however, the incidence of HCC remains prevalent in these patients irrespective of SOF/VEL therapy. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) has become a worldwide outbreak, and it can cause various symptoms and complications. However, pneumothorax secondary to COVID‐19 is relatively uncommon. We herein report a 60‐year‐old man with bilateral refractory pneumothorax with severe COVID‐19. In patients with poor general health and who are difficult to undergo surgery for pneumothorax post‐COVID‐19, internal treatments such as chest drainage, bronchial occlusion, and pleurodesis are essential to relieving refractory pneumothorax. It also indicates that autologous blood patch pleurodesis is a useful method in terms of efficacy and side effects. Bilateral pneumothorax secondary to COVID‐19 is a very rare complication and can be refractory. In patients with poor general condition and who are unfit for surgery, combining internal treatments (chest drainage, pleurodesis, and bronchial occlusion) is essential for relieving refractory pneumothorax. [ABSTRACT FROM AUTHOR]

The intense seismic scattering seen in Apollo lunar seismic data is one of the most characteristic features, making the seismic signals much different from those observed on the Earth. The scattering is considered to be attributed to subsurface heterogeneity. While the heterogeneous structure of the Moon reflects the past geological activities and evolution processes from the formation, the detailed description remains an open issue. Here, we present a new model of the subsurface heterogeneity within the upper lunar crust derived through a full 3D seismic wave propagation simulation. Our simulation successfully reproduced the Apollo seismic observations, leading to a significant update of the scattering properties of the Moon. The results showed that the scattering intensity of the Moon is about 10 times higher than that of the heterogeneous region on the Earth. The quantified scattering parameters could give us a constraint on the surface evolution process of the Moon and enable the comparative study for answering a fundamental question of why the seismological features are different on various planetary bodies. Plain Language Summary: In the past Apollo missions, several seismometers were installed on the nearside of the Moon and they brought us the first seismic records from an extraterrestrial body. The derived lunar seismic data surprised us because of their extremely long duration (1–2 hr) and spindle‐shaped form, which were barely observed on Earth. These characteristics, which are different from earthquakes, are thought to reflect the subsurface heterogeneity. However, the inhomogeneous structure within the lunar crust is poorly constrained. To improve our knowledge of wave propagation on an extraterrestrial body, this study evaluated the subsurface heterogeneity through 3D seismic wave propagation simulation. After running some simulations under various structure settings, we found that a certain set of parameters well reproduced the Apollo seismic data, resulting in a new heterogeneous structure model of the Moon. The evaluated parameters were compared with those measured on the Earth and Mars, and we found that the Moon is more heterogeneous than others by about 10 times. This kind of comparison makes it easier to interpret the observed seismic signals on each solid body. Also, it is useful to explain the differences in their surface evolution scenarios. We believe that our results contribute to further extending comparative planetology. Key Points: Through full 3D seismic wave propagation simulation, we quantitatively evaluated the lunar seismic scattering propertiesWe found that a 10‐km thick scattering layer with 10% velocity fluctuation well‐reproduced the Apollo seismic observationOur results show that the upper lunar crust is about 10 times more heterogeneous than that of the Earth and Mars [ABSTRACT FROM AUTHOR]

In this study, systematic rock magnetic measurements and saturation isothermal remanent magnetization (SIRM) paleointensity calibration experiments were conducted for the returned samples from C‐type asteroid (162173) Ryugu and two carbonaceous chondrites (Orgueil and Tagish Lake) to evaluate the remanence carriers of the Ryugu sample and its ability as a paleomagnetic recorder. Our magnetic measurements show that Ryugu samples exhibit signatures for framboidal magnetite, coarse‐grained magnetite, and pyrrhotite, and that framboidal magnetite is the dominant remanence carrier of Ryugu samples in the middle‐coercivity range. The SIRM paleointensity constant was obtained for two Ryugu samples, and the median value was 3,318 ± 1,038 μT, which is close to the literature's value based on the average among magnetite, titanomagnetite, pyrrhotite, and FeNi alloys and is widely used for SIRM paleointensity experiments. The paleointensity values estimated using the obtained SIRM paleointensity constant indicate a strong magnetic field of the protoplanetary disk, suggesting that Sun's protoplanetary disk existed at the disk location of Ryugu's parent planetesimal when framboidal magnetite precipitated from the aqueous fluid. Plain Language Summary: Knowledge of rock magnetic properties is crucial to interpret a remanence record of sample and to reconstruct a reliable past magnetic field intensity value. Rock magnetic measurements and saturation isothermal remanent magnetization (SIRM) magnetic field intensity calibration experiments were conducted on returned samples from C‐type asteroid (162173) Ryugu and two meteorite samples (Orgueil and Tagish Lake) to evaluate the remanence carriers of the Ryugu sample and its ability as a past magnetic field recorder. Magnetic field intensity values estimated on the basis of newly obtained rock magnetic properties and SIRM magnetic field intensity constant indicate a strong magnetic field of the protoplanetary disk, suggesting that Sun's protoplanetary disk existed at the disk location of Ryugu's parent planetesimal when framboidal magnetite precipitated from the aqueous fluid. Key Points: Rock magnetic properties and paleointensity constant are investigated for returned samples from C‐type asteroid (162173) RyuguFramboidal magnetites dominate stable natural remanence components of Ryugu samples in a middle‐coercivity rangePaleointensity values estimated using our paleointensity constant indicate a strong magnetic field of the protoplanetary disk [ABSTRACT FROM AUTHOR]

Aim: Eating disorders (EDs) are complex, multifactorial psychiatric conditions. Previous studies identified pathogenic copy number variations associated with NDDs (NDD‐CNVs) in ED patients. However, no statistical evidence for an association between NDD‐CNVs and EDs has been demonstrated. Therefore, we examined whether NDD‐CNVs confer risk for EDs. Methods: Using array comparative genomic hybridization (aCGH), we conducted a high‐resolution CNV analysis of 71 severe female ED patients and 1045 female controls. According to the American College of Medical Genetics guidelines, we identified NDD‐CNVs or pathogenic/likely pathogenic CNVs in NDD‐linked loci. Gene set analysis was performed to examine the involvement of synaptic dysfunction in EDs. Clinical data were retrospectively examined for ED patients with NDD‐CNVs. Results: Of the samples analyzed with aCGH, 70 severe ED patients (98.6%) and 1036 controls (99.1%) passed our quality control filtering. We obtained 189 and 2539 rare CNVs from patients and controls, respectively. NDD‐CNVs were identified in 10.0% (7/70) of patients and 2.3% (24/1036) of controls. Statistical analysis revealed a significant association between NDD‐CNVs and EDs (odds ratio = 4.69, P = 0.0023). NDD‐CNVs in ED patients included 45,X and deletions at KATNAL2, DIP2A, PTPRT, RBFOX1, CNTN4, MACROD2, and FAM92B. Four of these genes were related to synaptic function. In gene set analysis, we observed a nominally significant enrichment of rare exonic CNVs in synaptic signaling in ED patients (odds ratio = 2.55, P = 0.0254). Conclusion: Our study provides the first preliminary evidence that NDD‐CNVs may confer risk for severe EDs. The pathophysiology may involve synaptic dysfunction. [ABSTRACT FROM AUTHOR]

Pre‐mRNA splicing imprints mRNAs by depositing multi‐protein complexes, termed exon junction complexes (EJCs). The EJC core consists of four proteins, eIF4AIII, MLN51, Y14 and Magoh. Magoh is a human homolog of Drosophila mago nashi protein, which is involved in oskar mRNA localization in Drosophila oocytes. Here we determined the effects of Magoh mutations equivalent to those of Drosophila mago nashi mutant proteins that cause mis‐localization of oskar mRNA. We found that Magoh I90T mutation caused mis‐localization of Magoh protein in the cytoplasm by reducing its binding activity to Y14. On the other hand, G18R mutation did not affect its binding to Y14, but this mutation reduced its association with spliced mRNAs. Our results strongly suggest that Magoh mutations equivalent to Drosophila mago nashi mutants cause improper EJC formation by reducing incorporation of Magoh into EJC. [ABSTRACT FROM AUTHOR]

Background and Aim: Balloon‐occluded retrograde transvenous obliteration (BRTO) is widely performed for treating gastric varices (GVs). However, worsening of esophageal varices (EVs) can be observed after BRTO. This study aimed to investigate the impact of EV worsening on prognosis after BRTO. Methods: Overall, 258 patients who underwent initial BRTO for GV treatment between January 2004 and May 2019 at 12 institutions were retrospectively registered. Results: Technical success was achieved in 235 patients (91.1%). Based on the exclusion criteria, 37 patients were excluded, and 198 were evaluated. The cumulative worsening rates of EVs at 1, 2, and 3 years were 39.0%, 59.4%, and 68.4%, respectively. In the univariate Cox proportional hazards model, sex, EV size, history of EV treatment, left gastric vein dilatation, platelet count, aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, albumin–bilirubin score, prothrombin time‐international normalized ratio, fibrosis‐4 index, AST to platelet ratio index, and spleen width were significantly associated with worsening of EV after BRTO. Multivariate analysis showed that sex (adjusted hazard ratio [aHR] 1.72; 95% confidence interval [CI] 1.03–2.86; P = 0.04), left gastric vein dilatation (aHR 1.90; 95% CI 1.17–3.10; P = 0.01), ALT (aHR 1.01; 95% CI 1.00–1.03; P = 0.02), albumin (aHR 0.61; 95% CI 0.43–0.87; P < 0.01), and spleen width (aHR 1.02; 95% CI 1.01–1.03; P < 0.01) were independent risk factors for worsening of EV after BRTO. Patients with EV worsening within 1 year after BRTO had a significantly worse prognosis than the other patients (P = 0.007). Conclusions: Early worsening of EV after BRTO was associated with poor prognosis after BRTO. [ABSTRACT FROM AUTHOR]

Asteroid 162173 Ryugu is a carbonaceous asteroid that was visited by Japan's Hayabusa2 spacecraft in 2018. The formation mechanism of the "spinning‐top" shape of Ryugu is a vital clue to the dynamical history of the near‐Earth asteroid. In this study, we address the long‐term evolution of its spin state induced by the Yarkovsky‐O'Keefe‐Radzievskii‐Paddack (YORP) effect, that is, the thermal recoil torque that changes the rotation period and spin‐pole direction. Given the current orbit, spin state, and three‐dimensional shape of Ryugu observed by Hayabusa2, we computed the YORP torque exerted on Ryugu using a simplified thermal model assuming zero thermal conductivity. Despite variations in the meter‐scaled topography, all 20 shape models that we examined indicate that the spin velocity of Ryugu is currently decreasing at a rate of (−6.3to−0.42)×10−6 $(-6.3\enspace \mathrm{to}\enspace -0.42)\times {10}^{-6}$ deg/day2. Our findings also suggest that the thermal torque is responsible for maintaining the spin pole upright with respect to the orbital plane. Therefore, the YORP effect may explain the significant spin‐down from an earlier period of 3.5 hr to the present period of 7.6 hr. The corresponding time scale of the spin‐down is estimated to be 0.58–8.7 million years, depending on the input shape models. This time scale is comparable to the formation period of the largest crater, Urashima (5–12 Ma), or the western bulge (2–9 Ma) as derived from previous studies on crater statistics in Ryugu. Thus, its rotation may have started to decelerate as a consequence of major resurfacing events. Plain Language Summary: The Japanese spacecraft Hayabusa2 visited the kilometer‐sized asteroid, Ryugu, and found it to have a spinning‐top shape with a diamond‐like cross‐section. For an aggregate of rock fragments to deform in this way, fast rotation is required. The current rotation period of Ryugu is 7.6 hr, and its rotational speed is not sufficiently fast to deform the entire body. It is proposed that Ryugu rapidly spun in the past and has since slowed down. Light has no mass, but it does have momentum and produces a faint pressure on the surface of the asteroid. As Ryugu is heated by the Sun, thermal radiation is emitted from its surface, resulting in a breaking effect and changing the rotational speed of the asteroid over millions of years. We found that the radiation pressure is a reasonable mechanism for the spin‐down of the asteroid and thus provides a clue to Ryugu's history. Key Points: Thermal recoil torque (i.e., the YORP effect) plays a dominant role in the spin‐down of asteroid 162173 RyuguThe estimated spin‐down time scale (0.58–8.7 million years) indicates a period of major change in the topography of RyuguThe YORP effect is responsible for keeping the spin‐pole of Ryugu perpendicular to the orbital plane [ABSTRACT FROM AUTHOR]

This 31‐parameter panel was developed for simultaneously measuring multiple immune cell populations including T cells, B cells, natural killer cells, dendritic cells, monocytes, and hematopoietic progenitor cells in human peripheral blood mononuclear cells. This panel enables the capture of individual immune dynamics and assessments of single‐cell changes in the immune system that are associated with aging and diseases. This panel includes markers to separate the differentiation status of each cell population and might be applicable to studies of infectious and autoimmune diseases, as patient samples are usually limited in volume and require an analysis system that provides a relatively large amount of information. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the imaging findings of pericoronal myxofibrous hyperplasia (PMH), especially panoramic radiography and multidetector computed tomography (MDCT). Materials and methods: In all, 13 patients with PMH who underwent panoramic radiography and MDCT were included in this study. For patients with PMH, interpretation with panoramic radiography and MDCT findings were independently analyzed by two oral and maxillofacial radiologists. Any discrepancies of the imaging evaluation were resolved by consensus of the two oral and maxillofacial radiologists. Results: Almost all cases with PMH were teenage (n = 11, 84.6%), women (n = 10, 76.9%), and maxilla (n = 9, 69.2%). Of all cases with PMH, the interpretation with panoramic radiography was as dentigerous cyst (n = 4, 30.8%) or unerupted tooth (n = 9, 69.2%). MDCT findings of all cases were expansive process around crown of impacted tooth. MDCT showed well‐defined unilocular lesion and spread of lesion to better advantage than panoramic radiography. Furthermore, the CT values of PMH were 13.9 ± 3.9 HU (range, 8.4‐22.0 HU). Conclusions: The results of the present study indicate the clinical and imaging features of PMH. We believe that PMH is often misdiagnosed because of the overlap of its histological features with other odontogenic cysts or unerupted tooth. [ABSTRACT FROM AUTHOR]

Anisotropic sintering, including shrinkage and grain growth, was examined for c‐axis‐oriented (Sr,Ca)2NaNb5O15 (SCNN) ceramics, which were prepared by colloidal processing under a magnetic field. In the c‐axis‐oriented SCNN powder compact, shrinkage and grain growth along the c‐axis were higher than those along the a‐axis. The anisotropic microstructural development was clearly associated with anisotropic sintering shrinkage. X‐ray diffraction, scanning electron microscopy, and energy back scattering diffraction showed that the grain growth of oriented particles by including random grains contribute to the development of the oriented microstructure. Finally, the highly crystal‐oriented SCNN ceramics with a densified microstructure were obtained through anisotropic sintering. These results clearly showed the potential to develop a well‐defined anisotropic microstructure during sintering by designing and controlling the particle packing structure in a powder compact. [ABSTRACT FROM AUTHOR]

Aim: Musculoskeletal degenerative disease (MSD; osteoporosis, knee arthritis and lumbar spondylosis) decreases the quality of life (QOL) of older people. The objective of the present study was to identify the factors related to the absence of MSD in multivariate logistic regression analysis. Methods: The participants were 1034 volunteers (444 men, 590 women, mean age 63.5 years) in the Yakumo study. Osteoporosis (percentage of young adult mean ≤70%), knee arthritis (Kellgren–Lawrence grade ≥2), and lumbar spondylosis (Nathan class ≥3) were prospectively examined. Participants were divided into those with and without MSD. Age, sex, body mass index, muscle strength, gait ability, pain, body balance, spinal sagittal alignment, geriatric syndrome (locomotive syndrome, frailty and sarcopenia) and QOL (Short Form Health Survey) were compared between these groups to identify the factors associated with the absence of MSD. Results: Significantly lower age, body mass index and pain; higher gait speed, grip and back muscle strength; more stable body balance; better sagittal spinal alignment; and lower rates of locomotive syndrome, frailty and sarcopenia were observed in the group without MSD (n = 445, 43%), with significantly better QOL (P < 0.0001). In multivariate logistic regression analysis adjusted for age and sex, lower body mass index (odds ratio [OR] 1.10, P < 0.001), lower spinal inclination (OR 1.08, P < 0.01), higher back muscle strength (OR 1.01, P < 0.05), no locomotive syndrome (OR 1.80, P < 0.05) and good body balance (OR: 1.12, P < 0.05) were significant factors for the absence of MSD. Conclusions: Factors related to an absence of MSD are also related to good QOL, and should be a focus of health interventions in healthy middle‐aged and older people. Geriatr Gerontol Int 2019; 19: 1141–1146. [ABSTRACT FROM AUTHOR]

Aim: To investigate the efficacy and safety of all‐oral direct‐acting antiviral treatments in patients coinfected with hepatitis C virus (HCV) and HIV. Methods: In all, 35 patients with HCV/HIV coinfection (22 patients with HCV genotype 1 infection, 6 with genotype 2, and 7 with genotype 3) were treated with sofosbuvir and ledipasvir (for genotype 1 patients) or sofosbuvir and ribavirin (for genotypes 2 and 3). Sustained virological response (SVR) at 24 weeks after end of treatment and adverse events were assessed. Results: The overall SVR rate was 91.4% (32/35). One patient with genotype 1 infection discontinued treatment on day 2 due to severe headache, which subsided after the cessation of medication; all other patients completed their treatment without severe adverse events. Two patients who had a relapse of HCV were infected with a genotype 3 strain. We observed hyperbilirubinemia in a patient with genotype 3, who was under antiretroviral therapy including atazanavir. He completed the treatment and achieved SVR. Conclusion: Direct‐acting antiviral treatment for patients coinfected with HCV/HIV is as effective as in patients infected only with HCV. It was generally well tolerated, except in one patient who discontinued the treatment due to severe headache. [ABSTRACT FROM AUTHOR]

Aim: Ongoing hepatitis A outbreaks among men who have sex with men (MSM) have been reported worldwide, mainly in Europe, since 2016. In Japan, there has been an increase in the number of notified hepatitis A cases since January 2018, most of which were suspected to have been transmitted through homosexual contact. In this paper, we describe the current outbreak situation of hepatitis A among MSM. Methods: Between March and July 2018, 13 cases of hepatitis A were identified in our hospital. All cases were identified as MSM. Data on clinical and laboratory findings and therapies were collected from medical records. Serum or stool samples were obtained from 13 patients and subjected to sequence analysis. Results: Of all patients, 12 reported to have male‐to‐male homosexual contact within 7 weeks prior to symptom onset, and 6 visited sex‐on‐premises venues in the same area. Furthermore, 12 patients were infected with HIV and consequently received antiretroviral therapy with sustained viral suppression. Ten patients received pulsed methylprednisolone therapy. Plasma exchange was additionally carried out in one patient. All patients received inpatient hospital care and were discharged alive. Sequence information, which was available in all cases, showed that the hepatitis A virus strain was identical to the EuroPride strain (RIVM‐HAV16–090). Conclusions: Results of sequence analysis suggest that the ongoing hepatitis A outbreak among MSM in Japan is linked to the 2016 European outbreaks. A vaccination program is urgently required for high‐risk populations to control this ongoing outbreak. [ABSTRACT FROM AUTHOR]

Spinal fusion and bone defects after injuries, removal of bone tumors, and infections require repair by implantation. In this study, we show self‐assembling peptide (SPG‐178) hydrogel‐induced bone healing in vivo. Posterolateral lumbar fusion and tibial intramedullary models of rabbits were prepared. In the tibia model, micro‐CT analysis revealed a significantly higher degree of newly formed bone matrix in the SPG‐178 group compared to the other groups. SEM/3D micrographs showed that the cavity filled with SPG‐178 had collagen fibers attached to host bone. After 28 days, samples from the SPG‐178 group showed significant repair of the defect. In the posterolateral lumbar fusion models, micro‐CT showed a tendency for a higher degree of newly formed bone matrix in the SPG‐178 group compared to the β‐TCP and bone chips only groups. Von Kossa staining showed marked new bone formation attached to the lamina that was most prominent at the implanted SPG‐178 composite margin. SPG‐178 is a material that is likely to be used in clinical applications because it has several benefits. These include its favorable bone conduction properties, its ability to act as a support for various cells and growth factors, its lack of infection risk compared with materials of animal origin such as ECM, and the ease with which it can be used to fill defects with complex shapes and be combined with a wide range of other materials. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3285–3293, 2018. SEM/3D micrographs of the tibia intramedullary model. At 7 days, collagen fibers and osteoblast proliferation were visible, especially in the cavity filled with SPG‐178. At 28 days, SPG‐178 samples showed significant restitution of the defect. Use of SPG‐178 seems to make it possible to maintain structure, even in bone defects, and to achieve good bone conduction. [ABSTRACT FROM AUTHOR]

The article presents a study on the mechanism of human and mouse skin mast cell activation by neuropeptide, neuromedin U (NMU). It discusses the characterization of NMU, an analysis of receptor proteins for NMU, the release of NMU from human keratinocytes, and the activation of connective tissue-type mast cells and human skin-derived mast cells by NMU.

Congenital absence of the portal vein (CAPV) is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. CAPV is classified into two types based on the absence (type I) or presence (type II) of portal venous flow into the hepatic parenchyma and is associated with multiple other anomalies such as usually benign hepatic tumors. There have been only two case reports describing hepatocellular carcinoma (HCC) in patients with CAPV type II to date. We report the third such patient. A 50‐year‐old woman was referred to our hospital for management of a giant hepatic tumor. Contrast‐enhanced computed tomography (CECT) indicated a huge mass occupying the right lobe of the liver; the radiological diagnosis was HCC. CECT also demonstrated that the superior mesenteric vein (SMV) and the splenic vein (SpV) joined to form a shunt draining into the left renal vein and that a hypoplastic portal vein branched from the confluence of the SMV and SpV and drained into the liver, indicating that the CAPV was type II. Liver resection was successfully performed to treat the HCC, and the pathological diagnosis was well‐differentiated HCC. Seven months after the operation, a recurrent small HCC was detected and treated with radiofrequency ablation without complications. The patient has been carefully followed for 6 months to date without any evidence of further recurrence. Patients with CAPV are predisposed to developing HCC and require close surveillance. [ABSTRACT FROM AUTHOR]

One of the most important goals of flat panel display (FPD) manufacturing is to reduce the cost of excimer laser annealing (ELA) processes of low-temperature poly-Si (LTPS) technology. We developed novel XeF (351 nm) and KrF (248 nm) excimer lasers specially designed for ELA. The semiconductor-field-proven excimer laser technologies are applied to stabilize the operation and to reduce the cost. [ABSTRACT FROM AUTHOR]

Sintering stress and bulk viscosity were derived as functions of relative density from microtomographic images in viscous sintering of glass particles. Three methods were proposed to estimate the sintering stress from relative density, specific surface area, and average of curvature on pore surface, which were directly measured by X-ray microtomography. The surface energy method gave valid value in the final stage of sintering, while the mixed method gave better estimation in the intermediate stage. For the initial stage of sintering, the sintering stress was calculated from the average contact radius and the average coordination number observed by X-ray microtomography. The sintering stress at the final stage increased in free sintering, but it decreased in constrained sintering due to pore coarsening. The bulk viscosity was calculated from the shrinkage rate and the sintering stress. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB-induced degranulation is accompanied by cytosolic Ca2+ mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca2+ chelator), raising the possibility that DNFB acts on the G protein-coupled receptors and activates Gi, which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure-activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation. [ABSTRACT FROM AUTHOR]

Aim Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's quality of life, leading to poor compliance with further treatments. Previous studies have provided minimal data about carboplatin-based regimens. Female sex is a known risk factor for CINV. The purpose of this study was to evaluate palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by carboplatin plus paclitaxel combination therapy (TC regimen) in patients with gynecologic cancers. Material and Methods Patients were recruited for this phase-II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX. Results During the overall period, complete response (CR) was observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was already present ( P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in the 1-day DEX arm tended to be lower than in the 3-day DEX arm. Conclusion Combination therapy of palonosetron and 1-day DEX was effective for subjects undergoing a TC regimen for gynecologic cancers. However, the possibility of reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could not be refuted and requires further investigation. [ABSTRACT FROM AUTHOR]

Aim CD26 is a membrane glycoprotein that has multiple functions, including dipeptidyl peptidase IV activity. CD26 expression varies in different tumor types, and its role in tumor growth in hepatocellular carcinoma ( HCC) remains unclear. Methods CD26 expression levels were examined in resected HCC and surrounding non-cancerous lesions. The effect of CD26 knockdown on the cellular proliferation of HepG2 or Huh7 cells, both of which highly express CD26, was studied in vitro. Results CD26 mRNA expression levels were significantly increased in HCC compared with their surrounding non-cancerous lesions. We confirmed that various HCC cell lines, especially HepG2 and Huh7 cells, showed high expression levels of CD26. siRNA-mediated knockdown of CD26 suppressed hepatoma cell growth in vitro. CD26 knockdown induced cell cycle arrest through the upregulation of Cip/Kip family proteins, p21 in HepG2 cells and p27 in Huh7 cells. CD26 knockdown did not affect apoptosis, but it increased expressions of the pro-apoptotic proteins Bim and Bak and the anti-apoptotic protein Bcl-xL, suggesting an addiction of CD26 knockdown cells to Bcl-xL for survival. We thus treated CD26 knockdown cells with ABT-737, a Bcl-xL/-2/-w inhibitor, and observed that the synthetic lethal interaction of combined Bcl-xL and CD26 inhibition induced significant apoptosis and impaired cellular viability. Conclusion CD26 mRNA was overexpressed in HCC, and its inhibition suppressed cellular proliferation through cell cycle arrest. The combined use of CD26 knockdown with a Bcl-xL inhibitor further elicited substantial apoptosis and therefore may serve as a powerful anticancer combination therapy against HCC. [ABSTRACT FROM AUTHOR]

The dispersed state of particles in high-concentration slurries has a significant effect on the development of the particle packing structure of the powder compact. We observed individual particle motion directly in highly concentrated ceramic slurries under slow flow through confocal laser scanning fluorescent microscopy using transparent slurries. In particular, we focused on particle motion soon after the application of a constant low shear rate. Measurements of the shear stresses indicated that the stress of a 30 vol% slurry gradually increased from 0.018 Pa over time, whereas the stress of a 40 vol% slurry soon reached 0.03 Pa and remained constant. For direct observation, shear stress was applied to the slurry, which was set between two glass plates, by moving one unilateral glass plate at 0.8 μm/s, to create a shear rate of 0.01 s−1. The motion of the particles could be observed continuously. In the early stage, particles in the 30 vol% slurry near the moving plate were united as one body and did not alternate positions. Then, a speed incline developed gradually over time. For the 40 vol% case, the particles moved at the same time and together. Increases in the shear stress were caused by increased interaction when the particles were close together. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine whether patterns of increases in serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels at birth were associated with the development of white matter injury (WMI) in preterm infants with a fetal inflammatory response (FIR). Methods: One hundred infants who were born at <32 weeks gestation and had funisitis, as determined by histological evidence of FIR, were studied. Infants were divided into four groups according to IL-6 and CRP levels at birth, with cut-off values of 200 pg/mL and 0.4 mg/dL, respectively. We compared the incidence of WMI, determined by MRI at term-equivalent age, among these groups. Results: The number of infants in each group was 12, 43, 0, and 45 in the high IL-6 and high CRP (HH) group, high IL-6 and low CRP (HL) group, low IL-6 and high CRP (LH) group, and low IL-6 and low CRP (LL) group, respectively. The incidence of WMI was significantly higher in the HH group than in the HL group and LL group (83%, 40%, and 34%, respectively). Multiple logistic regression analysis revealed that a combined elevation in IL-6 and CRP levels was an independent predictor for the development of WMI (odds ratio, 8.3). Conclusion: A combined elevation in serum IL-6 and CRP levels at birth was associated with the development of WMI in preterm infants with FIR. [ABSTRACT FROM AUTHOR]

Grain-oriented polycrystalline alumina (PCA) ceramics with very high, nearly single-crystal transparency were successfully fabricated through colloidal processing in a high magnetic field followed by hot isostatic pressing. The c-axis of the produced material was oriented along the direction parallel to the magnetic field. The transmittance of the specimen with a thickness of 0.8 mm was 78% at a wavelength of 650 nm, close to the reported value of 84.5% for sapphire and more than 10% higher than the largest transmittance magnitude ever reported for PCA ceramics. In addition, the Na salt of 4,5-dihydroxy-1,3-benzenedisulfonic acid (named "Tiron") was found to be a highly effective dispersant for processing high-purity materials. [ABSTRACT FROM AUTHOR]

Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase ( HDC). Previous studies have shown that Hdc−/− mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc−/− peritoneal mast cells. Impaired granule maturation was also found in Hdc−/− BM-derived cultured mast cells when they were cocultured with fibroblasts in the presence of c-kit ligand. Exogenous application of histamine and several H4 receptor agonists restored the granule maturation of Hdc−/− cultured mast cells. However, the maturation of granules was largely normal in Hrh4−/− peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter-2, did not affect granule maturation. In vivo experiments with mast cell deficient KitW/ KitW-v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator. [ABSTRACT FROM AUTHOR]

The crystallographic orientation of α- Al2 O3 powder compact under a magnetic field is affected by the presence of aggregates. In this work, the influence of aggregates on the orientation degree was studied from the experimental and theoretical viewpoints. The optical parameter of birefringence was used as an evaluation index for the crystallographic orientation of α- Al2 O3 compact samples. The effect of aggregates on the orientation degree was estimated from the simulation of the distribution of the relative angles between the crystal axes of primary particles for any constituting number of aggregates. The orientation of an aggregate depends on the apparent crystal axes calculated from the vector summation of the crystal axes for all constituting particles. The measured degree of orientation of the powder compact was consistent with the theoretical values for all powder compact samples containing various concentrations and constituting numbers of aggregates. The elimination of aggregates is the key for good particle alignment under a magnetic field. [ABSTRACT FROM AUTHOR]

We have developed a 'OleDry-F' transparent new liquid desiccant can be directly sealed by filling in the OLED panel. 'OleDry-F' is a new desiccant to remove the hydrocarbon solvent that is included in the 'OleDry' transparent liquid drying agent of the Company. In addition, the appearance of OleDry-F itself is transparent. This feature is obviously suitable for top emission type or see through type OLED. And also OleDry-F is able to adjust its viscosity to get a higher flexibility for mechanical design of OLED. From the result of this development, we think our new desiccant OleDry-F is also suitable for film type OLED. [ABSTRACT FROM AUTHOR]

The following article from Pediatrics International, 'Surfactant lavage therapy for respiratory deterioration in extremely premature infants' by Sota Iwatani, Masami Mizobuchi, Satoshi Tanaka, Kei Inomata, Hitomi Sakai, Seiji Yoshimoto and Hideto Nakao, posted online as an Accepted Article on 30 October 2012 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, the journal Editor in Chief, and Wiley Publishing Asia Pty. Ltd. The withdrawal has been agreed due to deficiencies in the study design. Reference [ABSTRACT FROM AUTHOR]

Der Gast bestimmt: Ein Porphyrinpolymer, poly(PorZn⋅DD) (siehe Bild, rosa/violett), mit einem Porphyrinatozink ‐ und einem Porphyrin ‐ Doppeldeckerkomplex als Wiederholungseinheit, wurde synthetisiert. Die Porphyrinatozinkkomplexe in ihm erkennen ein divalentes Amin (braun/rot), was eine intramolekulare Drehbewegung durch Rotation der Porphyrin ‐ Doppeldeckerkomplexe zur Folge hat und so zu einer Verkürzung und Kompaktierung des Polymers führt. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy of a municipality-led walking program under the Japanese public Long-Term Care Insurance Act to prevent mental decline. Design Randomized controlled trial. Setting The city of Takasaki. Participants One hundred fifty community members aged 72.0 ± 4.0 were randomly divided into intervention (n = 75) and control (n = 75) groups. Intervention A walking program was conducted once a week for 90 minutes for 3 months. The program encouraged participants to walk on a regular basis and to increase their steps per day gradually. The intervention was conducted in small groups of approximately six, so combined benefits of exercise and social interaction were expected. Measurements Cognitive function was evaluated focusing on nine tests in five domains: memory, executive function, word fluency, visuospatial abilities, and sustained attention. Quality of life ( QOL), depressive state, functional capacity, range of activities, and social network were assessed using questionnaires, and motor function was evaluated. Results Significant differences between the intervention and control groups were shown in word fluency related to frontal lobe function ( F(1, 128) = 6.833, P = .01), QOL ( F(1,128) = 9.751, P = .002), functional capacity including social interaction ( F(1,128) = 13.055, P < .001), and motor function (Timed Up and Go Test: F(1,127) = 10.117, P = .002). No significant differences were observed in other cognitive tests. Conclusion Walking programs may provide benefits in some aspects of cognition, QOL, and functional capacity including social interaction in elderly community members. This study could serve as the basis for implementation of a community-based intervention to prevent mental decline. [ABSTRACT FROM AUTHOR]

Abstract: A hypomorphic mutation of the gene encoding zeta-associated protein-70 (ZAP-70), a signaling molecule in T cells, produces autoimmune arthritis in mice under a microbially conventional condition but not in a clean environment. The genetic anomaly alters thymic selection of self-reactive T cells as well as natural regulatory T cells and their respective functions. Highly self-reactive polyclonal T cells, including arthritogenic ones, thus produced by the thymus strongly recognize self-antigens presented by antigen-presenting cells, stimulate them to up-regulate co-stimulatory molecules and secrete cytokines that drive naïve self-reactive T cells to differentiate into autoimmune effector Th17 cells. Administration of microbial products and activation of complement can facilitate the differentiation, evoking clinically overt arthritis in a microbially clean environment. Furthermore, mutation-dependent graded attenuation of T cell receptor signaling alters disease phenotypes and the dependency of disease occurrence on the environment. These findings provide a model of how genetic and environmental factors, in association, cause autoimmune diseases such as rheumatoid arthritis. [Copyright &y& Elsevier]

Aim: To assess the maternal and neonatal outcomes of pregnant women with mental disorders in Japan. Material and Methods: We conducted this retrospective cohort study to examine the patients who delivered at Nagoya University Hospital (2005-2009). Thereafter, the patients without any complications other than mental disorders and with several sources of psychiatric information were included in the present series, and the maternal and neonatal outcomes between patients with or without maternal mental disorders were compared. The psychiatric outcomes and the adverse effects of psychotropic drugs were also examined. Results: A total of 1649 women delivered during this period, and 63 of them were complicated by maternal mental disorders. After the selection of patients for comparison purposes, women with mental disorders ( n = 51) had a slightly but significantly shorter gestational age (39.2 ± 0.2 vs 39.8 ± 0.1 weeks, P = 0.003) and smaller birth weight (2993.0 ± 56.7 vs 3152.4 ± 23.6 g, P = 0.010) compared with the control group ( n = 278). Intervention by psychiatrists was required for only 10 patients, and no patients required termination of pregnancy due to exacerbation of mental disorders. In schizophrenia patients who were taking atypical antipsychotics and benzodiazepine, a significant increase in maternal gestational weight gain, and a significant shorter gestational age were detected, respectively, compared with patients who were not receiving any drug treatments. Conclusion: A trend towards a lower birth weight and shorter gestational age was observed in Japanese women with well-controlled mental disorders, but the effect of well-controlled mental disorders on the perinatal outcome was minimal. [ABSTRACT FROM AUTHOR]

Compatibility of poly(vinyl butyral) (PVB) to mixed organic solvents of xylene and isopropyl alcohol (IPA) was studied viscometrically in alumina slurry, and the influence on the structure of green sheets was examined by a confocal laser scanning microscopy. The PVB molecule had both butyral (hydrophobic) group and hydroxyl (hydrophilic) group. The various mixed solvents including xylene and IPA were prepared by changing the each concentration. The intrinsic viscosity of a PVB molecule in a mixed organic solvent was higher than that in the plain solvent. The homogeneous green sheets were obtained from their slurries with mixed solvents. The high intrinsic viscosity indicated the expanded conformation of the PVB molecule in the mixed solvents. The results showed that the expanded conformation of the PVB molecule in the solvents was effective for dispersion of alumina particles. The control of the compatibility of the PVB molecule and the mixed organic solvents was an important factor for fabricating the homogeneous green sheets. [ABSTRACT FROM AUTHOR]

The high electrical conductivity, 1150 S/cm at room temperature, in the ab-plane of c-axis textured Al-doped ZnO is attributed to its high Hall mobility that is almost double the mobility in the c-axis direction. Temperature-independent mobility in the ab-plane below 200 K suggests that ionized impurity dominates the scattering of electron transport, which reasonably agrees with a modified Brooks-Herring-Dingle model taking into account nonparabolic E- k dispersion. However, the pronounced anisotropy between ab-plane and c-axis cannot be expected based on the model. Detailed observations of the grain boundary (GB) by means of high-resolution transmission electron microscopy, high-angle annular dark-field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy revealed the existence of an Al-enriched, Zn-deficient layer near the GB traversing the c-axis direction. In contrast, the highly conductive direction encompasses a tilt grain boundary, in which coincident sites were observed and Al segregation was barely evident. We conclude that such a preferential segregation in the GB and/or GB structure itself are responsible for the anisotropy of mobility in the textured Al-doped ZnO. [ABSTRACT FROM AUTHOR]

Embryonic stem cells (ESCs) have a distinctive epigenome, which includes their genome-wide DNA methylation modification status, as represented by the ESC-specific hypomethylation of tissue-dependent and differentially methylated regions (T-DMRs) of Pou5f1 and Nanog. Here, we conducted a genome-wide investigation of sequence characteristics associated with T-DMRs that were differentially methylated between ESCs and somatic cells, by focusing on transposable elements including short interspersed elements (SINEs), long interspersed elements (LINEs) and long terminal repeats (LTRs). We found that hypomethylated T-DMRs were predominantly present in SINE-rich/LINE-poor genomic loci. The enrichment for SINEs spread over 300 kb in cis and there existed SINE-rich genomic domains spreading continuously over 1 Mb, which contained multiple hypomethylated T-DMRs. The characterization of sequence information showed that the enriched SINEs were relatively CpG rich and belonged to specific subfamilies. A subset of the enriched SINEs were hypomethylated T-DMRs in ESCs at Dppa3 gene locus, although SINEs are overall methylated in both ESCs and the liver. In conclusion, we propose that SINE enrichment is the genomic property of regions harboring hypomethylated T-DMRs in ESCs, which is a novel aspect of the ESC-specific epigenomic information. [ABSTRACT FROM AUTHOR]

DNA methylation profile, consisting of tissue-dependent and differentially methylated regions (T-DMRs), has elucidated tissue-specific gene function in mouse tissues. Here, we identified and profiled thousands of T-DMRs in embryonic stem cells (ESCs), embryonic germ cells (EGCs) and induced pluripotent stem cells (iPSCs). T-DMRs of ESCs compared with somatic tissues well illustrated gene function of ESCs, by hypomethylation at genes associated with CpG islands and nuclear events including transcriptional regulation network of ESCs, and by hypermethylation at genes for tissue-specific function. These T-DMRs in EGCs and iPSCs showed DNA methylation similar to ESCs. iPSCs, however, showed hypomethylation at a considerable number of T-DMRs that were hypermethylated in ESCs, suggesting existence of traceable progenitor epigenetic information. Thus, DNA methylation profile of T-DMRs contributes to the mechanism of pluripotency, and can be a feasible solution for identification and evaluation of the pluripotent cells. [ABSTRACT FROM AUTHOR]

Most conceptuses derived by somatic cell nuclear transfer (SCNT) in mice undergo developmental arrest as a result of embryonic or extraembryonic defects. Even when fetuses survive to term, prominent placental overgrowth or placentomegaly is often present, indicating that SCNT affects the development of trophoblast cell lineage. The trophoblast cell lineage is established at the blastocyst stage when the stem cell population of the trophoblast cell lineage resides in the polar trophectoderm. Therefore, it is possible that the developmental arrest and placentomegaly that accompany SCNT are induced by insufficient reprogramming of the donor somatic nucleus to enable the cells to acquire full potency as stem cells of the trophoblast cell lineage. Despite the abnormalities of the extraembryonic tissues of SCNT embryos, trophoblast stem (TS) cell lines have been successfully isolated from SCNT blastocysts and their properties appear to be indistinguishable from those of TS cells derived from native blastocysts. This suggests that SCNT does not affect the emergence and autonomous properties of TS cells. In this review, we discuss specification of cell lineage and the extent of reprogramming of TS cells in SCNT blastocysts. [ABSTRACT FROM AUTHOR]

Aims: Rest–activity rhythms of human beings generally synchronize to a 24-h time cue. Very few detailed research studies have examined rest–activity rhythms in patients with schizophrenia. The present study aimed to explore (i) rest–activity rhythms in patients with schizophrenia, and (ii) factors relevant to their rhythm characteristics. Methods: We selected only inpatients for this research, because the time cue for inpatients was considered more standardized than that of outpatients. Sixteen inpatients with schizophrenia wore an ActiTrac accelerometer-based activity monitor (IM Systems Inc., Baltimore, USA) for eight consecutive days to measure their activity. We used a χ2 periodogram to compute rest–activity rhythms from the activity data, whereby the χ2 value amplitude was regarded as an index of regularity. We conducted non-parametric tests to identify factors relevant to rhythm cycles and patterns. Results: Half of the participants exhibited prolonged rest–activity cycles, and 25% also had irregular rest–activity patterns defined by insufficient χ2 value amplitude, even though they were clearly under a 24-h time cue. Participants with misaligned rest–activity rhythms had attended daytime non-medical treatment programs less frequently, and had received more anti-anxiety/hypnotic medications than those with proper rhythms. Conclusion: Changes in rest–activity rhythms by optimizing pharmacological and non-pharmacological treatment could improve social adjustment or quality of life in patients with schizophrenia. [ABSTRACT FROM AUTHOR]