Search

Background: This study evaluated the chronological changes in physical and cognitive functions in middle-aged and older adults with and without rheumatoid arthritis (RA).Methods: This population-based case-control longitudinal study included individuals aged 40–79 years at baseline who agreed to participate. We identified 42 participants with RA and randomly selected 84 age- and sex-matched controls. Physical function was assessed according to gait speed, grip strength, and skeletal muscle mass. Cognitive function was assessed based on the information, similarities, picture completion, and digit symbol substitution test scores of the Wechsler Adult Intelligence Scale-Revised Short Form. The general linear mixed models comprised the fixed effects of the intercept, case, age, time in years since baseline, and case×time interaction, which were used to examine longitudinal changes in physical and cognitive functions.Results: Regardless of RA status, grip strength decreased and the picture completion score increased in the group aged

Background: Among oral hypoglycemic agents (OHAs), imeglimin (Twymeeg) would be in focus. Case Presentation: The patient in this case is a 58-year-old female with a history of obesity and previous operations for posterior longitudinal ligament ossification. In early September 2022, she developed dizziness and a general feeling of unwellness, leading to a diagnosis of Type 2 Diabetes (T2D) with an HbA1c level of 11.1%. Result: The patient was treated with a low carbohydrate diet (LCD) and Twymeeg, resulting in a significant decrease in HbA1c levels from 11.1% to 9.0%, 6.7%, and 5.9% over the course of three months. Pre-prandial and post-prandial blood glucose levels were measured with great accuracy. Discussion and Conclusion: The administration of Twymeeg was found to be effective in reducing the patient’s HbA1c levels, and the relationship between HbA1c and glucose variability could be further investigated based on these results.

The iBNCT project aims to develop “iBNCT001,” a demonstration device of the linac-based neutron irradiation facility for boron neutron capture therapy (BNCT) application. iBNCT001 generates an epithermal neutron beam by irradiating 8 MeV protons accelerated by a linac onto a beryllium target. Currently, the linac can drive an average proton current of 2.1 mA. Several experiments were performed using a water phantom to confirm the main physical characteristics of the neutron beam produced at the irradiation position. The measurement results demonstrated that the maximum thermal neutron flux achievable in the phantom volume was approximately 1.36 × 10 9 cm − 2 s − 1 when a normal beam collimator with a 120 mm diameter was used. This neutron beam intensity was sufficient to complete the irradiation within 30 min using the BNCT approach. In addition to normal beam collimators, extended collimators that protrude 100 mm from the wall were developed. By using an extended collimator, it is possible to prevent interference of the patient’s body with the wall when irradiating head and neck cancers. The measurement results for the extended collimator demonstrated that irradiation with the collimator could be completed within 1 h when the neutron beam is generated with an average proton current of 2.1 mA.

Background: There is a limit to improving the characteristics of zirconia with only one kind of stabilizing element such as yttrium. The purpose of this study is to systematically evaluate the effects of various co-doped elements on mechanical and optical properties and to develop a novel composition of zirconia with enough properties to apply to dental restorations. Methods: Forty-four kinds of zirconia were prepared by combining trivalent cations yttrium (Y) and ytterbium (Yb), and pentavalent cations niobium (Nb) and tantalum (Ta) oxide as stabilizers. The combined contents ranged from 0 to 5.6 mol% for Y2O3, 0 to 4.2 mol% for Yb2O3, 0 to 1.5 mol% for Nb2O5, and 0 and 1.2 mol% for Ta2O5. These specimens were determined for fracture toughness and opacity. X-ray diffraction studies were undertaken to evaluate the microstructural change. Results: The present study revealed that adding of the trivalent cations Y and Yb reduced fracture toughness and opacity, whereas the addition of pentavalent cations Nb and Ta to zirconia stabilized with trivalent cations increased both properties. There was no clear difference in the effects of Y and Yb, Nb, and Ta. Conclusions: Considering many factors, the following composition is optimal: 3–4.2 mol% Y2O3 and/or Yb2O3 stabilized zirconia with up to 1.5 mol% Nb2O5 has sufficiently high fracture toughness values and sufficiently high translucency suitable for dental restorations.

We propose a water pump that actively transports water molecules through nanochannels. Spatially asymmetric thermal fluctuations imposed on the channel radius cause unidirectional water flow without osmotic pressure, which can be attributed to hysteresis in the cyclic transition between the wetting/drying states. We show that the water transport depends on fluctuations, such as white, Brownian, and pink noises. Because of the high-frequency components in white noise, fast switching of open and close states inhibits channel wetting. Conversely, pink and Brownian noises generate high-pass filtered net flow. Brownian fluctuation leads to a faster water transport rate, whereas pink noise has a higher capability to overcome osmotic pressure in the opposite direction. A trade-off relationship exists between the resonant frequency of the fluctuation and the flow amplification. The proposed pump can be considered as an analogy for the reversed Carnot cycle, which is the upper limit on the energy conversion efficiency.

Female cancer survivors planning to become pregnant are concerned about the impact of cancer treatment on their ability to maintain normal pregnancy and the negative impact on their offspring. However, studies on the pregnancy outcomes of cancer survivors in Japan are limited. Therefore, this study aimed to investigate the pregnancy outcomes of female cancer survivors by comparing them with women without a history of malignant tumors in Japan.This cross-sectional study included 3308 subjects, based on an internet-based questionnaire (self-reported) survey conducted in Japan. Differences in pregnancy outcomes, including multiple pregnancies, stillbirth, preterm birth (PTB), and infant birthweight, between cancer survivors and subjects without a history of malignant tumors, were evaluated using a generalized linear mixed-effects model with adjustment for possible confounding factors.Of 3308 subjects included in this study, 629 (19.0%) were cancer survivors, among whom cervical (40.4%), breast (19.1%), and thyroid (7.0%) malignancies were most frequent. 71 (2.2%) and 53 (1.6%) participants had a history of multiple pregnancies and stillbirth, respectively; 385 (11.8%), 179 (5.5%), and 137 (4.2%) participants, respectively, had histories of PTB at less than 37, 34, and 32 weeks of gestation. Further, 302 (10.7%), 326 (11.6%), and 330 (11.7%) participants delivered to low birthweight (LBW), small-for-gestational-age (SGA), and large-for-gestational-age (LGA) infants, respectively. Subjects with a history of cervical or breast cancers had significantly higher odds of PTB at37 weeks of gestation (adjusted odds ratios [ORs], 1.87 [95% CI: 1.25-2.81] and 2.61 [95% CI: 1.77-3.86], respectively), preterm LBW infants (adjusted ORs, 2.70 [95% CI: 1.39-5.24] and 2.76 [95% CI: 1.03-7.38], respectively), and LGA infants (1.98 [95% CI: 1.36-2.89] and 1.99 [95% CI: 1.14-3.49], respectively), compared to those without a history of a malignant tumor. Subjects with a history of thyroid cancer had significantly higher odds of stillbirth (adjusted OR, 5.11 [95% CI: 1.11-23.5]).Cancer survivors had a higher risk of adverse pregnancy outcomes than those without a history of malignant tumors in Japan. Healthcare providers should consider the high likelihood of adverse pregnancy outcomes during preconception counseling for cancer survivors.

This study was the first to determine the effectiveness of radon concentration measurement in water using the degassing method as a screening method based on the liquid scintillation counter method. The degassing method used two radon monitors (AlphaGUARD and RAD7) and two monitor-attached degassing devices (AquaKIT and RAD H2O). These were effective screening methods based on the WHO guideline value of 100 Bq L−1. The screening values confirmed that a combination of the AlphaGUARD and AquaKIT was preferred. The results are useful for radon measurement for exposure control in drinking water and environmental in-situ field measurement.

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI), inhibits multiple kinase pathways and is a promising anti-tumor agent for various solid tumors, including lung cancer. Herein, we report a patient with coexisting epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). The patient received afatinib for a postoperative intrapulmonary recurrence of lung adenocarcinoma harboring EGFR exon 19 deletion. Tumor reduction was achieved with afatinib; however, dose reduction was required because of grade 2 diarrhea and skin toxicity. The reduced dose maintained a partial response. Thirty-one months after introduction of afatinib, he was diagnosed as having BCR-ABL1-positive CML and nilotinib was added to his treatment regimen. However, the combination of nilotinib and afatinib aggravated his diarrhea, prompting discontinuation of afatinib. Because nilotinib does not have sufficient anti-tumor efficacy for CML, dasatinib was substituted for nilotinib. Thirty-five months after introduction of dasatinib, bosutinib was substituted for dasatinib because of uncontrollable pleural effusions. Dasatinib achieved 31- and 35-month progression-free survivals for CML and EGFR-mutant lung adenocarcinoma, respectively. Dasatinib is thus a therapeutic option for coexisting EGFR-mutant lung adenocarcinoma and BCR-ABL1-positive CML when TKI combination therapy is contraindicated by severe adverse events. In our patient, adding nilotinib to afatinib led to severe diarrhea. When administering TKI combination therapy, drug-drug interactions should be considered.

The 2017 clinical guidelines for obstetrical practice by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists were revised and published as the 2020 edition (in Japanese). The aim of these guidelines is to present appropriate standard obstetric diagnosis and management procedures that have reached consensus among Japanese obstetricians. The 2020 guidelines include 113 clinical questions and an appendix, followed by answers (CQA; originally 112 in the 2017 edition), a discussion, list of references, and some tables and figures presenting common problems and questions encountered in obstetrical practice. Each answer comes with a recommendation level of A, B, or C and has been prepared based principally on evidence or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 113 CQAs and the appendix are presented here to promote a better understanding of the current standard care practices for pregnant and lactating women in Japan.

A tractor-based robot with the capability of real-time assessing and visualizing the radioactive material density and fertility distribution of farmlands has been developed to accelerate the recovery process of the farmlands suffered by the accident of the Fukushima Daiichi Nuclear Power Plant (FDNPP). In a field test at a decontaminated farmland near FDNPP, within-field heterogeneities of soil contamination and fertility are clarified almost in real-time. Results obtained by this robot are consistent with the map by the conventional soil sampling or the history of decontamination activities.

1. Facing the bushmeat crisis, tropical forests require effective monitoring for sustainable wildlife management. To gain credibility with local people and conservation officials, the monitoring needs indicators that comply with local knowledge and predict the available faunal resources. 2. This study explores predictive indicators for bushmeat biomass --the total biomass of five main hunted mammals-- in a Cameroonian rainforest. We employed camera trapping and the Random Encounter and Staying Time (REST) model to estimate the spatial variation in each species' population density and bushmeat biomass at three sites. We then calculated six indicators from camera-trap capture rate estimates and assessed their predictive performance for the total wild meat amount. 3. Duikers generally increased with distance from the public road, but two red duiker species were more markedly affected by the distance than blue duikers. Spatial density patterns of brush-tailed porcupines and Emin's pouched rats differed between sites. Consequently, bushmeat biomass displayed exponential growth away from the road with varying degrees among the sites. 4. Of the six indicators, the R/B ratio (red-to-blue duiker ratio) and the D/R ratio (duiker-to-rodent ratio) exhibited positive linear-like correlations to bushmeat biomass at all sites. The correlation lines were moderately similar across sites in the R/B ratio but largely different in the D/R ratio, suggesting that the latter is unsuitable for sharing information between neighbouring communities. 5. Synthesis and applications. The two indicators based on captured animal composition may effectively predict the total biomass of the main target species for bushmeat hunting, given a reasonably large sample size. The R/B ratio (red duikers/blue duikers) is recommended as a first choice; the D/R ratio (duikers/rodents) can be a good alternative when information sharing is not essential. Because local hunters are aware of depletion-related changes in species composition of caught animals, these indices may be effectively incorporated into community-based wildlife monitoring., 1. Face à la crise de la viande de brousse, les forêts tropicales nécessitent un système de suivi efficace pour une gestion durable de la faune. Pour gagner en crédibilité auprès des populations locales et des responsables de la conservation, le suivi a besoin d'indicateurs qui respectent les connaissances locales et prédisent les ressources fauniques disponibles. 2. Cette étude explore des indicateurs prédictifs de la biomasse de la viande de brousse --la biomasse totale de cinq principaux mammifères chassés-- dans une forêt tropicale camerounaise. Nous avons utilisé des caméra-piège et le modèle REST (Random Encounter and Staying Time) pour estimer la variation spatiale de la densité de chaque espèce et de la biomasse de viande de brousse sur trois sites. Nous avons ensuite calculé six indicateurs à partir des estimations du taux de capture par caméra-piège et évalué leur performance prédictive pour la quantité totale de viande sauvage. 3. Le nombre de céphalophes augmentaient généralement avec la distance de la route publique, mais deux espèces de céphalophes roux étaient plus fortement affectés par la distance que les céphalophes bleus. Les modèles de densité spatiale des porcs-épics et des rats géants d'Emin différaient selon les sites. Par conséquent, la biomasse de viande de brousse a affiché une croissance exponentielle en s'éloignant de la route, avec des degrés variables selon les sites. 4. Parmi les six indicateurs, le ratio R/B (le ratio des céphalophes rouges par rapport aux céphalophes bleus) et le ratio D/R (le ratio des céphalophes par rapport aux rongeurs) présentaient des corrélations linéaires avec la biomasse de viande de brousse sur tous les sites. Les lignes de corrélation étaient modérément similaires d'un site à l'autre pour le ratio R/B mais largement différentes pour le ratio D/R, ce qui suggère que ce dernier n'est pas approprié pour le partage d'informations entre communautés adjacentes. 5. Synthèse et applications. Les deux indicateurs basés sur la composition des animaux capturés peuvent prédire efficacement la biomasse totale des principales espèces cibles de la chasse à la viande de brousse, à condition de disposer d'une taille d'échantillon raisonnablement importante. Le ratio R/B (les céphalophes rouges/bleus) est recommandé comme premier choix; le ratio D/R (les céphalophes/les rongeurs) peut être une bonne alternative lorsque le partage des informations n'est pas essentiel. Comme les chasseurs locaux sont conscients des changements liés à l'épuisement dans la composition des espèces des animaux capturés, ces indicateurs peuvent être efficacement intégrés dans le suivi communautaire de la faune., アフリカ熱帯雨林における野生動物資源量推定の有効な指標を発見 --地域住民主体の野生動物モニタリング法の基礎を確立--. 京都大学プレスリリース. 2022-08-26., Cameras candidly capture bushmeat mammals to avert crisis. 京都大学プレスリリース. 2022-08-30.

We have incorporated Evolution Strategies into the Replica-Exchange Monte Carlo simulation method to predict the phase behavior of several example fluids. The replica-exchange method allows one system to exchange temperatures with its neighbors to search for the most stable structure relatively efficiently in a single simulation. However, if the temperature intervals of the replicas are not positioned carefully, there is an issue that local exchange does not occur. Our results for a simple Lennard-Jones fluid and the liquid-crystal Yukawa model demonstrate the utility of the approach when compared to conventional methods. When Evolution Strategies were applied to the Replica-Exchange Monte Carlo simulation, the problem of a significant localized decrease in exchange probability near the phase transition was avoided. By obtaining the optimal temperature intervals, the system efficiently traverses a broader parameter space with a small number of replicas. This is equivalent to accelerating molecular simulations with limited computational resources and can be useful when attempting to predict the phase behavior of complex systems.

Purpose There is a great interest in developing eco-friendly operations as alternative uses of resources in the university campus, making the employment of technologies more sustainable. Practices such as energy management and efficiency initiatives have been encouraged to meet these sustainability goals. The purpose of this paper is to describe and discuss the main features of the GENIIOT project, a system of energy management using Internet of Things applied in a Brazilian university campus to support energy education practices and to promote lasting energy efficiency measures. The focus of the study is directed at the energy consumption of the air-conditioning system, which is responsible for 40% of the total electricity consumption. In addition, this project also scrutinizes processes such as the building occupants’ comfort demands, lighting levels and energy waste control. Design/methodology/approach A case study at the Unicamp campus was conducted to illustrate the design procedures through qualitative description. This study comprises an overview of the physical plant, hardware and software development, energy data monitoring, management process and energy education. Findings The GENIIOT project enables energy efficiency actions by concerning the use of air-conditioning equipment based on monitored data, different types of monitored rooms, user’s behaviors and their feedback. This initiative requires the engagement, awareness and actions from users combined with investment in energy efficiency to achieve an efficient use of this type of equipment. The proposed approach can be applied in the future to similar situations, inside the Unicamp campus and at other university campuses. In addition, this project can contribute to building efficiency analysis by using the hardware structure developed to monitor facilities and carry out evaluations, providing valuable information for strategic initiatives in energy efficiency projects and research and development programs based on practical experience and promoting a discussion about sustainability aspects in the context of the university campus for energy efficiency. Originality/value The GENIIOT project is aligned with some of the sustainable development goals, among which sustainability and responsible consumption are identified. Considering the sustainability issues, the economic dimension can be evaluated through a cost–benefit analysis of energy efficiency projects with prudent investment, while the social attractiveness of the project is ensured by education and awareness practices for the community that interacts with the system and learns about a more efficient way of using resources in the campus. Furthermore, there is a more conscious use of natural resources by minimizing waste from the use of electricity and reducing carbon dioxide emissions. GENIIOT is part of Sustainable Campus Project, a living laboratory which aims at developing energy-efficiency-related research activities in the university campus to reduce costs in higher and federal institutions of education in Brazil.

For many mammal species, converting dung density into population density requires accurate estimates of defaecation rate and dung survival time. The latter parameter probably varies seasonally. In Nki National Park, south-east Cameroon, we monitored 216 dung piles of the blue duiker Philantomba monticola and 373 of the red duiker group (Cephalophus spp.), major game animals in Central Africa, and estimated dung survival time across seasons. Mean survival time was 6.83 days in the major dry season and 1.21–1.81 in other seasons for the blue duiker, and 7.37 and 1.53–4.05 for red duikers, lower than the values conventionally used for density estimations in Central Africa (i.e. 18 days for the blue duiker and 21 days for red duikers). Overall, beetles removed half of the dung within 1 day of deposition. However, the proportion of dung piles that beetles removed was significantly lower in the major dry season, and other dung piles remained longer until they disappeared as a result of other factors. As shorter dung survival time results in higher estimates of population density, our findings imply that in forests with intense beetle activity, duiker densities are higher than those based on the conventional values of dung survival time. Duiker densities and dung survival time should be estimated simultaneously. To minimize the bias introduced by rapid removal of fresh dung by beetles, only fresh dung (< 3 hours old) should be monitored when estimating mean dung survival time.

Immigration can have indirect negative effects, such as the additional burden of providing education to immigrant children who may need more support than native children to master the culture, customs, and language of the host country. This also leads to a transition of labor from the consumption sector to the education sector and a change in the number of children through the costs of education. Thus, using an overlapping generation model, we examine the effects of immigration on the welfare of the native population with the burden of providing schooling to native and immigrant children with endogenous fertility rates and endogenous unemployment rates. The results indicate that immigration may improve the welfare of the native population when the number of educators required for immigrant children is sufficiently low. Moreover, whether immigration improves the welfare of the native population depends not on the productivity of immigrants but on the increment in the number of educators caused by immigration.

Objective To investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA) Methods We performed post-hoc analyses of the ORIGAMI study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration ( Results SDAI scores decreased from baseline in all groups. SDAI scores trended to decrease more in the ACPA-positive group and disease duration Conclusion These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

Current technologies for ambient assisted living leave underexploited that social interaction is key to human wellbeing. Me-to-we design provides a blueprint for enriching such welfare technologies with social interaction. We present the five stages of me-to-we design, illustrate how it may transform a common class of welfare technologies, and discuss the distinguishing features of me-to-we design. These features include scaffolding social interaction around an activity and supporting transitions among the five stages. In contrast, most current welfare technologies support only some of the five stages and, thereby, either bypass social interaction or presuppose that social relations already exist. Me-to-we design offers a blueprint for building social relations stage by stage if they do not exist up front. It is for future work to validate whether the blueprint in practice delivers welfare technologies that are enriched by its profoundly sociotechnical approach.

Background Aortogenic embolism is one of the causes of embolic stroke of undetermined source, which can be difficult to diagnose. Methods We present the case of a 74‐year‐old male patient with a history of Bentall surgery and thoracic endovascular aortic repair who was transported to our hospital with sudden‐onset right‐sided hemiplegia and total aphasia. Magnetic resonance imaging revealed an acute left middle cerebral artery occlusion. Subsequently, an emergency mechanical thrombectomy was performed, through which the left middle cerebral artery was partially reperfused. We immediately investigated the aorta using an angioscopy. Results The angioscopy revealed a thrombus attached to an artificial blood vessel of the aorta close to the origin of the left common carotid artery. Because no other source of the embolus could be identified using electrocardiography or ultrasound, we diagnosed an aortogenic cerebral infarction by combining these findings with the pathological findings of the collected thrombus. Conclusions This is the first report that aortogenic cerebral infarction could be diagnosed using an angioscopy immediately after a cerebral artery thrombectomy.

Background Maintaining oral health is essential for improving overall health of children living with HIV. Therefore, we evaluated the effectiveness of an oral health intervention for improving their oral and overall health. In addition, we examined their longitudinal association between changes in oral and overall health. Methods We conducted a 2-year randomized controlled trial involving children living with HIV in Cambodia. Children aged 3–15 years and their caregivers were randomly allocated either to the intervention (group A) or control (group B) arm. A second control arm (group C) included children without HIV. The group A children received oral health education sessions and practiced home-based daily care. Results In the baseline survey, 482 children participated (group A: n = 160, group B: n = 168, group C: n = 154), and 350 completed the endline survey. An interaction effect in teeth brushing duration was observed in children in group A relative to group B (AOR = 2.69, 95% CI: 1.37–5.31) and group C (AOR = 3.78, 95% CI: 1.70–8.40). Longitudinal associations were observed between changes in oral hygiene and overall health, as presented by alterations in dental caries in permanent teeth with viral load detection (adjusted odds ratio = 3.58, 95% CI: 1.10 − 11.73), in salivary flow quantity with the overall quality of life (β = 0.07, 95% CI: Conclusions Oral health intervention may improve oral care behaviors and potentially enhance overall health among children living with HIV in antiretroviral therapy in a resource-constrained setting. Trial registration ISRCTN 15177479.

This literature review aimed to evaluate the effectiveness of rituximab (RTX) in patients with systemic sclerosis (SSc). PubMed was searched for articles, published through 31 March 2022, on any controlled studies using RTX in the treatment of SSc. Of 85 identified articles, 9 were selected by title/abstract screening and full text examination. All nine articles reported outcomes of forced vital capacity (%FVC), and seven reported those of modified Rodnan skin scores (mRSS). The results showed that among the seven controlled studies evaluating skin lesions in patients with SSc, four showed a significant improvement of mRSS by RTX when compared with a control group, whereas three showed no significant effect. Among the nine controlled studies evaluating lung lesions, five showed a significant improvement of %FVC compared with a control group, whereas four showed no significant effect. In conclusion, RTX may be effective in the treatment of skin and lung lesions in patients with SSc. The profiles of SSc patients for whom RTX was indicated were unclear, although patients with diffuse cutaneous SSc and those positive for anti-topoisomerase I antibody were considered potential targets. Additional studies are needed to assess the long-term effectiveness of RTX in the treatment of patients with SSc.

Keratan sulfate (KS) is a glycosaminoglycan that is enriched in vertebrate cornea, cartilage, and brain. During embryonic development, highly sulfated KS (HSKS) is first detected in the developing notochord and then in otic vesicles; therefore, HSKS has been used as a molecular marker of the notochord. However, its biosynthetic pathways and functional roles in organogenesis are little known. Here, I surveyed developmental expression patterns of genes related to HSKS biosynthesis in Xenopus embryos. Of these genes, the KS chain-synthesizing glycosyltransferase genes, beta-1,3-N-acetylglucosaminyltransferase (b3gnt7) and beta-1,4-galactosyltransferase (b4galt4), are strongly expressed in the notochord and otic vesicles, but also in other tissues. In addition, their notochord expression is gradually restricted to the posterior end at the tailbud stage. In contrast, carbohydrate sulfotransferase (Chst) genes, chst2, chst3, and chst5.1, are expressed in both notochord and otic vesicles, whereas chst1, chst4/5-like, and chst7 are confined to otic vesicles. Because the substrate for Chst1 and Chst3 is galactose, while that for others is N-acetylglucosamine, combinatorial, tissue-specific expression patterns of Chst genes should be responsible for tissue-specific HSKS enrichment in embryos. As expected, loss of function of chst1 led to loss of HSKS in otic vesicles and reduction of their size. Loss of chst3 and chst5.1 resulted in HSKS loss in the notochord. These results reveal that Chst genes are critical for HSKS biosynthesis during organogenesis. Being hygroscopic, HSKS forms “water bags” in embryos to physically maintain organ structures. In terms of evolution, in ascidian embryos, b4galt and chst-like genes are also expressed in the notochord and regulate notochord morphogenesis. Furthermore, I found that a chst-like gene is also strongly expressed in the notochord of amphioxus embryos. These conserved expression patterns of Chst genes in the notochord of chordate embryos suggest that Chst is an ancestral component of the chordate notochord.

Monte Carlo molecular simulation is a powerful computational method for simulating molecular behavior. It generates samples of the possible states of molecular systems. To generate a sample efficiently, it is advantageous to avoid suggesting extremely high-energy states that would never become possible states. In this study, we propose a new sampling method for Monte Carlo molecular simulation, that is, a continuous normalizing molecular flow (CNMF) method, which can create various probabilistic distributions of molecular states from some initial distribution. The CNMF method generates samples by solving a first-order differential equation with two-body intermolecular interaction terms. We also develop specific probabilistic distributions using CNMF called inverse square flow, which yields distributions with zero probability density when molecule pairs are in close proximity, whereas probability densities are compressed uniformly from the initial distribution in all other cases. Using inverse square flow, we demonstrate that Monte Carlo molecular simulation is more efficient than the standard simulation. Although the increased computational costs of the CNMF method are non-negligible, this method is feasible for parallel computation and has the potential for expansion.

Direct oral anticoagulants (DOACs) have been used to prevent cardiogenic embolism in patients with atrial fibrillation (AF). No evidence has been established for the follow-up renal function evaluation intervals. We hypothesized that a proposed follow-up interval of renal function can be estimated by patient's baseline characteristics including creatinine clearance (CCr).We conducted a single-center retrospective study at Kindai University Hospital from May 2011 to December 2017. Patients were screened and they were enrolled if baseline CCr of ≥50 mL/min. To provide a periodical synchronization for measurements of CCr in all patients, these were evaluated at four different time points (approximately at 3, 6, 9, and 12 months). Primary endpoint was defined as a CCr value of50 mL/min during the follow-up period. We analyzed associations between the cumulative risk for renal endpoint and baseline characteristics by the Kaplan-Meier method and the Cox proportional hazards model.Renal endpoint was associated with age (95% CI: 0.07 to 0.21, p0.01), body weight (95% CI: -0.09 to -0.01, p0.01), CCr (95% CI: -0.18 to -0.07, p0.01), and CHA2DS2-VASc score (95% CI: 0.14 to 0.63, p0.01). Combining baseline CCr of60 mL/min and other risk factors, acceptable intervals for 5% risk levels were 78 days (age ≥75 years old), 100 days (CHA2DS2-VASc score of4 points), and 90 days (body weight60kg), respectively. Under conditions of baseline CCr of60 mL/min, age ≥75 years old, CHA2DS2-VASc score of4 points, or body weight60 kg, an increased risk of renal endpoints is 4.85, 3.29, 1.24, 2.44 fold, respectively.We propose a risk-stratified follow-up interval for renal evaluation in patients with AF and DOACs therapy according to a combination of baseline CCr and other risk factors.