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Abstract We evaluated the association between maternal prenatal folic acid supplement use/dietary folate intake and cognitive development in 4-year-old offspring (N = 3445) using data from the Japan Environment and Children’s Study. Cognitive development was evaluated using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis revealed that offspring of mothers who started using folic acid supplements pre-conception had a significantly higher language-social developmental quotient (DQ) (partial regression coefficient 1.981, 95% confidence interval 0.091 to 3.872) than offspring of mothers who did not use such supplements at any time throughout their pregnancy (non-users). Offspring of mothers who started using folic acid supplements within 12 weeks of gestation had a significantly higher cognitive-adaptive (1.489, 0.312 to 2.667) and language-social (1.873, 0.586 to 3.159) DQ than offspring of non-users. Regarding daily dietary folate intake from preconception to early pregnancy, multiple regression analysis revealed that there was no significant association with any DQ area in the 200 to

Objectives: The relationship between weight-related load and bone mineral density (BMD)/bone microstructure under normal load conditions using high-resolution peripheral quantitative computed tomography (HR-pQCT) remains unconfirmed. The study aims to investigate the differences in effect of body mass index (BMI) on BMD/bone microstructure of loaded and unloaded bones, respectively, in Japanese postmenopausal women. Methods: Fifty-seven postmenopausal women underwent HR-pQCT on the tibia and radius. Correlation analysis, principal component (PC) analysis, and hierarchical multiple regression were performed to examine the relationship between BMI and HR-pQCT parameters. Results: Several microstructural parameters of the tibia and radius correlated with BMI through a simple correlation analysis, and these relationships remained unchanged even with an age-adjusted partial correlation analysis. PC analysis was conducted using seven bone microstructure parameters. The first PC (PC1) reflected all parameters of trabecular and cortical bone microstructures, except for cortical porosity, whereas the second PC (PC2) reflected only cortical bone microstructure. Hierarchical multiple regression analysis indicated that BMI was more strongly related to BMD/bone microstructure in the tibia than in the radius. Furthermore, BMI was associated with trabecular/cortical BMD, and PC1 (not PC2) of the tibia and radius. Thus, BMI was strongly related to the trabecular bone microstructure rather than the cortical bone microstructure. Conclusions: Our data confirmed that BMI is associated with volumetric BMD and trabecular bone microstructure parameters in the tibia and radius. However, although BMI may be more related to HR-pQCT parameters in the tibia than in the radius, the magnitude of association is modest.

We have previously reported that an adenosine deaminase (ADA)-deficient patient treated with T cell-directed gene therapy had an increase in serum IgE levels, despite a marked inversion of the CD4/CD8 ratio. In the present report, we have analyzed the phenotypic and functional profiles of the patient's lymphocytes obtained during the clinical trial. In peripheral blood mononuclear cells (PBMC) that were freshly prepared from the patient, both CD4+ and CD8+ T cell subsets were negative for CD40 ligand (CD40L; CD154) and Fas ligand (FasL; CD95L), while CD20+ B cells constitutively expressed CD40 and HLA-DR and were negative for CD80, CD86 and Fas (CD95). The expression of CD23 was detected on the majority of CD20+ B cells and expression was upregulated by interleukin (IL)-4. Furthermore, the patient's PBMC, which already expressed both germline and mature Ce transcripts in vivo, spontaneously secreted IgE and responded to IL-4 with increased IgE production during in vitro culture. When stimulated with anti-CD3ε monoclonal antibody (mAb), CD8+ T cells from gene-transduced T cells displayed high production of interferon (IFN)-γ, low production of IL-4 and IL-13 and comparable levels of CD40L and FasL expression; however, lined CD8+ T cells from circulating T cells expressing the transgene produced IL-4 and IL-13 together with smaller amounts of IFN-γ and preferably expressed CD40L rather than FasL. Two such CD8+ T cells, in conjunction with the presence of IL-4, supported CD40L-mediated B cell proliferation and IgE production after stimulation and fixation. These results indicate that ADA-deficient B cells are functionally mature and that gene-transduced CD8+ T cells and lined CD8+ T cells containing the transgene exhibit T helper 0- and T cytotoxic (c) 2-like phenotypes, respectively. Our data also suggest that immuno-logic reconstitution with genetically modified CD8+ T cells may promote IgE production.

Rear-foot-elevated split squat (RFESS) is often performed as an alternative to conventional double-leg back squat (DLBS). This study aimed to compare 3-dimensional joint kinetics of DLBS and RFESS using the same relative intensity of loads. Eight male college rugby players performed 3 repetitions of DLBS and RFESS at 10-repetition-maximum (RM) loading. Before testing, both exercises were incorporated into the subjects’ training program with a progressive increase in loads for 4 months. A 3-dimensional optical motion capture system and force platform were used for data collection. The 3-dimensional moments at the knee and hip joints in each of the 3 axes were calculated based on the inverse dynamic procedure. p values < 0.05 were considered statistically significant. The hip extension moment was 44% greater in the RFESS than in the DLBS at the bottom position (p < 0.01) and 47% greater for the peak value (p < 0.01) on harmonic averages. The hip abduction and external rotation moments at the bottom position were also greater in the RFESS than in the DLBS. The findings suggest that the magnitude of hip extension moment per leg in DLBS tends to be restricted to less than that expected from the given strength level. In conclusion, the mechanical contribution of hip extensors per leg can be greater in RFESS than in DLBS when using respective 10RM loads, even if the absolute load is smaller and the trunk is more upright in RFESS. [ABSTRACT FROM AUTHOR]

In the Japanese animation industry, TV stations and film companies generally take the lead in setting up joint ventures called production committees to raise funds. Although there are cases where an animation studio takes the lead in starting a project, it is often difficult for the studio to form a production committee depending on the content of the project and the career of the director. In recent years, crowdfunding has attracted attention as a way of raising funds for production from general consumers. While some projects can raise more than their goals through crowdfunding, many others do not. This study, therefore, attempts to identify what anime crowdfunding backers value in pledging their support. A total of 6,596 comments from backers of three Japanese anime projects funded on the U.S. crowdfunding website Kickstarter were analyzed using a text-mining method. The results showed that most crowdfunding backers placed importance on the rewards and that crowdfunding success is likely to be related to past achievements of the work and its creators, as well as the credibility of the studio. Compared to overseas backers, Japanese backers were found to express their support for the creators more than for the rewards.

Abstract Background Letrozole has been reported to be effective in treating anovulation, preventing ovarian hyperstimulation syndrome (OHSS), and retrieving oocytes in breast cancer patients. However, the role and mechanism of letrozole in follicular development remain unclear. Results We treated mouse preantral follicles with various treatments; we found no significant difference in follicle survival rates in the letrozole (LET) group compared with the control group, but the average diameter of follicles in the LET group tended to be larger (CTRL vs. LET 30, p = 0.064; CTRL vs. LET 100, p = 0.025). The estradiol concentrations in culture media of the LET group were significantly lower than those observed in the control group (CTRL vs. LET 30, p = 0.038; CTRL vs. LET 100, p = 0.025). We further found a marked increase in follicle-stimulating hormone receptor (FSHR) gene expression in response to letrozole treatment (CTRL vs. LET 30, p = 0.075; CTRL vs. LET 100, p = 0.034). This result suggested that increased FSHR expression promotes follicle development. Letrozole inhibited aromatase activity, but the effect was limited. Letrozole did not significantly reduce vascular endothelial growth factor (VEGF) gene expression. Conclusions Letrozole may promote follicle development by increasing the expression of FSHR. Letrozole may be useful for fertility preservation of patients with estrogen-dependent cancers such as breast cancer and various other cancers. Whether letrozole has a direct effect in reducing OHSS requires further investigation.

Abstract Exploratory factor analysis (EFA) has been developed as a powerful statistical procedure in psychological research. EFA’s purpose is to identify the nature and number of latent constructs (= factors) underlying a set of observed variables. Since the research goal of EFA is to determine what causes the observed responses, EFA is ideal for hypothesis-based studies, such as identifying the number and nature of latent factors (e.g., cause, risk factors, etc.). However, the application of EFA in the biomedical field has been limited. Guillain–Barré syndrome (GBS) is peripheral neuropathy, in which the presence of antibodies to glycolipids has been associated with clinical signs. Although the precise mechanism for the generation of anti-glycolipid antibodies is unclear, we hypothesized that latent factors, such as distinct autoantigens and microbes, could induce different sets of anti-glycolipid antibodies in subsets of GBS patients. Using 55 glycolipid antibody titers from 100 GBS and 30 control sera obtained by glycoarray, we conducted EFA and extracted four factors related to neuroantigens and one potentially suppressive factor, each of which was composed of the distinct set of anti-glycolipid antibodies. The four groups of anti-glycolipid antibodies categorized by unsupervised EFA were consistent with experimental and clinical findings reported previously. Therefore, we proved that unsupervised EFA could be applied to biomedical data to extract latent factors. Applying EFA for other biomedical big data may elucidate latent factors of other diseases with unknown causes or suppressing/exacerbating factors, including COVID-19.

Azobenzene-containing block copolymers have been previously developed as light-induced reworkable adhesives that can undergo repeatable bonding/debonding on demand, based on photoisomerization of the azobenzene moiety and concomitant softening/hardening of the azo polymer block. For practical use, the applicability of such adhesives to various types of substrates is important and is thus studied as one of their most fundamental properties in this work. Ultraviolet (UV)-transparent acrylic resin as well as non-transparent polycarbonate resin, polyethylene ones, and metallic aluminum substrates are utilized as substrates. UV-transparent acrylic resin is used as one of two substrates to investigate the photoisomerization process. The bonding/debonding process is successful for these substrates, and single lap shear tests show typical adhesion strengths of 1.5-2.0 MPa for the substrates investigated. UV irradiation induced a decrease in the adhesion strength to 0.03 MPa irrespective of the substrate type, indicating that the mechanism of the detachability is flow of the softened adhesive. Facile removal of the residual adhesive on the substrate is successfully demonstrated after detachment without any damage to the substrates by wiping the substrate with laboratory-grade disposable wipes wet with ethanol. [ABSTRACT FROM AUTHOR]

This research focuses on the Japanese gay TV drama series Ossan’s Love (2018) to investigate why the show attracted not only queer audiences, but also heterosexual audiences by analysing its textual periphery through paratexts such as promotional posters, articles and audience reviews. Normally, publicists tend to avoid emphasising a show’s sexual minority themes in the story, considering that such a polemical theme would narrow the target audience. However, publicity for this show clearly indicated a gay theme in its promotional materials, and the show became popular nationwide. From the perspective of social identity theory, it is difficult to explain how such promotional strategies effectively attracted a heterosexual audience. Through paratextual analysis, this research identified the concept of an ‘ideal society’. At first, some people may think the show is a stereotypical comedy that makes fun of gay people, but they eventually recognise that none of the characters laughs at romance between men. It is likely that the show’s such unbiased setting makes both heterosexual and homosexual audiences comfortable, diminishing the line between different sexual orientations.

Nowadays, online user reviews are becoming increasingly important to moviegoers, especially in choosing specific movies they want to see. However, not every user review is considered influential by consumers. To describe the characteristics of useful reviews, this study focuses on online movie reviews posted on Yahoo! Japan Movies—a site that features a usefulness counter with each review. Three principal characteristics of useful reviews are demonstrated: a) a longer text, b) a high level of verbal expressiveness, and c) references to other reviews. From the perspective of the cultural dimensions theory, it is reasonable that longer, informative texts with rich expressions are preferred by consumers from cultures with high uncertainty-avoidance scores, such as Japan. However, Japan’s potential moviegoers are motivated by reviews reviewing other reviews, even if some comments about the movie are very negative. This study suggests that people have different tendencies on the Internet and that Japanese consumers would rather take risks to have their own opinion regarding the reviews they read.

Background: Although previous studies have suggested that lavender oil promote wound healing, no study has examined the molecular mechanisms of its effect. In this study, we investigated the effect of lavender oil on various steps of wound healing and its molecular mechanism, focusing on transforming growth factor-β (TGF-β). Methods: Circular full-thickness skin wounds were produced on rats. Control solution or lavender oil was topically applied to the wounds on alternating days for 14 days. Results: The area of wounds topically treated with lavender oil was significantly decreased as compared to that of wounds of control rats at 4, 6, 8, and 10 days after wounding. Topical application of lavender oil induced expression of type I and III collagen at 4 days after wounding, accompanied by an increased number of fibroblasts, which synthesize collagen. Induced expression of type III collagen by topical application of lavender oil was reduced to control level at 7 days after wounding although increased expression of type I collagen still continued even at 7 days, suggesting rapid collagen replacement from type III to type I in wounds treated with lavender oil. Importantly, expression of TGF-β in wounds treated with lavender oil was significantly increased as compared to control. Moreover, an increased number of myofibroblasts was observed in wounds treated with lavender oil at 4 days after wounding, suggesting promotion of differentiation of fibroblasts through induction of TGF-β, which is needed for wound contraction. Conclusion: This study demonstrated that topical application of lavender oil promoted collagen synthesis and differentiation of fibroblasts, accompanied by up-regulation of TGF-β. These data suggest that lavender oil has the potential to promote wound healing in the early phase by acceleration of formation of granulation tissue, tissue remodeling by collagen replacement and wound contraction through up-regulation of TGF-β. The beneficial effect of lavender oil on wound healing may raise the possibility of new approaches as complementary treatment besides conventional therapy. [ABSTRACT FROM AUTHOR]

Abstract Polycystic ovary syndrome (PCOS) is an endocrine disease that is common in women in their reproductive period. Patients with this disease suffer from anovulation and hyperandrogenism. Ovulation induction with exogenous gonadotropin often causes ovarian hyperstimulation syndrome because many small antral follicles pause in their growth. Treatment with insulin sensitizers is reportedly effective for both anovulation associated with PCOS, and suppression of excessive follicular growth; however, the underlying mechanism of action remains unknown. Although pioglitazone is known as an insulin sensitizer, it also has a potent modulator of cell growth and apoptosis irrespective of insulin resistance. To clarify the effect of pioglitazone on follicular growth, we performed in vitro culture of murine preantral follicles. Secondary follicles (100-160 μm in diameter) isolated from 6-week-old ICR mice were individually cultured for 13 days. Culture conditions were as follows: 1) follicle-stimulating hormone (FSH; 33 mIU/mL; control), 2) FSH plus dihydrotestosterone (DHT; 500 ng/mL), 3) FSH plus pioglitazone (5 ng/mL), and 4) FSH plus DHT/pioglitazone. Survival rate and follicle diameter were evaluated, and concentrations of estradiol (E2) and vascular endothelial growth factor (VEGF) in culture media were measured. mRNA expression of various growth-promoting factors and Vegf within follicles were also assessed. Although no significant differences were observed with regard to survival rate, follicle diameters on day 13 were significantly different. Compared with the control group, the DHT group showed enhanced growth, while groups administered pioglitazone showed stagnation of the accelerated growth induced by DHT. Although DHT treatment enhanced the expression of bone morphogenetic protein 2 (Bmp2) mRNA, pioglitazone exposure suppressed induction of Bmp2 mRNA by DHT. Vegf mRNA and protein expression were also significantly reduced when pioglitazone was added to culture media containing DHT. Administration of pioglitazone negatively affected follicular growth and VEGF levels, which may suppress excessive follicular growth and prevent ovarian hyperstimulation syndrome.

Abstract Hyperandrogenism is one of the cardinal symptoms in polycystic ovary syndrome and plays a key role in the pathogenesis of polycystic ovary syndrome. However, the precise effects and mechanisms of excess androgen during follicular development are still unclear. Here we investigated the effects of androgen on mouse follicle development in vitro. Androgen did not affect the growth of follicles smaller than 160–180 μm in the presence of follicle-stimulating hormone (FSH). However, in the presence of low FSH, androgen supported the growth of follicles larger than 160–180 μm, a size at which growing follicles acquire FSH-dependency. Androgen did not change the mRNA expression of various growth-promoting factors but did increase mRNA expression of the FSH receptor. We suggest that androgen has a positive impact on follicle development by augmentation of the actions of FSH. Therefore, FSH-responsive but FSH-independent follicles grow in the presence of a certain level of FSH or androgen, and androgen compensates for FSH deficiency in FSH-dependent follicles.

Peculiar findings of orofacial actinomycosis mimicking the clinical appearance of a tumor of the upper gingiva are reported. An 83-year-old man with bleeding of the gingiva visited our hospital. The clinical diagnosis was a benign gingival tumor, and the lesion was surgically removed. Histologically, the excised specimens showed an ulcerative granuloma lesion covered by bacterial colonies consisting of club-shaped filaments. DNA samples were extracted from paraffin sections and examined by polymerase chain reaction (PCR) for Actinomyces species. The PCR products examined by direct DNA sequencing demonstrated the presence of Actinomyces israelii. Finally, a pathological diagnosis was made of a pyogenic granuloma associated with actinomycosis. The PCR method aided the early and exact diagnosis of the paraffin-embedded sample of oral mucosal infectious diseases including actinomycosis. Keywords: Actinomyces israelii, actinomycosis, DNA sequence, nested PCR, pyogenic granuloma

Abstract Background Hyperandrogenism and insulin resistance may be related to the etiology of PCOS. Zucker fa/fa rats with polycystic ovary are obese, have insulin resistance without diabetes mellitus or hyperandrogenism and can be utilized as PCOS model rats without effects of hyperandrogenemia. PCOS patients are reported to have elevated levels of serum anti-Mullerian hormone (AMH), which has an inhibitory action on folliculogenesis, and low levels of serum adiponectin, which blocks apoptosis and induces biological effects in some tissues. Pioglitazone, an insulin sensitizer, is administered to PCOS patients with insulin resistance to induce ovulation but the mechanisms by which this occurs have not been elucidated. Methods We purchased 4-week-old female fatty Zucker fa/fa rats as well as lean Zucker +/+ rats for use as control rats with normal insulin sensitivity. The Zucker fa/fa rats were administered pioglitazone (2.5 mg/kg body weight/day) or a vehicle every day for 14 days in separate groups. The Zucker +/+ rats were also administered the vehicle. After 2 weeks of treatment, they were euthanized and we obtained serum samples and both ovaries and determined the body weight, ovarian weight, and serum AMH, adiponectin, testosterone, and androstenedione levels. We also examined ovarian histology to check follicle numbers by using hematoxylin-eosin staining, and the number of atretic follicles using Tdt-mediated dUTP nick end labeling (TUNEL) methods. Results The Zucker fa/fa rats used as PCO model rats and Pioglitazone treated PCO model rats were significantly heavier than the Zucker +/+ control rats (p

Flexible-robust metal-organic frameworks (MOFs), which exhibit unique hybrid nature comprising both flexible and rigid framework characteristics, exhibit high potential for hydrocarbon separations. However, no clear guidelines have been established to regulate their hybrid characteristics owing to limited understanding of their adsorption mechanism. This study investigates the effects of the particle size of a flexible-robust MOF on its adsorption and structural transition behaviors. The robust nature originates from the structural transition of a metastable guest-free structure, while its flexible nature arises from another guest-free structure. The type of guest-free structure is predominantly determined by the particle size; particles below the critical size are trapped in the metastable guest-free structure. Notably, the critical size varies with the type of guest molecule to be removed; consequently, the difference in critical size results in guest-memory characteristics, enabling guest-free structure switching. These results underscore the importance of controlling the particle size to fine-tune hybrid adsorption characteristics of flexible-robust MOFs. [ABSTRACT FROM AUTHOR]

Abstract Background Although mental health disorders of health care workers in the coronavirus disease 2019 (COVID-19) pandemic have been focused, little is known about the psychological impact on nurses and the influence on their behavior and awareness, such as professionalism and views on life and death, in Japan where there are fewer cases of infection and deaths than in other countries. Moreover, the influence of the pandemic on nursing students is still unclear. Methods An online questionnaire survey was conducted among nurses and nursing students. Feelings during the state of emergency (at the peak of the pandemic) in Japan, changes in behavior and awareness after the rise of COVID-19, and the associated factors influencing these changes were analyzed, comparing nurses with nursing students. Results Significantly increased scores of anxiety/fear (p

Male sterility is one of the reproductive isolation systems in plants and quite useful for F1 seed production. We previously identified three independent quantitative trait loci (QTLs) for male sterility of cultivated strawberry, Here, we identified the specific subgenomes in which these QTLs are located by QTL-seq approach. QTLs qMS4.1, qMS4.2, and qMS4.3 were mapped separately in subgenomes Fvb4-4, Fvb4-3, and Fvb4-1, respectively, in 'Camarosa' genome assembly v. 1.0.a1. Candidate regions of qMS4.1 and qMS4.3 were clearly detected around 12-26 Mb in Fvb4-4 and 12-14 Mb in Fvb4-1, respectively; those of qMS4.2 were fragmented in Fvb4-3, which suggests that some scaffolds were incorrectly assembled in Fvb4-3. qMS4.3 was mapped to chr4X1 of 'Reikou' genome assembly r2.3, and qMS4.1 and qMS4.2 were both mapped to chr4Av, which indicates that differentiation of the subgenomes in which both QTLs are located was insufficient in 'Reikou' r2.3. Although 'Camarosa' genome assembly v. 1.0.a1 is an unphased map, which merges homologous chromosomes into one sequence, 'Reikou' genome assembly r2.3 is a phased map, which separates homologous chromosomes. QTL mapping to different reference genomes clearly showed the specific features of each reference genome, and that using different kinds of reference map could accelerate fine mapping and map-based cloning of certain genes of cultivated strawberry. [ABSTRACT FROM AUTHOR]

Fruit shape of cultivated strawberry (Fragaria × ananassa Duch.) is an important breeding target. To detect genomic regions associated with this trait, its quantitative evaluation is needed. Previously we created a multi-parent advanced-generation inter-cross (MAGIC) strawberry population derived from six founder parents. In this study, we used this population to quantify fruit shape. Elliptic Fourier descriptors (EFDs) were generated from 2 969 two-dimensional binarized fruit images, and principal component (PC) scores were calculated on the basis of the EFD coefficients. PC1-PC3 explained 96% of variation in shape and thus adequately quantified it. In genome-wide association study, the PC scores were used as phenotypes. Genome wide association study using mixed linear models revealed 2 quantitative trait loci (QTLs) for fruit shape. Our results provide a novel and effective method to analyze strawberry fruit morphology; the detected QTLs and presented method can support marker-assisted selection in practical breeding programs to improve fruit shape. [ABSTRACT FROM AUTHOR]