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Abstract In Brillouin optical correlation-domain reflectometry (BOCDR), sinusoidal modulation is applied to the output frequency of a light source, with spatial resolution inversely related to the modulation amplitude. We have developed an effective method to estimate the modulation amplitude using the width of the noise spectrum caused by Rayleigh scattering, eliminating the need for an optical spectrum analyzer or modifications to existing equipment. However, the Rayleigh noise spectrum often displays a three-layered structure, complicating the identification of the appropriate spectral components for estimating the modulation amplitude. In this work, we investigate the origins of this three-layered Rayleigh noise spectrum and identify the directivity of an optical circulator as the source of the third noise component. As replacing the circulator with alternative optical components is not easy, it remains an essential part of the system. Our analysis shows that the third noise component exhibits significantly small variation in spectral width with changes in modulation frequency compared to the first and second components. This characteristic allows for the effective separation and identification of the third noise component, thereby enhancing the accuracy and convenience of modulation amplitude estimation in BOCDR.

AbstractThe gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares’ BM and their role in shaping foals’ GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal GM changed during lactation time; hierarchical cluster analysis divided the fetal GM into three groups corresponding to different time points in foal development. The level of most metabolites in milk decreased over time with increasing milk yield, while threonic acid and ascorbic acid increased. Further analyses revealed gut bacteria that correlated with changes in milk metabolites; for instance, there was a positive correlation between Bacteroidaceae in the foal’s gut microbiota and serine/glycine in the mother’s milk. These findings help improve the rearing environment of lactating horses and establish artificial feeding methods for foals.

Objectives: The aim of this study was to identify the microbiota whose decrease in tumor area was associated with the metastatic process of distal colorectal cancer (CRC). Methods: Twenty-eight consecutive patients with distal CRC undergoing surgical resection in our hospital were enrolled. Microbiota in 28 specimens from surgically resected colorectal cancers were analyzed using 16S ribosomal ribonucleic acid gene amplicon sequencing and the relative abundance (RA) of microbiota was evaluated. The densities of tumor-infiltrating lymphocytes (TIL) and tumor associated macrophages (TAM) in the colorectal cancers were immunohistochemically evaluated. Results: Phocaeicola was the most abundant microbiota in normal mucosa. The RA of Phocaeicola in tumor tissues tended to be lower than that in normal mucosa although the difference was not significant (p=0.0732). The RA of Phocaeicola at tumor sites did not correlate either with depth of tumor invasion (pT-stage) or tumor size, however they were significantly reduced in patients with nodal metastases (p

Abstract Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. The psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

Recent studies have highlighted the impact of disrupted maternal gut microbiota on the colonization of offspring gut microbiota, with implications for offspring developmental trajectories. The extent to which offspring inherit the characteristics of altered maternal gut microbiota remains elusive. In this study, we employed a mouse model where maternal gut microbiota disruption was induced using non-absorbable antibiotics. Systematic chronological analyses of dam fecal samples, offspring luminal content, and offspring gut tissue samples revealed a notable congruence between offspring gut microbiota profiles and those of the perturbed maternal gut microbiota, highlighting the profound influence of maternal microbiota on early-life colonization of offspring gut microbiota. Nonetheless, certain dominant bacterial genera in maternal microbiota did not transfer to the offspring, indicating a bacterial taxonomy-dependent mechanism in the inheritance of maternal gut microbiota. Our results embody the vertical transmission dynamics of disrupted maternal gut microbiota in an animal model, where the gut microbiota of an offspring closely mirrors the gut microbiota of its mother.

Abstract Background Patients with iron deficiency anemia are treated with iron preparations, but gastrointestinal symptoms such as nausea and vomiting occur frequently. These symptoms may negatively affect the quality of life and work productivity in patients with iron deficiency anemia. This study assessed the impact of nausea and vomiting on the quality of life and work productivity of patients taking iron preparations for heavy menstrual bleeding or anemia. Methods An online survey was conducted among patients taking iron preparations for heavy menstrual bleeding or anemia. Demographic data and information about medication use and the health condition were collected. The patients were asked to answer the 5-level EQ-5D version, and work productivity and activity impairment questionnaires. The outcomes were reported by patients in the presences of nausea, vomiting, and nausea or vomiting. The association with the 5-level EQ-5D version utility score for the severity and frequency of the symptoms were also assessed. Results A total of 385 patients were enrolled, and 96 were patients with nausea or vomiting, of which 94 were with nausea and 27 were with vomiting. The 5-level EQ-5D version utility scores for the patients with nausea, vomiting, and nausea or vomiting were significantly lower than those of the patients without these symptoms (p

Abstract In Brillouin optical correlation-domain reflectometry (BOCDR), spatial resolution relies on the modulation amplitude of the light. We propose a Rayleigh-based method that utilizes the spectral width of Rayleigh-induced noise to measure this amplitude without altering the setup or requiring an optical spectrum analyzer. With high frequency resolution and ease of implementation, our approach enhances the convenience and accuracy of spatial resolution evaluation in BOCDR.

Although it has been established that patients with chronic kidney disease and iron deficiency, as indicated by a transferrin saturation of < 20%, are at increased risk of all-cause mortality and cardiovascular events, the optimal management of such patients has not yet been determined. In this post hoc subgroup analysis, we aimed to clarify the effect of ferric citrate hydrate on transferrin saturation in patients with chronic kidney disease and low transferrin saturation (< 20%) undergoing hemodialysis. To accomplish this, we extracted the relevant data on a subset of patients drawn from two previous studies: the ASTRIO study (A Study examining the contribution to Renal anemia treatment with ferric citrate hydrate, Iron-based Oral phosphate binder, UMIN000019176) and a post-marketing surveillance study. The subset of patients used for the present study were those with baseline transferrin saturation < 20%. We found that administration of ferric citrate hydrate increased transferrin saturation and maintained transferrin saturation at approximately 30%. However, because we did not have access to data on all-cause mortality or cardiovascular events, we could not ascertain whether the frequency of these outcomes was reduced in parallel with improvements in transferrin saturation. Further large studies are required.

Early life environment influences mammalian brain development, a growing area of research within the Developmental Origins of Health and Disease framework, necessitating a deeper understanding of early life factors on children’s brain development. This study introduces a mouse model, LAO1 knockout mice, to investigate the relationship between breast milk, the gut microbiome, and brain development. The results reveal that breast milk‘s reactive oxygen species (ROS) are vital in shaping the neonatal gut microbiota. Decreased hydrogen peroxide (H2O2) levels in milk disrupt the gut microbiome and lead to abnormal metabolite production, including D-glucaric acid. This metabolite inhibits hippocampal myelin formation during infancy, potentially contributing to behavioral abnormalities observed in adulthood. These findings suggest that H2O2 in breast milk is crucial for normal gut microbiota formation and brain development, with implications for understanding and potentially treating neurodevelopmental disorders in humans.

Abstract An optically active π-stacked molecule was synthesized incorporating planar chiral [2.2]paracyclophane and o-carborane units to impart circularly polarized luminescence and aggregation-induced emission properties to the molecule. The molecule exhibited a strong emission from the aggregated state in a mixed solvent system (H2O/THF) and the solid state in the PMMA matrix. In the aggregated state, weak circularly polarized luminescence was observed owing to the random intermolecular orientation. On the other hand, the circularly polarized luminescence was clearly observed in the PMMA film containing 1 wt% molecule. Theoretical studies using time-dependent density functional theory reproduced the molecule’s circular dichroism and circularly polarized luminescence properties.

Purpose: Iliofemoral ligament (ILFL) is a capsular ligament located in the anterosuperior part of the hip joint capsule and contributes to hip joint stability. The purpose of this study was to compare the surgical outcomes of resection versus preservation procedure of the medial arm of the ILFL in total hip arthroplasty (THA) using the anterolateral approach. Methods: Perioperative outcomes, complication, implant placement and patient-reported outcome measures (PROMs) were evaluated in 42 patients in the resection group and 38 patients in the preservation group. As a PROM, the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ), was administered at 6 months, 1 year and 2 years postoperatively. Results: There was no significant difference in perioperative outcomes, complication and implant placement between the two groups. Satisfaction for the hip joint condition (80.6 ​± ​22.4 vs 89.2 ​± ​20.1), JHEQ pain score (21.5 ​± ​4.5 vs 24.1 ​± ​5.2) at 6 months, and JHEQ pain score (21.6 ​± ​5.1 vs 23.5 ​± ​5.5) at 1 year were significantly better in the preservation group than in the resection group. At 2 years postoperatively, no significant difference was found in PROMs between the two groups. Conclusion: Our results indicate that preservation of the medial arm of the ILFL in THA improves pain during the first postoperative year without increased complications or disadvantages of implant placement. Preserving the medial arm of the ILFL may be a safe and effective option to improve the early clinical outcomes after THA using the anterolateral approach.

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria.

Activation-induced markers (AIMs) are frequently analyzed to identify re-activated human memory T cells. However, in pigs the analysis of AIMs is still not very common. Based on available antibodies, we designed a multi-color flow cytometry panel comprising pig-specific or cross-reactive antibodies against CD25, CD69, CD40L (CD154), and ICOS (CD278) combined with lineage/surface markers against CD3, CD4, and CD8α. In addition, we included an antibody against tumor necrosis factor alpha (TNF-α), to study the correlation of AIM expression with the production of this abundant T cell cytokine. The panel was tested on peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin, Staphylococcus enterotoxin B (SEB) or PBMCs from African swine fever virus (ASFV) convalescent pigs, restimulated with homologous virus. PMA/ionomycin resulted in a massive increase of CD25/CD69 co-expressing T cells of which only a subset produced TNF-α, whereas CD40L expression was largely associated with TNF-α production. SEB stimulation triggered substantially less AIM expression than PMA/ionomycin but also here CD25/CD69 expressing T cells were identified which did not produce TNF-α. In addition, CD40L-single positive and CD25+CD69+CD40L+TNF-α− T cells were identified. In ASFV restimulated T cells TNF-α production was associated with a substantial proportion of AIM expressing T cells but also here ASFV-reactive CD25+CD69+TNF-α− T cells were identified. Within CD8α+ CD4 T cells, several CD25/CD40L/CD69/ICOS defined phenotypes expanded significantly after ASFV restimulation. Hence, the combination of AIMs tested will allow the identification of primed T cells beyond the commonly used cytokine panels, improving capabilities to identify the full breadth of antigen-specific T cells in pigs.

Abstract Spatial colocation has been studied in many contexts including locations of urban facilities, industry entities and businesses. However, identifying colocations among a small number of facilities and establishments holds the risk of introducing false positive in that such a spatial arrangement may have occurred by chance. To account for the association between a group of facilities that frequently colocate with each other, this study proposes a two-step approach consisting of identifying statistically significant clusters of each facility type using the False Discovery Rate (FDR) controlling procedure, and subsequently measuring the colocation of those clusters with the frequent-pattern-growth (FP-growth) algorithm. Empirical analysis of 6 million business and industrial establishments across Japan suggests that 10 out of 86 industry types form clear colocations and their colocations form a multi-layered, cascading structure. The number of layers in the multi-layered structure reflect the city size and the strength of the association between the colocated clusters of industries. These patterns illustrate the utility of detecting colocation of clusters towards understanding the agglomeration of different businesses. The proposed method can be applied to other contexts that would benefit from investigations into how different types of spatial features can be linked with each other and how they form colocations.

Abstract Background The purpose of this study was to establish an estimating equation to predict the 5-level EQ-5D version (EQ-5D-5L) utility score in patients taking iron preparations for heavy menstrual bleeding (HMB) or anemia and to evaluate whether the presence of nausea or vomiting was a significant predictor of EQ-5D-5L-based quality of life. Methods A cross-sectional survey was conducted to collect EQ-5D-5L utility scores and other patient reported outcomes from 385 patients taking iron preparations for HMB or anemia who were selected from the disease patient panel. Using the utility scores as objective variables, explanatory variable candidates were selected considering correlations, multicollinearity, and clinical validity. Predicting models were constructed using regression-based models (linear model, generalized linear model (GLM), Tobit model). Stepwise regression method was applied for selecting statistically significant (p

To enable the long-term use of existing wooden structures, appropriately evaluating the extent of damage of the biodeterioration of structural performance, including members and joint systems, is necessary. To give one example, accurately estimating the single shear strength performance of nail and screw joints with decay is crucial. Therefore, this study proposes a method to model this by dividing wood into multiple layers with different strength performance, considering the grade of deterioration in a cross-section of decayed wood. The model was used to differentiate the sound layer and three decayed layers (multilayer) according to the extent of the damage. The estimated values, which were produced using the proposed model, were compared to the single shear strength of screw and nail joints with decay using two species of wood, namely Abies sachalinensis (Todomatsu) and Cryptomeria japonica (Sugi). The results point to a good fit between the average value of the experimental results and the estimated values of the proposed model. Compared with the existing (single-layer) model, the proposed model improved the accuracy of estimating the strength of wood undergoing early deterioration and therefore was considered usable.

Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age.

Abstract Background Resistance training adaptively increases muscle strength and mass, contributing to athletic performance and health promotion. Dietary intervention with natural foods provides nutrients that help accelerate muscle adaptation to training. Matcha green tea contains several bioactive factors such as antioxidants, amino acids, and dietary fibers; however, its effect on muscle adaptation is unclear. In this study, we aimed to investigate the effects of matcha beverage intake on muscle adaptation to resistance training. Methods Healthy, untrained men were randomized into placebo and matcha groups. Participants consumed either a matcha beverage containing 1.5 g of matcha green tea powder or a placebo beverage twice a day and engaged in resistance training programs for 8 (trial 1) or 12 weeks (trial 2). Results In trial 1, maximum leg strength after training tended to increase more in the matcha group than that in the placebo group. In the matcha group, subjective fatigue after exercise at 1 week of training was lower than that in the placebo group. Gut microbe analysis showed that the abundance of five genera changed after matcha intake. The change in Ruminococcus, Butyricimonas, and Oscillospira compositions positively correlated with the change in maximum strength. In trial 2, the change in skeletal muscle mass in response to training was larger in the matcha group. In addition, the salivary cortisol level was lower in the matcha group than that in the placebo group. Conclusion Daily intake of matcha green tea beverages may help in muscle adaptation to training, with modulations in stress and fatigue responses and microbiota composition.

ABSTRACTFecal microbiota is a significant factor determining the cause, course, and prognosis of Crohn’s disease (CD). However, the factors affecting mucosa-associated microbiota (MAM) remain unclear. This retrospective study examined the differences in ileal MAM between CD patients and healthy controls and investigated the factors affecting MAM in CD patients to clarify potential therapeutic targets. Ileal MAM was obtained using brush forceps during endoscopic examination from 23 healthy controls and 32 CD patients (most were in remission). The samples’ microbiota was profiled using the Illumina MiSeq platform. Compared to controls, CD patients had significantly reduced α-diversity in the ileum and a difference in β-diversity. The abundance of butyric acid-producing bacteria in the ileal MAM was significantly lower in CD patients with a history of abdominal surgery than in those without. Because butyric acid is a major energy source in the intestinal epithelium, its metabolism via β-oxidation increases oxygen consumption in epithelial cells, reducing oxygen concentration in the intestinal lumen and increasing the abundance of obligate anaerobic bacteria. The suppression of obligate anaerobes in CD patients caused an overgrowth of facultative anaerobes. Summarily, reducing the abundance of butyric acid-producing bacteria in the ileal MAM may play an important role in CD pathophysiology.

Abstract Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.

Introduction: Prevention of tooth loss contributes to an extended life expectancy, namely longevity. Aging-related oral hypofunction, including tooth loss, markedly increases the risks of functional disorder and mortality. Dysbiosis of the oral microbiome has recently been associated with various diseases, such as liver cirrhosis, pancreatic cancer, colorectal cancer, and inflammatory bowel disease. Therefore, the relationship between the oral microbiome and systemic health has been attracting increasing attention. In the present study, we examined oral function and the oral microbiome in the elderly in a world-leading longevity area. Materials and Methods: An oral examination, chewing ability/tongue-lip motor function/saliva tests, and a metagenomic analysis with a 16S rRNA gene-targeting next-generation sequencer were conducted on 78 subjects aged ≥80 years. Twenty-six healthy individuals aged between 20 and 39 years were also investigated as controls. The data obtained were statistically analyzed. The protocol of the present study was approved by the Ethics Review Board of our university (ERB-C-885). Results: Chewing ability, tongue–lip motor function, and saliva volume were normal in elderly subjects with a current tooth number ≥20, but were significantly lower in those with a current tooth number

Abstract Background For the optimal management of patients with both allograft kidneys and native kidney diseases, the recognition of the histological features associated with older age is important. This is because most pathological findings are non-specific. Central fibrous areas (CFAs) have recently been proposed to be age-related. However, the components of CFAs and whether CFAs are observed in various kidney diseases remain undetermined. This cross-sectional study was undertaken to clarify the histological features, epidemiology, and clinicopathological features of CFAs. Methods One hundred and one consecutive kidney needle biopsy specimens were retrospectively collected from seven facilities in the Hokuriku region and diagnosed at the Kanazawa University Hospital in 2015. First, the components of CFAs were analyzed using normal histostaining, immunostaining, and electron microscopy. Second, the patients were divided into two groups (CFA [+] or CFA [−]) according to the presence of CFA in the obtained samples. Clinical and histological features were compared between the two groups, and factors associated with CFA formation were determined using univariate and multivariate analyses. The number of CFAs per specimen was counted in the CFA (+) group. Third, the presence of myofibroblasts in CFA was examined by immunostaining. Results CFAs were observed in 56 of 101 patients (55.4%) with various kidney diseases. CFAs consist of fibrillar collagens (collagen I and III) in addition to non-fibrillar collagens (collagen IV and VI), as confirmed by electron microscopy. Clinically, the CFA (+) group was older and had a significantly higher prevalence of hypertension and hyperlipidemia than the CFA (−) group. Histologically, elastofibrosis of the interlobular artery, arteriolar hyalinosis, and membranous nephropathy were significantly more evident in the CFA (+) group than in the CFA (−) group. Multivariate analysis revealed that older age was the sole factor associated with CFA formation. Finally, 27 of 58 (46.6%) CFA-containing glomeruli in 26 cases included alpha-smooth muscle actin-positive cells in or adjacent to the CFA. Conclusions CFAs consist of fibrous collagens in addition to matrix collagens. CFA formation is associated with older age and was observed in various kidney diseases.

Summary: Habitual exercise alters the intestinal microbiota composition, which may mediate its systemic benefits. We examined whether transplanting fecal microbiota from trained mice improved skeletal muscle metabolism in high-fat diet (HFD)-fed mice. Fecal samples from sedentary and exercise-trained mice were gavage-fed to germ-free mice. After receiving fecal samples from trained donor mice for 1 week, recipient mice had elevated levels of AMP-activated protein kinase (AMPK) and insulin growth factor-1 in skeletal muscle. In plasma, bile acid (BA) deconjugation was found to be promoted in recipients transplanted with feces from trained donor mice; free-form BAs also induced more AMPK signaling and glucose uptake than tauro-conjugated BAs. The transplantation of exercise-acclimated fecal microbiota improved glucose tolerance after 8 weeks of HFD administration. Intestinal microbiota may mediate exercise-induced metabolic improvements in mice by modifying circulating BAs. Our findings provide insights into the prevention and treatment of metabolic diseases.

Abstract Background As carcinogenic risk factors, environmental factors can be classified into physical, biological, and chemical factors. Subperiosteal implants (SIs) are associated with complications, such as framework exposure, infection, and fistula formation. A current hypothesis suggests that chronic mechanical irritation could be a co-factor in carcinogenesis, while peri-implantitis might be an initiating or promoting agent in the development of oral mucosal cancer. Herein, we report a case of squamous cell carcinoma (SCC) around a maxillary SI associated with chronic mechanical irritation and peri-implantitis as physical and biological factors, respectively. Case presentation A 74-year-old male patient presented with severe mobility of the SI and an undermined ulcer with induration, accompanied by a palatal fistula and the exposure of the metal framework. The SI had been placed on the maxilla for the occlusal reconstruction of the molar area 20 years ago. An incisional biopsy of the ulcer revealed SCC (cT4aN2cM0). Neoadjuvant chemotherapy was initiated, followed by bilateral neck dissection and partial resection of the maxilla with SI removal. Energy-dispersive X-ray analysis suggested that the SI was fabricated using pure titanium, and titanium was absent in the specimen. Scanning electron microscopy of the SI in contact with the SCC showed a few microcracks, suggesting pitting corrosion. Discussion Chronic mechanical irritation due to the mobility of an improperly designed SI can be a physical factor, and prolonged peri-implantitis without regular maintenance can be a biological factor in carcinogenesis. Improperly designed main struts and a large masticatory force in the molar area resulted in deterioration of the retention and mobility of the SI. The screw and framework frequently moved on mastication and came in direct contact with the ulcer as chronic mechanical irritation. Bacterial invasion into the subperiosteal space expanded by the mobility of the metal framework led to peri-implantitis. The influence of chemical factors was considered relatively small in this case since the patient had no history of smoking or drinking, and titanium was absent in the specimen. Therefore, it is conceivable that SCC can arise owing to persistent inflammation caused by chronic mechanical irritation and peri-implantitis as physical and biological factors, respectively.

Polycrystalline ice is known to exhibit macroscopic anisotropy in relative permittivity (ɛ) depending on the crystal orientation fabric (COF). Using a new system designed to measure the tensorial components of ɛ, we investigated the dielectric anisotropy (Δɛ) of a deep ice core sample obtained from Dome Fuji, East Antarctica. This technique permits the continuous nondestructive assessment of the COF in thick ice sections. Measurements of vertical prism sections along the core showed that the Δɛ values in the vertical direction increased with increasing depth, supporting previous findings of c-axis clustering around the vertical direction. Analyses of horizontal disk sections demonstrated that the magnitude of Δɛ in the horizontal plane was 10–15% of that in the vertical plane. In addition, the directions of the principal axes of tensorial ɛ in the horizontal plane corresponded to the long or short axis of the elliptically elongated single-pole maximum COF. The data confirmed that Δɛ in the vertical and horizontal planes adequately indicated the preferred orientations of the c-axes, and that Δɛ can be considered to represent a direct substitute for the normalized COF eigenvalues. This new method could be extremely useful as a means of investigating continuous and depth-dependent variations in COF.

Introduction Mucin‐producing adenocarcinoma of the prostate is a rare disease that includes prostate adenocarcinoma with mucus production, secondary adenocarcinoma from the bladder or colorectum, and adenocarcinoma from the urothelium of the prostatic urethra. We describe prostate‐specific antigen‐negative mucin‐producing urothelial‐type adenocarcinoma of the prostate. Case presentation The patient had urinary retention and a serum prostate‐specific antigen level of 0.74 ng/mL. Computed tomography and magnetic resonance imaging revealed a prostate tumor with a mucous component. We diagnosed adenocarcinoma by prostate biopsy and subsequently performed robot‐assisted radical prostatectomy. Mucin‐producing urothelial‐type adenocarcinoma of the prostate was diagnosed by pathological examinations. Lung metastasis, developing within 3 months after surgery, was treated using chemotherapy. Conclusion Endocrine therapy is ineffective for mucin‐producing urothelial‐type adenocarcinoma of the prostate. Mucin‐producing urothelial‐type adenocarcinoma of the prostate diagnosis requires pathological and immunohistochemical analyses. It is important to surgically remove the primary lesion, and robot‐assisted radical prostatectomy may provide an effective approach. Multimodal therapy is essential to treat for mucin‐producing urothelial‐type adenocarcinoma of the prostate.

The initial colonization and early development of the intestinal microbiome are important stages in the growth of calves during pre-weaning. This study investigated temporal changes in the diversity and composition of the fecal microbiota, focusing on the first 2 weeks after birth, with the aim of identifying intestinal bacteria and blood metabolites that are associated with calf diarrhea. In this study, 10 calves were fed colostrum on day 0 after birth, whole milk from days 2 to 5, and milk replacer from day 6. Six calves showed mild diarrhea in the second week (i.e., from day 8 to 14). We observed dramatic changes in the development of the fecal microbiome from day 2 to 14 and found several bacterial species, such as Lactobacillus and Collinsella, changing significantly in abundance during the milk transition (i.e., from day 4 to 10). In investigating whether there is an association between the microbiome and the milk transition, we found the level of hypotaurine and D-xylose to be significantly higher in whole milk from days 4 and 5 than in milk replacer. A comparison of four healthy calves and six diarrheal calves revealed that the diarrheal calves had a low abundance of Collinsella on day 10. Furthermore, we explored plasma metabolites statistically correlated with the change of fecal Collinsella and found a high level of dimethylglycine in healthy calves. Taken together, these findings suggest a possible link between temporary changes in the fecal microbiome and neonatal diarrhea during the milk transition in calves.

Abstract Micro‐speckle patterns were fabricated using α‐Al2O3 and SiC micro‐particles for in‐plane strain distribution measurement at temperatures up to 1500°C using an ultraviolet high‐temperature observation system (UV‐HTOS) combined with a digital image correlation (DIC) technique. The experimental results showed that the measured mean surface strains of α‐Al2O3 were in good agreement with the calculated values obtained from thermal expansion coefficient and temperature difference. The proposed speckle pattern could be used for strain distribution measurement without degradation even after heating up to 1500°C. The results also demonstrated that the pattern fabricated in this study is effective to understand the heterogeneous deformation mechanism in composite materials applied in high‐temperature structural components.

Abstract This study aimed to clarify the factors underlying the discrepancy that has been noted between estimated glomerular filtration ratio (eGFR) measured using serum creatinine (Cr) and eGFR using serum cystatin C (CysC) in patients with rheumatoid arthritis (RA) and to identify those patients whose renal function should be evaluated using CysC. We retrospectively evaluated clinical features, disease activity, Steinbrocker radiological staging, and co-morbidities (diabetes mellitus, hypertension, dyslipidemia) in 238 RA patients. eGFR using serum creatinine (eGFR-Cr) and eGFR using serum cystatin C (eGFR-CysC) were calculated using the new Japanese coefficient-modified Modification of Diet in Renal Disease study equation. To clarify the cause(s) of differences of 20% or more between the two eGFRs, we divided our RA patients into Group A (eGFR-Cr/eGFR-CysC ≥ 1.2) and Group B (eGFR-Cr/eGFR-CysC

Abstract Background The objectives of this study were to assess radiolucent lines around a highly porous titanium cup (Tritanium) using digital tomosynthesis and to investigate the clinical and radiographic factors associated with radiolucent lines on tomosynthesis. Methods Fifty-five patients underwent total hip arthroplasty using a Tritanium cup, and digital tomosynthesis and plain radiography were performed at 1 week, 6 months, 1 year, and 2 years after surgery. The radiolucent lines around the cup were measured on both DTS and plain radiography at each postoperative period. Clinical evaluations were performed by the Japanese Orthopaedic Association hip disease evaluation questionnaire (JHEQ), and revision surgeries were examined. Based on the presence of radiolucent lines on digital tomosynthesis at 2 years postoperatively, patients were divided into RL (+) and RL (−) groups and investigated for related factors. Results There were 20 cases in the RL (+) group and 35 cases in the RL (−) group, and no revision surgeries were required. Statistically, there were more cases with radiolucent lines on digital tomosynthesis (45.4% at 1 week and 36.3% at 2 years) than on plain radiography (9.1% at 1 week and 9.1% at 2 years) at each postoperative point. Logistic analysis showed no significant associations between the presence of radiolucent lines at 2 years on digital tomosynthesis, and the JHEQ parameters of pain (p = 0.937), movement (p = 0.266), or mental status (p = 0.404). Conclusion In a short-term evaluation up to 2 years, digital tomosynthesis detected more radiolucent lines around the titanium cups than plain radiography. The occurrence of radiolucent lines was not related to the postoperative clinical evaluation.

In order to confirm the effect of multiple moderate earthquakes on the response deformation of wooden houses at the time of a major earthquake, an earthquake response analysis, considering performance deterioration due to repeated small deformations, was conducted. As a result, it was found that the effect of multiple moderate earthquakes on the mean response deformation during a major earthquake was small. On the other hand, in some cases, the response deformation was up to 1.2 times larger than that of the sound case. In the case of a house where the response deformation was near the criteria of continuous use and/or collapse, the influence of the response magnification was large. This shows the importance of giving higher seismic performance compared to the standard. The response deformation during repeated medium earthquakes may increase for houses with considerably low seismic performance. However, for the houses that meet current standards, little to no increase in response deformation was seen.

Carbon-fiber-reinforced epoxy-matrix composite (CFRP) laminates with thin plies have strong damage-resistance properties compared with standard prepregs. The static and fatigue tensile fracture behavior of cross-ply CFRP laminates with thin plies should be further studied to establish the applicability of thin-ply prepregs for industrial structures. In this study, the static and fatigue tensile properties of cross-ply, high-strength polyacrylonitrile (PAN)-based carbon-fiber (T800SC)-reinforced epoxy-matrix composites with thin plies were investigated. The fiber orientations of the CFRP specimens were set to cross-ply with [0/90]10S (subscript S means symmetry), [(0)5/(90)5]2S, and [(0)10/(90)10]S. The static and fatigue tensile characteristics of the cross-ply CFRPs with thick plies with [0/90]2S and [(0)2/(90)2]S were also investigated for comparison. Under static loading, the tensile strength and failure strain of the thinnest 90°-ply-CFRP specimens were more than 5% higher than those of the other 90°-ply-thickness specimens. However, the tensile moduli and Poisson’s ratios were comparable between the cross-ply CFRPs with thin and thick plies. Under fatigue loading, the fatigue responses of the thinnest 90°-ply-CFRP specimens were 3% higher than those of the other 90°-ply-thickness specimens during lower-fatigue-cycle testing (5 cycles). However, during higher-fatigue-cycle testing (>105 cycles), the fatigue responses decreased, with a decrease in the 90°-ply thickness, and the fatigue characteristics of the thinnest 90°-ply-CFRP specimen were 7% lower than those of the other cross-ply thin- and thick-ply-CFRP specimens.

Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.

Abstract The factors predicting hand osteoarthritis (HOA) in patients remain unknown. We aimed to investigate the usefulness of serum hyaluronic acid (sHA) levels in predicting HOA progression from a 6-year longitudinal epidemiological study. A total of 417 participants in the Iwaki cohort were followed-up over 6 years. Hand and knee radiographs taken at baseline and follow-up were scored according to Kellgren–Lawrence grades and Kallman score. Participants were classified into the HOA group and the non-HOA group. sHA levels at baseline were determined by ELISA. Correlations between sHA levels, the number of involved joints, and Kallman score were estimated. Factors related to the incidence or progression of HOA over 6 years were analyzed. The prevalence of HOA was 19.9% at baseline, and 3.6 ± 2.1 joints were involved. sHA levels in the HOA group at baseline were significantly higher than in the non-HOA group (p

Short-term traffic state prediction has been an integral part of intelligent transportation systems. Currently, many prediction methods that model traffic dynamics have been proposed. However, only a few of them utilize the relationship among traffic variables represented on the fundamental diagram of traffic flows for prediction. This study proposes traffic speed prediction models based on a threshold error correction model. The proposed model expresses long-run fundamental relationships between speed and density, which differ in non-congested and congested states separated by a speed or density threshold, and the short-run fluctuation of traffic variables that are cointegrated. Using traffic sensor data for more than 300 days on 96 links of arterial roads in Naha City, Japan, the feasibility of the proposed method is evaluated through the analysis of estimated parameters and prediction accuracy. The results confirmed that the proposed method estimates the fundamental speed–density relationship in non-congested and congested states and improves the prediction accuracy using simple threshold error correction models, feed-forward neural networks. The proposed method supports vector regression for most of the links.

To establish a mouse model of weak depression, we raised 6-week-old C57BL/6N mice in single (SH) or group housing (GH) conditions for 2 weeks. The SH group showed less social interaction with stranger mice, learning disability in behavioral tests, and lower plasma corticosterone levels. The cecal microbiota of the SH group showed significant segregation from the GH group in the principal coordinate analysis (PCoA). Transcriptome analysis of the amygdala and liver detected multiple differentially expressed genes (DEGs). In the amygdala of SH mice, suppression of the cyclic adenine monophosphate (cAMP) signal was predicted and confirmed by the reduced immunoreactivity of phosphorylated cAMP-responsive element-binding protein. In the liver of SH mice, downregulation of beta-oxidation was predicted. Interestingly, the expression levels of over 100 DEGs showed a significant correlation with the occupancy of two bacterial genera, Lactobacillus (Lactobacillaceae) and Anaerostipes (Lachnospiraceae). These bacteria-correlated DEGs included JunB, the downstream component of cAMP signaling in the amygdala, and carnitine palmitoyltransferase 1A (Cpt1a), a key enzyme of beta-oxidation in the liver. This trans-omical analysis also suggested that nicotinamide adenine dinucleotide (NAD) synthesis in the liver may be linked to the occupancy of Lactobacillus through the regulation of nicotinamide phosphoribosyltransferase (NAMPT) and kynureninase (KYNU) genes. Our results suggested that SH condition along with the presence of correlated bacteria species causes weak depression phenotype in young mice and provides a suitable model to study food ingredient that is able to cure weak depression.

Abstract Aims/Introduction Gut dysbiosis is generally associated with type 2 diabetes mellitus. However, the effect of habitual dietary intake on gut dysbiosis in Japanese patients with type 2 diabetes mellitus has not yet been explicated. This study investigated whether alteration of the gut microbiota was influenced by dietary intake of sucrose in Japanese patients with type 2 diabetes mellitus. Materials and Methods In this cross‐sectional study, 97 patients with type 2 diabetes mellitus and 97 healthy individuals were matched by age and sex, and then, fecal samples were obtained. Next‐generation sequencing of the 16S ribosomal ribonucleic acid gene was carried out, and functional profiles for the gut microbiota were analyzed. We selected the top 30 gut microbial genera and top 20 functional profiles for the gut microbiota specified by the weighted average difference method. The association between gut microbial genera or functional profiles and habitual dietary intake was investigated by Spearman’s rank correlation coefficient, and then, clustering analysis was carried out to clarify the impact of habitual dietary intake. Results The Actinobacteria phylum was highly abundant in patients with type 2 diabetes mellitus, whereas the Bacteroidetes phylum was less abundant. Diabetic‐type gut microbes, specifically Bacteroides and Bifidobacterium, were altered by sucrose intake at the genus level. Furthermore, sucrose intake was associated with glycolysis/gluconeogenesis in the diabetic‐type functional profiles of the gut microbiota. Conclusions The gut microbiota and functional profiles for the gut microbiota in patients with type 2 diabetes mellitus were significantly different from those in healthy individuals. Furthermore, we showed that sucrose intake was closely associated with these differences.

Laboratory animals are used for scientific research in various fields. In recent years, there has been a concern that the gut microbiota may differ among laboratory animals, which may yield different results in different laboratories where in-vivo experiments are performed. Our knowledge of the gut microbiota of laboratory-reared common marmosets (Callithrix jacchus) is limited; thus, in this study, we analyzed the daily changes in fecal microbiome composition, individual variations, and effects of the birth facility in healthy female laboratory-reared marmosets, supplied by three vendors. We showed that the marmoset fecal microbiome varied among animals from the same vendor and among animals from different vendors (birth facility), with daily changes of approximately 37%. The fecal microbiome per vendor is characterized by alpha diversity and specific bacteria, with Bifidobacterium for vendor A, Phascolarctobacterium for vendor B, and Megamonas for vendor C. Furthermore, we found that plasma progesterone concentrations and estrous cycles were not correlated with daily fecal microbiome changes. In contrast, animals with an anovulatory cycle lacked Megamonas and Desulfovibrio bacteria compared to normal estrous females. This study suggests that the source of the animal, such as breeding and housing facilities, is important for in-vivo experiments on the marmoset gut microbiota.

The relationship between morphology (grain-size order) and mechanical properties of Al _x CoCrCuFeNi (x = 0.3 and 1) was evaluated. Both alloys were prepared using the arc-melting method. Crystal structures with x = 0.3, face-centered cubic (FCC), and body-centered cubic (BCC) structures were observed for x = 1, the typical crystal structures of Al _x CoCrCuFeNi. The alloys prepared via arc melting exhibited two different microstructures: a Cu-rich region (area I) and an equiatomic region (area II). Microstructures of the as-fabricated specimen were homogenized through heat treatment at 600 and 1000 °C for 5 h. Although the homogenization of the microstructure proceeded, areas I and II remained after the heat treatment. In particular, the area I composition was inconsistent with the predicted phase diagram. Tensile tests for these alloys revealed that the tensile strength of x = 1 (∼310–1100 MPa) is higher than that of x = 0.3 (∼320–660 MPa), whereas the fracture strain of x = 1 (∼0.03–0.09) is lower than that of x = 0.3 (∼0.06–0.26). These results indicate that the increase in Al content caused an increase in strength and brittle fracture because it also caused an increase in the formation of the BCC and B2 phases, which required higher stresses for the movement of dislocations than the FCC phase. Because the tensile properties of Al _x CoCrCuFeNi are comparable to those of conventional alloys, such as Ti alloys and steels, a design with a moderate composition for stronger and tougher Al _x CoCrCuFeNi is required to apply high entropy alloys to structural materials.

Smoking affects eating habits; however, few studies on smoking and the gut microbiota have reported the effects of diet in detail. This cross-sectional study aimed to determine the association between smoking and the gut microbiota, considering the impact of smoking on dietary intake. Dietary habits and the composition of the gut microbiota were assessed in 195 men with type 2 diabetes (164 non-current smokers and 31 current smokers) using a brief self-administered diet history questionnaire and 16S ribosomal RNA gene sequencing of fecal samples. The data were compared according to the current smoking status of the participants. Current smokers had high alcohol and sugar/sweetener intake and low fruit intake. The proportion of the Coprococcus genus was higher among current smokers. Multiple regression analysis adjusted for current smoking, age, exercise habits, alcohol intake, sugar and sweetener intake, and fruit intake showed that smoking was associated with the proportion of the Coprococcus genus. Current smoking was associated with both dietary intake and composition of the gut microbiota. Although dietary intake should be considered when investigating the association between smoking and the gut microbiota, the results suggest that the direct effect of smoking is more significant.

To quantify the flood risk awareness of real estate market participants and residents, previous studies analyzed the effect of flood risks on residential property values. However, most studies focused on the impact of recent flood events and the publication of new flood risk information; the behavior in flood-prone regions in which repeated damages occurred and lessons learned consequently has not been the focus of analysis. Moreover, there is a growing national concern in Japan about an increase in future flood risks due to climate change, although their effect on property values has not been discussed. In this study, we analyzed residential property values in Nagoya City (Aichi Prefecture, Japan), a megacity that has experienced significant flood damage in major historical and recent floods. The main objective of this study is to determine the effects of past and recent flood experiences and the increasing concerns about flood risks on recent residential property values. The results revealed that historical flood damage had the largest impact on residential property values in Nagoya City, and devaluation increased due to growing concerns about natural disasters in Japan. The disclosure of flood risk information also had an impact on property values, increasing devaluation after disclosure. On the contrary, the occurrence of recent floods did not have an impact on property values, suggesting that flood risk awareness had already been strong in the target area. These findings are different from those of many previous studies. The observed trends in residential property values in the target area are likely a characteristic response in flood-prone regions, where flood risk awareness is enhanced due to repeated flood damage.

Abstract The pulse thermography (PT) technique was applied to the detection of the delamination of a multi-layered coating system composed of mullite/Si onto a reaction-bonded SiC substrate. The potential evaluation was carried out in order to detect internal delamination in multi-layered material system. Moreover, the observation of the cross sections and 3D views obtained by X-ray computed tomography (CT) indicated that the delamination occurred at the interface between the top coat and the bond coat layers. The changes in the temperature distribution obtained by PT indicated the existence of a delamination area in the top coat layer of the mullite. In particular, the lower temperature region corresponded to the delamination area. The experimental results confirmed that the PT technique is effective with respect to the internal delamination of multi-layered coating system.

Growing evidence indicates that porcine colostral exosomes may contribute to the healthy development of piglets. Here, we evaluated in vitro the effect of porcine milk-derived exosomes, in particular colostral exosomes, on T cells in the peripheral blood of suckling piglets. A total of seven sows and thirteen suckling piglets were used. Peripheral blood mononuclear cells (PBMCs) from suckling piglets were cultured with or without milk-derived exosomes (control). Using flow cytometry, the proportion of each T cell subset in cultured PBMCs was analyzed three days post-incubation. PBMCs cultured with porcine colostral exosomes had a higher proportion of CD3+CD4−CD8+ T cells (cytotoxic T cells; Tc) than the control. However, exosomes induced no increase in the Tc cell population in PBMC whose endocytosis was inhibited. We further measured the concentrations of cytokines in the culture supernatant. Exosome-treated PBMCs had a higher cytokine IL-2 concentration than the control. The present study demonstrated that porcine colostral exosomes could increase the Tc cell proportion in the peripheral blood of suckling piglets, with the underlying mechanism believed to be the stimulation of IL-2 production in PBMCs via endocytosis. Moreover, our results suggested that porcine colostral exosomes were involved in the development of cellular immunity in suckling piglets.

The purpose of this study is to utilize timber material to enhance the in-plane shear strength and deformation capacity of a brick wall. The proposed strengthening method is light-weight and easy to assemble and includes a timber frame, plywood panel, M12 threaded rod with chemical epoxy, and the hold-down anchor. To evaluate the effectiveness of the reinforced brick wall, three walls were tested under a cyclic horizontal load and static compression stress: the brick wall (BW wall), the reinforced brick wall with timber (BW-T wall), and the reinforced brick wall with timber and the hold-down anchor (BW-TA wall). The proposed prediction method of the Kamiya and Inayama Murakami models assessed the BW-TA wall. The rocking was caused by the failure of BW and BW-T walls. However, because the BW-T wall failed in the lowest part of the wall, the timber part retained the original shape of the brick wall. When the diagonal on the BW-TA wall failed, the horizontal load at maximum load increased by 22%, and the drift angle calculated from the diagonal measurement increased 4.6 times.

Geospatial phenomena often have spatial heterogeneity, which is caused by differences in the data generation process from place to place. There are two types of spatial heterogeneity: continuous and discrete, and there has been much discussion about how to analyze one type of spatial heterogeneity. Although geospatial phenomena can have both types of spatial heterogeneities, previous studies have not sufficiently discussed how to consider these two different types of spatial heterogeneity simultaneously and how to detect them separately, which may lead to biased estimates and the wrong interpretation of geospatial phenomena. This study proposes a new approach for the analysis of spatial data with both heterogeneities by combining the eigenvector spatial filtering-based spatially varying coefficient (ESF-SVC) model, which assumes the continuous spatial heterogeneity and generalized lasso (GL) estimation, which assumes discrete spatial heterogeneity and proposes the ESF-GL-SVC model. The performance of ESF-GL-SVC was evaluated through experiments based on a Monte Carlo simulation and confirms that the ESF-GL-SVC showed better performance in estimating coefficients with both types of spatial heterogeneity than the previous two models. The application of the apartment rent data showed that the ESF-GL-SVC outputs the result with the smallest BIC value, and the estimated coefficients depict continuous and discrete spatial heterogeneity in the dataset. Reasonable coefficients were estimated using the ESF-GL-SVC, although some coefficients by ESF-SVC were not.

Susceptibility to pathogen infections and efficacy of vaccination highly depend on the immune status of the piglet. Here, we measured immunocytes in piglets from birth to weaning to elucidate how immunocyte populations change during development and are affected by weaning. Crossbred piglets were used. Suckling piglets were euthanized at 1, 7, 14, 21, 28 or 35 days old (3~4 piglets at each time point). In addition, seven piglets were weaned at 21 days old, with four being euthanized at 28 days old and the remaining at 35 days old. Piglet carcasses were dissected, and blood, mesenteric lymph nodes (MLN) and spleen were sampled. In total, seven antibodies were used to stain the immunocyte population. Dynamics of myeloid (CD3–SWC3+CD16+), natural killer (NK; CD3–SWC3–CD16+), killer T (CD3+CD8+), helper T (CD3+CD4+) and B (CD3–CD21+) cells were analyzed. Percentage of innate immunity cells such as myeloid cells declined (p < 0.05) from the first day after birth. In contrast, percentage of NK cells increased in piglets while they were still suckling. Killer T, helper T, and B cell populations increased around 2~3 weeks after birth. No significant differences in the populations of the evaluated cell types were observed between suckling and weaned piglets at least for 14 days post weaning.

The microbiota associated with relapse in patients with quiescent ulcerative colitis (qUC) remains unclear. Our objective was to analyze the fecal microbiota of Japanese patients with qUC and identify the relapse-associated microbiota. In this study, 59 patients with qUC and 59 healthy controls (HCs) were enrolled (UMIN 000019486), and their fecal microbiota was compared using 16S rRNA gene amplicon sequencing. We followed their clinical course up to 3.5 years and analyzed the relapse-associated microbiota. Potential functional changes in the fecal microbiota were evaluated using PICRUSt software and the Kyoto Encyclopedia of Genes and Genomes database. There were significant differences in fecal microbiota diversity between HC and qUC subjects, with 13 taxa characterizing each subject. Despite no significant difference in variation of microbiota in a single sample (α diversity) between patients in sustained remission and relapsed patients, the variation in microbial communities between samples (β diversity) was significantly different. Prevotella was more abundant in the sustained remission patients, whereas Faecalibacterium and Bifidobacterium were more abundant in the relapsed patients. We clustered the entire cohort into four clusters, and Kaplan–Meier analysis revealed the subsequent clinical course of each cluster was different. We identified 48 metabolic pathways associated with each cluster using linear discriminant analysis effect size. We confirmed the difference in microbiota between patients with qUC and HCs and identified three genera associated with relapse. We found that the clusters based on these genera had different subsequent clinical courses and activated different metabolic pathways.