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Abstract Background The placenta is essential for nutrient exchange and hormone production between the mother and the developing fetus and serves as an invaluable model for epigenetic research. Most epigenetic studies of the human placenta have used whole placentas from term pregnancies and have identified the presence of partially methylated domains (PMDs). However, the origin of these domains, which are typically absent in most somatic cells, remains unclear in the placental context. Results Using whole-genome bisulfite sequencing and analysis of histone H3 modifications, we generated epigenetic profiles of human cytotrophoblasts during the first trimester and at term, as well as human trophoblast stem cells. Our study focused specifically on PMDs. We found that genomic regions likely to form PMDs are resistant to global DNA demethylation during trophectoderm reprogramming, and that PMDs arise through a slow methylation process within condensed chromatin near the nuclear lamina. In addition, we found significant differences in histone H3 modifications between PMDs in cytotrophoblasts and trophoblast stem cells. Conclusions Our findings suggest that spatiotemporal genomic features shape megabase-scale DNA methylation patterns, including PMDs, in the human placenta and highlight distinct differences in PMDs between human cytotrophoblasts and trophoblast stem cells. These findings advance our understanding of placental biology and provide a basis for further research into human development and related diseases.

Abstract The level of dynamic mechanical instability between the bony parts of the ankle joint provides important information on biomechanical function. However, the dynamics of the distance between the talus and lateral malleolus during gait remain unclear. This study aimed to compare the distance between the talus and lateral malleolus and the ankle joint angles during the stance phase of gait between individuals with chronic ankle instability (CAI) and healthy adults. The comparison was conducted using a synchronized ultrasound (US) imaging with a three-dimensional motion analysis (MA) system. This cross-sectional study included 12 participants (5 males, 7 females; age, 20.5 ± 1.8 years; height, 166.6 ± 9.4 cm; body weight, 60.2 ± 5.3 kg; body mass index, 21.7 ± 2.0 kg/m2; 16 feet) with CAI and 10 healthy controls (4 males, 6 females; age, 21.2 ± 1.6 years; height, 164.6 ± 10.5 cm; body weight, 56.8 ± 11.3 kg; body mass index, 20.8 ± 2.6 kg/m2; 20 feet). The distance between the talus and lateral malleolus during gait was significantly increased in the CAI group compared with that in the control group throughout the stance phase. The ankle dorsiflexion angle was smaller in the CAI group during the middle and terminal stance phases. Additionally, the ankle inversion angle was greater in the CAI group than in the control group. Our findings show the application of the synchronized US and MA system in the assessment of mechanical instability in CAI group, which may be used to determine treatment efficacy.

Abstract Background Oral bacteria are altered in patients with diabetes, cardiovascular diseases, and cancer. However, the oral microbiome of patients with chronic kidney disease (CKD), including those receiving renal replacement therapy, remains unclear. Here, we report changes in the oral microbiome of patients with CKD. Methods In total, 103 individuals were recruited for this study, including 46 with stages 3–5 and 22 with stage 5D CKD, including those receiving renal replacement therapy (CKD group), and 35 with CKD stages 1–2. The oral microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol. Results At the genus level, the periodontal pathogens Tannerella, Fusobacterium, and Capnocytophaga were more abundant in the CKD group (stages 3–5) than in the control group (linear discriminant analysis score > 3). Streptococcus, which has been shown to be involved in dental plaque formation, and Capnocytophaga were abundant in the CKD group (stage 5D). The unweighted UniFrac distance revealed a separation trend among CKD stages 1–2, 3–5, and 5D groups (stages 1–2 versus 3–5: P = 0.137. ; stages 3–5 versus 5D: P = 0.002). As the CKD stage progressed, the number of bacteria with significant differences qualitative and quantitative changes were observed in the β-diversity assessment. Conclusions Our findings highlight that periodontal disease bacteria increased in the CKD (stages 3–5 and 5D) group, including those receiving renal replacement therapy.

Selecting the most appropriate mining method to recover mineral resources is a critical decision-making task in mining project development. This study introduces an artificial intelligence-based mining methods recommendation system (AI-MMRS) for the pre-selection of underground mining methods. The study integrates and evaluates the capability of two approaches for mining methods selection (MMS): the memory-based collaborative filtering (CF) approach aided by the UBC-MMS system to predict the top-3 relevant mining methods and supervised machine learning (ML) classification algorithms to enhance the effectiveness and novelty of the AI-MMRS, addressing the limitations of the CF approach. The results reveal that the memory-based CF approach achieves an accuracy ranging from 81.8% to 87.9%. Among the classification algorithms, artificial neural network (ANN) and k-nearest neighbors (KNN) classifiers perform the best, with accuracy levels of 66.7% and 63.6%, respectively. These findings demonstrate the effectiveness and viability of both approaches in MMS, acknowledging their limitations and the need for continuous training and optimization. The proposed AI-MMRS for the pre-selection stage supplemented by the direct involvement of mining professionals in later stages of MMS, has the potential to significantly aid in the MMS decision-making, providing data-driven and experience-based recommendations following the ongoing evolution of mining practices.

Study Design A retrospective cohort study. Purpose To investigate the sagittal plane configuration of the entire spine and its association with the risk of adjacent segment degeneration (ASD) after posterior lumbar interbody fusion (PLIF). Overview of Literature Although PLIF has demonstrated satisfactory clinical outcomes, it is associated with ASD. However, the geometric mechanical changes that contribute to the occurrence of ASD are not well characterized. Methods Radiological parameters were extracted from the whole lateral radiographs. Patients were divided into two groups: the ASD group (segmental kyphosis of ≥10º, and/or a ≥50% loss of disc height, and/or ≥3 mm of anteroposterior translation) and the non-ASD group. Results All 112 included patients underwent PLIF for lumbar degenerative diseases. The minimum follow-up period was 2 years, with an average follow-up time of 63.6 months. Fifty-two patients (46.4%) were classified into the ASD group and of these, 13 required reoperation due to failure of conservative treatment. Patients with ASD exhibited significantly more caudal and posterior inflection vertebrae (IV), while the lumbar apical vertebra was significantly more caudal immediately after surgery. The IV position was identified as a significant risk factor for ASD, and the ASD incidence was significantly higher in the group where IV ≤5 (L1 vertebral body) than in the group where IV ≥5.5 (T12–L1 disc) (69.0% vs. 38.6%). Conclusions The IV position is a significant risk factor for ASD development. Although it is difficult to control intraoperative IV levels, we note a high risk of ASD in patients with IV lower than T12–L1.

Background: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to

Abstract This study aimed to translate a web-based hamstring outcome score (HaOS) questionnaire to the Japanese context. First, the validity and reliability of the translated questionnaires were examined among Japanese athletes. Second, the association between the previous history of hamstring strain and HaOS was examined. The translation was performed according to internationally recognized methodologies. A total of 233 athletes were asked to complete the HaOS questionnaire, and four questions were added to examine the content validity of the questionnaire. Intraclass correlation coefficient (ICC) was calculated to evaluate the test–retest reliability. Internal consistency was determined by calculating Cronbach’s alpha values. The translated questionnaires had high acceptance and compliance rates, with a response rate of 84.4%. The ICC for each scale ranged from 0.80 to 0.93, and Cronbach's α from 0.72 to 0.96, confirming good reliability and high internal consistency. HaOS of the previous injury group (93.4 [78.9, 100]) was significantly lower than that of the healthy group (86.2 [68.1, 100]) (p

Abstract Background Tibetan highlanders have adapted to hypoxic environments through genetic mechanisms that avoid hemoglobin concentration increases and prevent polycythemia. Recently, sex differences in hemoglobin dynamics with age have been reported among Tibetan highlanders living in Tsarang. Additionally, concerns have been raised that dietary changes associated with modernization may increase the risk of polycythemia and lifestyle-related diseases among Tibetan highlanders. However, the relationship between genetic polymorphisms and the risk of lifestyle-related diseases in Tibetan highlanders has been investigated in only a few regions. This study aims to elucidate whether polymorphisms in genes related to hypoxic adaptation are associated with the incidence of lifestyle-related diseases and polycythemia and whether these polymorphisms affect hemoglobin dynamics in the residents of Tsarang, Mustang, Nepal. Methods Health checkup data from individuals living in Tsarang in Mustang District, Nepal, collected in 2017, were used to determine the prevalence of obesity, hypertension, diabetes, hypoxemia, and polycythemia. DNA was extracted from whole-blood samples, and data for the single-nucleotide polymorphisms (SNPs) rs13419896 (EPAS1), rs12619696 (EPAS1), and rs2790859 (EGLN1) were obtained using real-time PCR. The health checkup data were statistically analyzed to determine the associations of these diseases with polymorphisms in genes related to hypoxic adaptation. Results A total of 168 participants, comprising 78 males and 90 females, were included in the final analysis. In terms of the prevalence of each disease, only the prevalence of polycythemia significantly differed between sexes (p

Abstract Background Chemotherapy including cisplatin is recommended for the treatment of advanced bladder cancer, but its effectiveness is limited due to the acquisition of drug resistance. Although several mechanisms of cisplatin resistance have been reported, there are still many unknowns, and treatment of cisplatin-resistant bladder cancer remains difficult. Accordingly, in this study, we aimed to identify and characterize microRNAs involved in cisplatin resistance. Methods Small RNA sequencing analysis was performed to search for microRNAs related to cisplatin resistance. The identified microRNAs were then characterized using gain-of-function studies, sensitivity analysis, target gene analysis, and cellular assays. Results We identified miR-424-5p as a candidate microRNA that was downregulated in cisplatin-resistant strains compared with parental strains. Notably, in gain-of-function studies, miR-424-5p suppressed the proliferative ability of cisplatin-resistant bladder cancer (CDDP-R BC). Furthermore, miR-424-5p restored sensitivity to cisplatin. RNA sequence analysis revealed seven candidate genes targeted by this microRNA. Among them, cyclin E1 (CCNE1) was chosen for subsequent analyses because its expression was upregulated in cisplatin-resistant cells compared with parental cells and because recent studies have shown that CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. Therefore, we performed functional analysis using the PKMYT1 inhibitor RP-6306 and demonstrated that RP-6306 inhibited cell growth through suppression of mitotic entry and restored cisplatin sensitivity in CDDP-R BC. Conclusions Overall, our findings provided insights into the development of novel therapeutic strategies for CDDP-R BC.

Objectives This study aimed to investigate the association and population-attributable fraction (PAF) of maternal smoking and secondhand smoke (SHS) exposure during pregnancy with placental abruption.Design Prospective cohort study.Setting 15 regional centres in Japan.Participants Pregnant women registered between January 2011 and March 2014 from the Japan Environment and Children’s Study.Outcome measures Data were transcribed from medical records and two self-administered questionnaires. The outcome measure was the incidence of placental abruption. Maternal smoking exposure during pregnancy was categorised based on the number of cigarettes smoked (≤10 or ≥11 cigarettes per day). SHS exposure during pregnancy was evaluated by frequency and duration (almost never or never, 1–3 days/week and/or

Through an enzymatic process, arrowroot (Maranta arundinacea) porous starch produces pores on the surface of starch granules, making it a potential bioadsorbent and encapsulation material. Snakehead fish albumin (Channa striata) is a sensitive component whose functional properties must be preserved. Therefore, encapsulating albumin through spray drying is necessary to protect it from external environmental factors. This study aimed to evaluate the encapsulation efficiency as well as morphological, physical, and chemical properties of encapsulated albumin using arrowroot porous starch. The P-50, porous starch:gum arabic (50:50) formula demonstrated the highest encapsulation efficiency of 98.88 %. Scanning electron microscopy revealed that porous starch adsorbs albumin on its surface. X-ray diffraction and Fourier-transform infrared profiles indicated an amorphous structure with minimal crystallinity, confirming the adsorption of albumin onto porous starch. The water content and water activity values of powder encapsulated with porous starch were better than those of native starch. Therefore, porous starch from arrowroot can be effectively used as an albumin encapsulant.

BackgroundGrowing evidence supports the importance of characterizing the organizational patterns of various cellular constituents in the tumor microenvironment in precision oncology. Most existing data on immune cell infiltrates in tumors, which are based on immune cell counts or nearest neighbor-type analyses, have failed to fully capture the cellular organization and heterogeneity.MethodsWe introduce a computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), that jointly measures immune cell partitioning between tumor epithelial and stromal areas and immune cell clustering versus dispersion. As proof-of-principle, we applied TIPC to a prospective cohort incident tumor biobank containing 931 colorectal carcinoma cases. TIPC identified tumor subtypes with unique spatial patterns between tumor cells and T lymphocytes linked to certain molecular pathologic and prognostic features. T lymphocyte identification and phenotyping were achieved using multiplexed (multispectral) immunofluorescence. In a separate hepatocellular carcinoma cohort, we replaced the stromal component with specific immune cell types-CXCR3+CD68+ or CD8+-to profile their spatial relationships with CXCL9+CD68+ cells.ResultsSix unsupervised TIPC subtypes based on T lymphocyte distribution patterns were identified, comprising two cold and four hot subtypes. Three of the four hot subtypes were associated with significantly longer colorectal cancer (CRC)-specific survival compared to a reference cold subtype. Our analysis showed that variations in T-cell densities among the TIPC subtypes did not strictly correlate with prognostic benefits, underscoring the prognostic significance of immune cell spatial patterns. Additionally, TIPC revealed two spatially distinct and cell density-specific subtypes among microsatellite instability-high colorectal cancers, indicating its potential to upgrade tumor subtyping. TIPC was also applied to additional immune cell types, eosinophils and neutrophils, identified using morphology and supervised machine learning; here two tumor subtypes with similarly low densities, namely 'cold, tumor-rich' and 'cold, stroma-rich', exhibited differential prognostic associations. Lastly, we validated our methods and results using The Cancer Genome Atlas colon and rectal adenocarcinoma data (n = 570). Moreover, applying TIPC to hepatocellular carcinoma cases (n = 27) highlighted critical cell interactions like CXCL9-CXCR3 and CXCL9-CD8.ConclusionsUnsupervised discoveries of microgeometric tissue organizational patterns and novel tumor subtypes using the TIPC algorithm can deepen our understanding of the tumor immune microenvironment and likely inform precision cancer immunotherapy.

Background: Relationships between cancer onset, progression, and inflammation have been reported; yet, the significance of inflammatory markers before and after treatment with nanoliposomal irinotecan and fluorouracil with folic acid (NFF) is unclear. Objectives: We aimed to (1) investigate whether worsening inflammation is associated with disease progression and whether it can be used as a biomarker by comparing inflammatory markers before and after treatment with NFF and (2) verify which is a superior biomarker. Design: This was a preplanned analysis of a retrospective cohort of the NAPOLEON-2 study, a multicenter observational study. Patients from 20 institutions were enrolled. Those with unresectable pancreatic cancer who received NFF as a second-line or later-line treatment between June 1, 2020, and May 31, 2021, were included. Methods: The primary endpoint was overall survival, and the main secondary endpoint was progression-free survival. The following inflammatory markers were assessed: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutrition Index (PNI), C-reactive protein/albumin ratio (CAR), Glasgow prognostic score (GPS), Prognostic Index (PI), and Komori score. Results: A total of 161 patients were enrolled. The CAR, NLR, GPS (1 vs 2), PI (1 vs 2), PNI, and Komori score were useful pre-NFF biomarkers (hazard ratios (HRs): 2.59, 2.28, 2.76/3.35, 2.16/18.89, 2.13, and 3.39, respectively). The CAR, NLR, GPS (compared with a score of 1/2), and PI (compared with a score of 1/2) were useful post-NFF biomarkers (HRs: 2.63, 1.88, 2.54/3.09, 2.30/5.39, respectively). In terms of the receiver operating characteristic curve and Akaike information criterion, the CAR, GPS, and PI showed favorable trends, and overall, CAR was a useful biomarker. Conclusion: Inflammatory markers can be used as biomarkers both before and after NFF treatment, and CAR may be useful. We hope these findings will contribute to the selection of appropriate treatment options.

Objectives Japanese people are known to get the least amount of sleep in the world, and in particular, the increase in sleep deprived young women is a serious problem. Sleep deprivation is considered to be associated with depression, but the factors involved in this problem are unclear. This study aimed to examine the association between sociodemographic factors, lifestyle choices, sleep-related characteristics and depressive symptoms in young Japanese women.Design Web-based cross-sectional study.Participants We distributed an online survey aiming to recruit young Japanese women ages 18 to 29 from 8 November 2022 to 2 February 2023.Primary and secondary outcome measures Sociodemographic, lifestyle, health, and sleep characteristics were compared among participants according to the presence or absence of depressive symptoms, as assessed by the Patient Health Questionnaire 2 (Cut-off value: 3 points).Results Overall, 540 participants aged between 19 and 29 years were enrolled in the study. The overall prevalence of depressive symptoms was 15.6%. The group with depressive symptoms had a higher rate of current smoking status at 38.5% (unadjusted OR 3.716, 95% CI 1.624 to 8.502). Multiple logistic analyses revealed that depressive symptoms were associated with increased sleep onset latency (β=0.282; p=0.048; OR, 1.325; 95% CI, 1.003 to 1.752) and daytime dysfunction (β=0.550; p

Objectives To investigate the relationship between sleep quality and perimenstrual symptoms among Japanese female students.Design Observational, cross-sectional, online surveySetting We used an online questionnaire to collate responses from Japanese female students on sleep quality and perimenstrual symptoms.Participants A total of 298 female students aged 18–25 years in Japan were included in this study.Primary and secondary outcome measures The Menstrual Distress Questionnaire (MDQ) was used to assess the severity of perimenstrual symptoms for three periods—premenstrual, menstrual and postmenstrual—and the Japanese version of the Pittsburgh Sleep Quality Index was used to assess sleep quality. The MDQ scores were compared between two groups (normal-sleep quality and low-sleep quality) using Mann-Whitney U test. In addition, multiple logistic regression analysis was performed, and the MDQ subscales that showed significant differences between the groups were used as independent variables. The MDQ subscale that was strongly associated with sleep quality was calculated.Results Of the female students, 160 were classified into the normal-sleep quality group and 138 into the low-sleep quality group. The total MDQ scores were significantly higher in the low-sleep quality group at all phases of the menstrual cycle (respectively p

Acid mine drainage (AMD) is generally managed via active or passive treatment strategies. Between the two, passive treatment is explored as a more sustainable alternative, especially for abandoned and legacy mines due to their low energy, manpower and material requirements. Recent studies of the authors have explored the use of limestone and waste materials like low-grade ores (LGO), fly ash (FA), and concrete wastes (CW) for AMD treatment and found that although these materials generated alkalinity individually, they could only partially remove sulfate (SO42−) and some heavy metals. To address this limitation, a mixed media approach using these four materials is proposed to neutralize the pH of AMD and maximize metal and SO42− removal. A total of twenty (20) mixtures of the four materials were identified based on the response surface methodology (RSM) experimental design. Laboratory-scale experiments using simulated AMD were performed to assess the performance of each mixture by monitoring the pH, oxidation-reduction potential (Eh), electrical conductivity (EC), and concentrations of metals and SO42−. Based on the results, three optimized mixed media compositions were identified. Overall, simulated AMD passively treated by the optimized mixed media compositions met the Philippine effluent standards except for SO42−.

Aim: This study was performed to evaluate the association between left atrial (LA) stiffness and outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and Results: This study involved 279 patients with aortic stenosis (AS) who underwent TAVI at Kumamoto University Hospital between 2015 and 2023. During a median follow-up of 468 days (interquartile range: 258–825 days), 42 deaths occurred. Pre-TAVI echocardiography showed that the LA stiffness index (E/e′ ratio/LA strain during the reservoir phase [LASr]) was significantly higher in the all-cause death group than in the survival group (2.80 ± 2.56 vs. 1.70 ± 1.23, p

The joint Simon effect refers to inhibitory responses to spatially competing stimuli during a complementary task. This effect has been considered to be influenced by the social factors of a partner: sharing stimulus-action representation. According to this account, virtual interactions through their avatars would produce the joint Simon effect even when the partner did not physically exist in the same space because the avatars are intentional agents. To investigate this, we conducted two joint experiments in which participants controlled avatars as their agents in immersive virtual environments. In Experiment 1, participants were asked to touch a virtual button through their avatars when a target color of an object was presented. The target position was manipulated to be compatible with the button (compatible stimulus) or incompatible with the button (incompatible stimulus). In Experiment 2, the task was identical to that in Experiment 1 except that participants' gaze position was either visualized or not during the task. We hypothesized that visualizing the partner's gaze would enhance the joint Simon effect because gaze is a cue to mentalize others' internal states. The results showed that avatar-based interactions more significantly delayed responses for the incompatible than for the compatible stimulus. However, inconsistent with our hypothesis, visualizing the partner's gaze position did not influence responses for spatially competing stimuli. These results suggest that virtual interactions through avatar agents can produce the joint Simon effect even when the partner does not physically exist in the same space.

Prolonged exposure to teratogens is known to cause neural tube defects (NTDs), a severe malformation of the central nervous system (CNS) that significantly contributes to global infant mortality. In recent years, exposure to nanoplastics (NPs) has been linked to faulty neural crest closure and altered neurulation by altering cellular adhesion molecules and accumulation of plastic particles in the neural tube leading to NTDs. However, research on the influence of various types of microplastics (MPs) on malformations of the CNS are still limited. In this study, we investigated whether MPs of polytetrafluoroethylene (PTFE)—a type of plastic commonly used as non-stick coatings of cooking utensils can affect angiogenesis and CNS development using ducks as model organisms. PTFE MPs were administered on Day 3 of duck embryo development at varying concentrations (0.01 mg/ml, 0.1 mg/ml, 1 mg/ml, and 5 mg/ml), and angiogenesis was evaluated using a chorioallantoic membrane (CAM) assay. Gross morphology and histology of the spinal column and brain were analyzed on Days 8 and 18, respectively. FTIR confirmed PTFE's structure, while SEM and DLS analyses showed particle sizes between 300 nm and 5 μm, classifying them as MPs. High concentrations (5 mg/ml) of PTFE MPs treated on duck embryos resulted in a 35 % mortality rate and reduced vascular density, suggesting anti-angiogenic effects. Brain and spinal abnormalities, such as encephalomalacia and spinal cord discontinuities were observed in the PTFE-treated embryos. Based on these results, PTFE is an anti-angiogenic and teratogenic agent affecting the development of duck embryos.