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Background: It is well known that maternal diet affects the development of offspring. Herein, the relationship between maternal intake of fermented foods during pregnancy and offspring development was investigated. Methods: The diet of 103,060 pregnant women at >4 months of gestation who were enrolled in the Japan Environment and Children's Study was analyzed. Their intake levels of fermented soybeans (miso and natto), yogurt, and cheese were investigated. The developmental status of the offspring at 3 years of age was assessed using the Ages and Stages Questionnaires (ASQ-3). Multivariable logistic regression analysis was performed to determine the risk of maternal intake levels of the fermented foods associated with subsequent developmental delay in the offspring. Results: Intake of cheese was associated with a reduced risk of child developmental delay in all intake level groups from the second quartile onward. Intakes of miso and yogurt were associated with a reduced risk of developmental delay in communication skills in the fourth quartile. There was no association between intake of natto and developmental delay. Conclusion: Maternal consumption of fermented foods during pregnancy may reduce the risk of later developmental delay in offspring. It is therefore important to review the mother's diet for fermented foods during pregnancy. However, further studies are warranted to evaluate the factors influencing the association between diet and offspring development. [ABSTRACT FROM AUTHOR]

Talking to oneself using the second-person pronoun ["you" has been shown to enhance performance and autonomous motivation in English speakers. However, there is a lack of evidence on whether it can be replicated for speakers of other languages, such as Japanese, in which the grammatical subject is usually omitted in daily conversation. Based on self-determination theory, the present study examined the effects of second-person self-talk for a sample of Japanese individuals on task performance, intrinsic motivation, and three styles of extrinsically motivated regulations: identified, introjected, and external. We randomly assigned 411 undergraduate students to either an experimental group (second-person self-talk, first-person self-talk, and non-subject self-talk) or a control group. An anagram task was used to assess performance. No significant difference was found between the four groups in intrinsic motivation or performance. For extrinsic regulations, the results showed that first-person self-talk led to higher external regulation than non-subject self-talk and the control group. The possible reason for contradictory findings with our hypothesis and implications have been discussed. [ABSTRACT FROM AUTHOR]

Dach1 is highly expressed in normal podocytes, but this expression rapidly disappears after podocyte injury. To investigate the role of Dach1 in podocytes in vivo, we analyzed global, podocyte-specific, and inducible Dach1 knockout mice. Global Dach1 knockout (Dach1-/-) mice were assessed immediately after birth because they die within a day. The kidneys of Dach1-/- mice were slightly smaller than those of control mice but maintained a normal structure and normal podocyte phenotypes, including ultrastructure. To study the role of Dach1 in mature podocytes, we generated Dach1 knockout mice by mating Dach1fl/fl mice with Nphs1-Cre or ROSA-CreERT2 mice. Due to inefficient Cre recombination, only a small number of podocytes lacked Dach1 staining in these mice. However, all eleven Nphs1-Cre/Dach1fl/fl mice displayed abnormal albuminuria, and seven (63%) of them developed focal segmental glomerulosclerosis. Among 13 ROSA-CreERT2/Dach1fl/fl mice, eight (61%) exhibited abnormal albuminuria after treatment with tamoxifen, and five (38%) developed early sclerotic lesions. These results indicate that while Dach1 does not determine the fate of differentiation into podocytes, it is indispensable for maintaining the normal integrity of mature podocytes. [ABSTRACT FROM AUTHOR]

Trapeziometacarpal osteoarthritis (TMC-OA) reduces the range of motion (ROM) of the thumb. However, the kinematic change achieved through surgical treatment remains unclear. Therefore, to quantify the kinematic change following TMC-OA surgery, we performed a three-dimensional motion analysis of the thumb using an optical motion capture system preoperatively and 1 year postoperatively in 23 patients with TMC-OA scheduled for arthrodesis (AD) or trapeziectomy with suspensionplasty (TS). Eighteen hands of nine healthy volunteers were also included as controls. Both procedures improved postoperative pain and Disability of the Arm, Shoulder and Hand scores, and AD increased pinch strength. The ROM of the base of the thumb was preserved in AD, which was thought to be due to the appearance of compensatory movements of adjacent joints even if the ROM of the TMC joint was lost. TS did not improve ROM. Quantifying thumb kinematic changes following TMC-OA surgery can improve our understanding of TMC-OA treatment and help select surgical procedures and postoperative assessment. [ABSTRACT FROM AUTHOR]

Proteins overexpressed in early-stage cancers may serve as early diagnosis and prognosis markers as well as targets for cancer therapies. In this study, we examined the expression of an essential amino acid carrier SLC7A5 (LAT1, CD98, or 4F2 light chain) in cancer tissue from two well-annotated cohorts of 575 cases of early-stage and 106 cases of late-stage colorectal cancer patients. Immunohistochemistry showed SLC7A5 overexpression in 72.0% of early-stage and 56.6% of late-stage cases. SLC7A5 expression was not influenced by patient gender, age, location, or mismatch repair status, although it appeared to be slightly less prevalent in tumors of mucinous differentiation or with lymphovascular invasion. Statistical analyses revealed a positive correlation between SLC7A5 overexpression and both overall survival and disease-free survival in early-stage but not late-stage cancers. Co-expression analyses of the TCGA and CPTAC colorectal cancer cohorts identified a network of gene transcripts positively related to SLC7A5, with its heterodimer partner SLC3A2 having the highest co-expression score. Network analysis uncovered the SLC7A network to be significantly associated with ncRNA such as tRNA processing and the mitotic cell cycle. Since SLC7A5 is also a marker of activated lymphocytes such as NK, T, and B lymphocytes, SLC7A5 overexpression in early colorectal cancers might trigger a strong anti-tumor immune response which could results in better clinical outcome. Overall, our study provides clear evidence of differential SLC7A5 expression and its prognostic value for early-stage colorectal cancer, although the understanding of its functions in colorectal tumorigenesis and cancer immunity is currently rather limited and awaits further characterization. [ABSTRACT FROM AUTHOR]

Transcriptional response to changes in oxygen concentration is mainly controlled by hypoxia-inducible transcription factors (HIFs). Besides regulation of hypoxia-responsible gene expression, HIF-3α has recently been shown to be involved in lung development and in the metabolic process of fat tissue. However, the precise mechanism for such properties of HIF-3α is still largely unknown. To this end, we generated HIF3A gene-disrupted mice by means of genome editing technology to explore the pleiotropic role of HIF-3α in development and physiology. We obtained adult mice carrying homozygous HIF3A gene mutations with comparable body weight and height to wild-type mice. However, the number of litters and ratio of homozygous mutation carriers born from the mating between homozygous mutant mice was lower than expected due to sporadic deaths on postnatal day 1. HIF3A gene-disrupted mice exhibited abnormal configuration of the lung such as a reduced number of alveoli and thickened alveolar walls. Transcriptome analysis showed, as well as genes associated with lung development, an upregulation of stearoyl-Coenzyme A desaturase 1, a pivotal enzyme for fatty acid metabolism. Analysis of fatty acid composition in the lung employing gas chromatography indicated an elevation in palmitoleic acid and a reduction in oleic acid, suggesting an imbalance in distribution of fatty acid, a constituent of lung surfactant. Accordingly, administration of glucocorticoid injections during pregnancy resulted in a restoration of normal alveolar counts and a decrease in neonatal mortality. In conclusion, these observations provide novel insights into a pivotal role of HIF-3α in the preservation of critically important structure and function of alveoli beyond the regulation of hypoxia-mediated gene expression. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Transcriptional profiling of Toll-like receptor 2-deficient primary murine brain cells during Toxoplasma gondii infection." The correction states that Figures 3E and 3F, as well as Figures 4E and 4F, were swapped in the original article. The corrected figures are provided in the notice. The article compares the transcriptional profiles of Tlr2-/- and wild-type neurons and macrophages during T. gondii infection, identifying upregulated and downregulated genes. The authors also performed GO term enrichment analysis to explore the function of these genes. The correction notice was reported by multiple authors. [Extracted from the article]

Background: Analysis of omics data that contain multidimensional biological and clinical information can be complex and make it difficult to deduce significance of specific biomarker factors. Methods: We explored the utility of propensity score matching (PSM), a statistical technique for minimizing confounding factors and simplifying the examination of specific factors. We tested two datasets generated from cohorts of colorectal cancer (CRC) patients, one comprised of immunohistochemical analysis of 12 protein markers in 544 CRC tissues and another consisting of RNA-seq profiles of 163 CRC cases. We examined the efficiency of PSM by comparing pre- and post-PSM analytical results. Results: Unlike conventional analysis which typically compares randomized cohorts of cancer and normal tissues, PSM enabled direct comparison between patient characteristics uncovering new prognostic biomarkers. By creating optimally matched groups to minimize confounding effects, our study demonstrates that PSM enables robust extraction of significant biomarkers while requiring fewer cancer cases and smaller overall patient cohorts. Conclusion: PSM may emerge as an efficient and cost-effective strategy for multiomic data analysis and clinical trial design for biomarker discovery. [ABSTRACT FROM AUTHOR]

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption. [ABSTRACT FROM AUTHOR]

Introduction: Religious leaders have the potential to play a significant role in the identification and referral of individuals with mental health problems. Objective: This study sought to understand the perceptions of religious leaders in regards to identifying and referring parishioners with mental health issues to healthcare professionals, in Chimbote, Peru. Methods: We performed a cross-sectional study that covered religious leaders of different religious groups in Chimbote. The leaders completed a survey that assessed their characteristics, past experiences of detecting and referring those with mental health problems to healthcare professionals, and perceptions of four clinical cases (for which we used the Clergy's Perception of Mental Illness Survey instrument). Results: We included 109 religious' leaders of four religious groups (11 Catholics, 70 Evangelicals, 21 Mormons, and 7 Adventists). Of these, 50.5% had received at least one request for help with mental health issues from a parishioner in the previous month, over 85% expressed a desire for training in identifying mental health problems, and 22–30% reported receiving any training. While the majority of leaders were able to correctly identify cases of depression, alcohol dependence, and drug problems, only 62% correctly classified a case of schizophrenia. Despite this, 80% stated that they would refer their parishioners to healthcare professionals. Conclusion: Parishioners tend to consult their religious leaders regarding their mental health and approximately 80% stated they would refer such cases to a healthcare professional. However, less than one-third of the leaders had received training to detect mental health problems. These results suggest that there is a need for training programs to improve the ability of religious leaders to identify and refer individuals with mental health issues. [ABSTRACT FROM AUTHOR]

Background: Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study. Methods: Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20). Results: The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group. Conclusions: Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

The purpose is to clarify the relationship between patients with retinal vein occlusion (RVO), maximal intima-media complex thickness (Max IMT), and N-terminal pro-brain natriuretic peptide (NT-proBNP), which is useful in assessing atherosclerosis. This was a retrospective observation, single center study. The patients were 86 RVO patients (male: female = 43:43, mean age 63.3 years), 25 with central retinal vein occlusion (CRVO) and 61 with branch retinal vein occlusion (BRVO), classified as ≧50 years old and <50 years old, Max IMT≧1.1 and less, NT-pro BNP≧55 and less. Results showed that Max IMT ≧1.1 was significantly more common in both the CRVO and BRVO groups at ≧50 years, and NT-pro BNP ≧55 was significantly more common in the CRVO group. Max IMT≧1.1 was seen in 80% of the BRVO group and in 85% of patients aged ≧50 years. Sixty-eight percent of patients in the CRVO group had Max IMT≧1.1, but none of those < 50 years had Max IMT≧1.1. Forty-eight percent of RVO patients had NT-pro BNP≧55, and significantly more patients had Max IMT≧1.1 than those who did not have NT-pro BNP more than 55 (p = 0.02). Multiple regression analysis with Max IMT as the dependent variable showed that age and NT-pro BNP were significantly associated with RVO (p = 0.015, 0.022). RVO patients were more likely to have a Max IMT≧1.1, which was associated with atherosclerosis. Max IMT and NT-pro BNP were also associated with RVO patients, so NT-pro BNP may be a marker of RVO. [ABSTRACT FROM AUTHOR]

Humans naturally associate stimulus features of one sensory modality with those of other modalities, such as associating bright light with high-pitched tones. This phenomenon is called crossmodal correspondence and is found between various stimulus features, and has been suggested to be categorized into several types. However, it is not yet clear whether there are differences in the underlying mechanism between the different kinds of correspondences. This study used exploratory factor analysis to address this question. Through an online experiment platform, we asked Japanese adult participants (Experiment 1: N = 178, Experiment 2: N = 160) to rate the degree of correspondence between two auditory and five visual features. The results of two experiments revealed that two factors underlie the subjective judgments of the audiovisual crossmodal correspondences: One factor was composed of correspondences whose auditory and visual features can be expressed in common Japanese terms, such as the loudness–size and pitch–vertical position correspondences, and another factor was composed of correspondences whose features have no linguistic similarities, such as pitch–brightness and pitch–shape correspondences. These results confirm that there are at least two types of crossmodal correspondences that are likely to differ in terms of language mediation. [ABSTRACT FROM AUTHOR]

Phacoemulsification has emerged as the global standard for cataract surgery, and various novel methods, tools, and agents have promoted surgical efficiency and reduced complications. Conventionally, the phaco tip, which cleaves and aspirates the cataractous lens, has been mainly constructed of metal. In this study, the risk of anterior capsule rupture was evaluated under conditions of different power modes, longitudinal (Mode-L), torsional (Mode-T), or both (Mode-LT), and different aspiration powers (0 or 200 mmHg), using a traditional metal phaco tip (Group-M) or a new phaco tip with a high-strength polymer overmold on the needle edge (Group-P), which was developed to reduce the risk of capsule rupture. One hundred twenty porcine eyes were used for experiments within a setting of typical human physiological intraocular pressure. We found that Group-M showed capsule rupture with a smaller ultrasound power than did Group-P, regardless of power mode or aspiration power. In Group-M, there was no significant difference in risk of capsule rupture among power modes, however in Group-P, capsule rupture was least likely to occur with Mode-T. These results provide useful information for inexperienced ophthalmologists to improve surgical safety. [ABSTRACT FROM AUTHOR]

In the Japanese hagfish, Eptatretus burgeri, approximately 21% of the genomic DNA in germ cells (2n = 52) consists of 16 chromosomes (eliminated [E]-chromosomes) that are eliminated from presumptive somatic cells (2n = 36). To uncover the eliminated genome (E-genome), we have identified 16 eliminated repetitive DNA families from eight hagfish species, with 11 of these repeats being selectively amplified in the germline genome of E. burgeri. Furthermore, we have demonstrated that six of these sequences, namely EEEb1–6, are exclusively localized on all 16 E-chromosomes. This has led to the hypothesis that the eight pairs of E-chromosomes are derived from one pair of ancestral chromosomes via multiple duplication events over a prolonged evolutionary period. NGS analysis has recently facilitated the re-assembly of two distinct draft genomes of E. burgeri, derived from the testis and liver. This advancement allows for the prediction of not only nonrepetitive eliminated sequences but also over 100 repetitive and eliminated sequences, accomplished through K-mer-based analysis. In this study, we report four novel eliminated repetitive DNA sequences (designated as EEEb7–10) and confirm the relative chromosomal localization of all eliminated repeats (EEEb1–10) by fluorescence in situ hybridization (FISH). With the exception of EEEb10, all sequences were exclusively detected on EEEb1-positive chromosomes. Surprisingly, EEEb10 was detected as an intense signal on EEEb1-positive chromosomes and as a scattered signal on other chromosomes in germ cells. The study further divided the eight pairs of E-chromosomes into six groups based on the signal distribution of each DNA family, and fiber-FISH experiments showed that the EEEb2–10 family was dispersed in the EEEb1-positive extended chromatin fiber. These findings provide new insights into the mechanisms underlying chromosome elimination and the evolution of E-chromosomes, supporting our previous hypothesis. [ABSTRACT FROM AUTHOR]

Efficient body movement is required in our daily lives, as it facilitates responding to the external environment and producing movements in various directions and distances. While numerous studies have reported on goal-directed movements in the frontal direction during gait initiation, there is limited research on the efficient movement of the lower limbs in multiple directions and distances. Therefore, we aimed to examine changes in the kinematics of lower-limb reaching movements to determine skilled motor ability in terms of direction and distance. Sixteen adults (10 male participants) were requested to reach targets projected on the floor in seven directions and at three distances for a total of 21 points. The reaching time slowed down for the contralateral side (right foot to left-sided target) and was caused by a slower start of the toe movement. To identify the cause of this delay, we analyzed the onset of movement at each joint and found that movement to the contralateral side starts from the hip, followed by the knee, and subsequently the toe. The time-to-peak velocity was also calculated, and the motion required to reach the target in the shortest time varied depending on direction and distance. These results suggested that movement kinematics vary with direction and distance, resulting in a slower reaching time on the contralateral side. The results of our study hold promise for potential applications in sports and rehabilitation. [ABSTRACT FROM AUTHOR]

Environmental factors affect the growth of microorganisms and therefore alter the composition of microbiota. Correlative analysis of the relationship between metagenomic composition and the environmental gradient can help elucidate key environmental factors and establishment principles for microbial communities. However, a reasonable method to quantitatively compare whole metagenomic data and identify the primary environmental factors for the establishment of microbiota has not been reported so far. In this study, we developed a method to compare whole proteomes deduced from metagenomic shotgun sequencing data, and quantitatively display their phylogenetic relationships as metagenomic trees. We called this method Metagenomic Phylogeny by Average Sequence Similarity (MPASS). We also compared one of the metagenomic trees with dendrograms of environmental factors using a comparison tool for phylogenetic trees. The MPASS method correctly constructed metagenomic trees of simulated metagenomes and soil and water samples. The topology of the metagenomic tree of samples from the Kirishima hot springs area in Japan was highly similarity to that of the dendrograms based on previously reported environmental factors for this area. The topology of the metagenomic tree also reflected the dynamics of microbiota at the taxonomic and functional levels. Our results strongly suggest that MPASS can successfully classify metagenomic shotgun sequencing data based on the similarity of whole protein-coding sequences, and will be useful for the identification of principal environmental factors for the establishment of microbial communities. Custom Perl script for the MPASS pipeline is available at https://github.com/s0sat/MPASS. [ABSTRACT FROM AUTHOR]

Background: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME). Methods: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining. Results: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively). Conclusions: High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS. [ABSTRACT FROM AUTHOR]

Facial expressions are widely recognized as universal indicators of underlying internal states in most species of animals, thereby presenting as a non-invasive measure for assessing physical and mental conditions. Despite the advancement of artificial intelligence-assisted tools for automated analysis of voluminous facial expression data in human subjects, the corresponding tools for mice still remain limited so far. Considering that mice are the most prevalent model animals for studying human health and diseases, a comprehensive characterization of emotion-dependent patterns of facial expressions in mice could extend our knowledge on the basis of emotions and the related disorders. Here, we present a framework for the development of a deep learning-powered tool for classifying facial expressions in head-fixed mouse. We demonstrate that our machine vision was capable of accurately classifying three different emotional states from lateral facial images in head-fixed mouse. Moreover, we objectively determined how our classifier characterized the differences among the facial images through the use of an interpretation technique called Gradient-weighted Class Activation Mapping. Importantly, our machine vision presumably discerned the data by leveraging multiple facial features. Our approach is likely to facilitate the non-invasive decoding of a variety of emotions from facial images in head-fixed mice. [ABSTRACT FROM AUTHOR]

A non-thermal atmospheric pressure plasma jet (APPJ) may stimulate cells and tissues or result in cell death depending on the intensity of plasma at the target; therefore, we herein investigated the effects of non-thermal plasma under non-contact conditions on the healing of full-thickness wounds in diabetic mice (DM+ group) and normal mice (DM- group). A hydrogen peroxide colorimetric method and high performance liquid chromatography showed that APPJ produced low amounts of reactive oxygen and nitrogen species. Ten-week-old male C57BL/6j mice with normal blood glucose levels (DM- group) and 10-week-old male C57BLKS/J Iar-+Leprdb/+Leprdb mice (DM+ group) received two full-thickness cutaneous wounds (4 mm in diameter) on both sides of the dorsum. Wounds were treated with or without the plasma jet or argon gas for 1 minute and were then covered with a hydrocolloid dressing (Hydrocolloid), according to which mice were divided into the following groups: DM+Plasma, DM+Argon, DM+Hydrocolloid, DM-Plasma, DM-Argon, and DM-Hydrocolloid. Exudate weights, wound areas, and wound area ratios were recorded every day. Hematoxylin and eosin staining was performed to assess re-epithelialization and α-SMA immunohistological staining to evaluate the formation of new blood vessels. Non-thermal plasma under non-contact conditions reduced the production of exudate. Exudate weights were smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups. The wound area ratio was smaller for plasma-treated wounds, and was also smaller in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups on days 1–21 (p<0.01). Wound areas were smaller in the DM-Plasma group than in the DM-Argon group until day 14 and differences were significant on days 1–5 (p<0.01). The percentage of re-epithelialization was significantly higher in the DM+Plasma group than in the DM+Argon and DM+Hydrocolloid groups (p<0.01). The number of new blood vessels that had formed by day 7 was significantly higher in the DM+Plasma group than in the DM+Hydrocolloid and DM+Argon groups (p<0.05). These results indicate that treatment with the current non-thermal plasma APPJ device under non-contact conditions accelerated wound healing in diabetic mice. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is a staple food of Madagascar, where per capita rice consumption is among the highest worldwide. Rice in Madagascar is mainly grown on smallholder farms on soils with low fertility and in the absence of external inputs such as mineral fertilizers. Consequently, rice productivity remains low and the gap between rice production and consumption is widening at the national level. This study evaluates genetic resources imported from the IRRI rice gene bank to identify potential donors and loci associated with low soil fertility tolerance (LFT) that could be utilized in improving rice yield under local cultivation conditions. Accessions were grown on-farm without fertilizer inputs in the central highlands of Madagascar. A Genome-wide association study (GWAS) identified quantitative trait loci (QTL) for total panicle weight per plant, straw weight, total plant biomass, heading date and plant height. We detected loci at locations of known major genes for heading date (hd1) and plant height (sd1), confirming the validity of GWAS procedures. Two QTLs for total panicle weight were detected on chromosomes 5 (qLFT5) and 11 (qLFT11) and superior panicle weight was conferred by minor alleles. Further phenotyping under P and N deficiency suggested qLFT11 to be related to preferential resource allocation to root growth under nutrient deficiency. A donor (IRIS 313–11949) carrying both minor advantageous alleles was identified and crossed to a local variety (X265) lacking these alleles to initiate variety development through a combination of marker-assisted selection with selection on-farm in the target environment rather than on-station as typically practiced. [ABSTRACT FROM AUTHOR]

Purpureocillium lilacinum is a biocontrol Ascomycota fungus against various plant pathogens. In the present study, the efficacy of P. lilacinum was evaluated against a root-knot nematode, Meloidogyne incognita that infects eggplants. We performed an in vitro experiment in which the direct effects of P. lilacinum on the second-stage juvenile survival and egg hatching of M. incognita were tested at different exposure times. The results showed that P. lilacinum significantly reduced the rates of egg hatching and juvenile survival in a dose-dependent manner. Microscopic observation demonstrated that P. lilacinum directly penetrated the eggs and contacted the juveniles, indicating how P. lilacinum parasitizes M. incognita. We also performed a pot assay in which soil-grown eggplants were treated with P. lilacinum followed by inoculation with M. incognita. The results indicated that P. lilacinum effectively reduced the nematode population and the number of galls in plant roots. Interestingly, application of P. lilacinum resulted in significant enhancements in plant growth and biomass, even under nematode infection, while it improved plant photosynthetic pigments, i.e., chlorophyll and carotenoids. Taken together, our study suggested that P. lilacinum can be used as a plant growth-promoting fungus and a biological nematicide for disease management of root-knot nematodes in eggplants. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease affects hundreds of millions of people worldwide and is one of the most common causes for visits to eye care practitioners. The fluorescein tear breakup time test is currently widely used to diagnose dry eye disease, but it is an invasive and subjective method, thus resulting in variability in diagnostic results. This study aimed to develop an objective method to detect tear breakup using the convolutional neural networks on the tear film images taken by the non-invasive device KOWA DR-1α. Methods: The image classification models for detecting characteristics of tear film images were constructed using transfer learning of the pre-trained ResNet50 model. The models were trained using a total of 9,089 image patches extracted from video data of 350 eyes of 178 subjects taken by the KOWA DR-1α. The trained models were evaluated based on the classification results for each class and overall accuracy of the test data in the six-fold cross validation. The performance of the tear breakup detection method using the models was evaluated by calculating the area under curve (AUC) of receiver operating characteristic, sensitivity, and specificity using the detection results of 13,471 frame images with breakup presence/absence labels. Results: The performance of the trained models was 92.3%, 83.4%, and 95.2% for accuracy, sensitivity, and specificity, respectively in classifying the test data into the tear breakup or non-breakup group. Our method using the trained models achieved an AUC of 0.898, a sensitivity of 84.3%, and a specificity of 83.3% in detecting tear breakup for a frame image. Conclusions: We were able to develop a method to detect tear breakup on images taken by the KOWA DR-1α. This method could be applied to the clinical use of non-invasive and objective tear breakup time test. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sjögren's disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, in vitro and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high LAMP3 mRNA expression in minor salivary glands and those with LAMP3 mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high LAMP3 expression compared those with normal LAMP3 expression. Taken together, these findings suggested that by determining salivary gland LAMP3 mRNA level, a patient's response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD. [ABSTRACT FROM AUTHOR]

Although main pancreatic duct dilatation and pancreatic cysts are risk factors for developing pancreatic cancer, limited data exist regarding these findings in relatives and spouses of pancreatic cancer patients. The frequency of these findings was examined using long-term follow-up data and transabdominal ultrasonography focusing on the pancreas. We prospectively enrolled 184 relatives and spouses of pancreatic cancer patients and performed special pancreatic ultrasonography to detect main pancreatic duct dilatation and pancreatic cysts. First-degree relatives (148 participants) of patients with pancreatic cancer were significantly younger than the spouses (36 participants; 41 vs. 65 years old). The frequency of ultrasonographic findings was significantly different between the relative (8.8%) and spouse (33.3%) groups. Main pancreatic duct dilatation and pancreatic cysts were observed in seven (4.7%) and seven (4.7%) participants in the relative group, and in nine (25.0%) and five (13.9%) participants in the spouse group, respectively. On multivariate analysis, age was an independent risk factor for the ultrasonographic findings. The frequency of ultrasonographic findings was significantly higher in spouses than in first-degree relatives of patients with pancreatic cancer and was strongly influenced by the age gap between the groups. Main pancreatic duct dilatation was frequently observed, especially in the spouse group. [ABSTRACT FROM AUTHOR]

Background: Autonomic dysfunction is a factor in irritable bowel syndrome (IBS). However, there are no reports of autonomic nervous system (ANS) activity during natural defecation in patients with IBS. We aimed to clarify the relationship between ANS activity and life events, such as defecation and abdominal symptoms, using real-time recording. Methods: Six patients with IBS and 14 healthy controls were enrolled in this prospective multicenter study. ANS activity was recorded for 24 h using a T-shirt wearable device, and life events were recorded simultaneously in real time using a smartphone application software. Low frequency/high frequency (LF/HF) and HF calculated by power spectrum analysis were defined as activity indicators of the sympathetic and parasympathetic nerves, respectively. Results: The means of LF/HF and HF in the period with positive symptoms were comparable between the groups; however, the sum of LF/HF, sum of ΔLF/HF, and the maximum variation in ΔLF/HF were significantly higher in the IBS group. In the IBS group, the sum of ΔLF/HF and LF/HF increased significantly from 2 min before defecation, and the sum of LF/HF remained significantly higher until 9 min after defecation. The sum of ΔLF/HF at 2 min before defecation was significantly positively correlated with the intensity of abdominal pain and diarrhea and constipation scores. In contrast, it was significantly negatively correlated with defecation satisfaction and health-related quality of life. Conclusions: In patients with IBS, sympathetic nerve activity was activated 2 min before defecation, which was correlated with abdominal symptoms and lower QOL. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. Methods: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Results: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. Conclusions: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the age-related change in color visual acuity (CVA) in normal eyes. Methods: In total, 162 normal eyes (162 subjects, women: 52, men: 110, age range: 15–68 years) with best-corrected visual acuity (BCVA) ≥20/13 were enrolled. Fifteen colors from the New Color Test (chroma 6) were applied to Landolt "C" rings, white point D65 was applied as background, and a luminance of 30 cd/m2 was set for both the rings and the background. These rings were used to measure the chromatic spatial discrimination acuity as the CVA value, while changing the stimulus size. Correlations of the CVA value of each color and age were evaluated. Mean CVA values of all 15 colors (logarithm of the minimum angle of resolution) were compared between age groups in 10-year increments. Results: Nine CVA values (red, yellow-red, red-yellow, green, blue-green, green-blue, purple, red-purple, and purple-red) were negatively correlated with age (all p<0.05); the remaining six (yellow, green-yellow, yellow-green, blue, purple-blue, and blue-purple), as well as BCVA were not. The age groups with the best to worst mean CVA values of 15 colors were as follows: 20–29 (mean ± standard deviation, 0.303 ± 0.113), 30–39 (0.324 ± 0.096), 10–19 (0.333 ± 0.022), 50–59 (0.335 ± 0.078), 40–49 (0.339 ± 0.096), and 60–69 (0.379 ± 0.125) years. There were statistically significant differences between mean CVA values of the following groups: 20–29 and 40–49 years; 20–29 and 60–69 years; 30–39 and 60–69 years (all p<0.01). Conclusions: The CVA values related to the medium/long-wavelength-sensitive cones were more susceptible to aging than those related to the short-wavelength-sensitive cones. This differed from previous reports, and may be related to the difference in the range of foveal cone function evaluated with each examination. [ABSTRACT FROM AUTHOR]

Yokukansan (YKS) is a traditional Japanese herbal (Kampo) medicine prescribed for anxiety. In this randomized controlled trial, we compared the subjective assessment of anxiety using questionnaires and its objective assessment using salivary alpha-amylase concentrations in YKS and control (CNT) groups of women undergoing breast surgery. The trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (registration number: UMIN000028998), and the investigators were blinded to drug administration. One hundred patients who underwent breast cancer surgery were allocated to either the YKS or the CNT group. Finally, 35 and 42 patients in the YKS and CNT groups were analyzed, respectively. The YKS group received two 2.5 g doses of the medication before sleeping on the night before surgery and 2 h before inducing anesthesia, while the CNT group did not receive medication preoperatively. Patients answered two questionnaires, the Hospital Anxiety and Depression Scale and the State-Trait Anxiety Inventory, pre-and postoperatively as subjective anxiety assessments. As an objective anxiety indicator, salivary alpha-amylase levels were measured the day before, directly before, and the day after surgery (T3). In the YKS group, salivary alpha-amylase scores directly before operation were significantly lower than those on the day before surgery and at one day postoperatively (F [2,150] = 3.76, p = 0.03). Moreover, the Hospital Anxiety and Depression Scale-Anxiety and State-Trait Anxiety Inventory-Trait scores were significantly more improved postoperatively in the YKS group than in the CNT group (difference in Hospital Anxiety and Depression Scale-Anxiety: YKS, mean -2.77, 95% confidence interval [-1.48 –-4.06], p <0.001, and CNT, -1.43 [-0.25–-2.61], p = 0.011; and difference in State-Trait Anxiety Inventory: YKS group, -4.23 [-6.95–-1.51], p = 0.0004; and CNT group, 0.12 [-2.36–2.60], p = 0.92). No side effects were associated with YKS. YKS may reduce perioperative anxiety in patients undergoing surface surgery. [ABSTRACT FROM AUTHOR]

Background: The bronchoalveolar lavage (BAL) recovery rate should generally be more than 30% for effective diagnosis. However, there have been no reports investigating a target bronchus for BAL, and the cause of BAL recovery failure is uncertain. Therefore, this study detected predictive factors for BAL recovery failure through investigations on a target bronchus for BAL by using a 3D image analysis system. Therefore, this study detected predictive factors for BAL recovery failure. Materials and methods: We retrospectively collected data from 338 adult patients who underwent BAL procedures at Fukujuji Hospital from June 2018-March 2022. Factors correlated with the BAL recovery rate were detected. Furthermore, the patients were divided into the failure group (recovery rate <30%; 36 patients) and the success group (recovery rate ≥30%; 302 patients), and data were compared between the two groups by analysing the target bronchus by using a 3D image analysis system. Results: The patients in the failure group were older (median 74.5 years old [IQR 68.0–79.0] vs. median 70.0 years old [IQR 59.0–76.0], p = 0.016), more likely to be male (n = 27 [75.0%] vs. n = 172 [57.0%], p = 0.048), more likely to have COPD (n = 7 [19.4%] vs. n = 14 [4.6%], p = 0.003), and more likely to perform a target site of BAL other than the middle/lingual lobe (n = 11 [30.5%] vs. n = 35 [11.6%], p = 0.004) than those in the success group. The area of the bronchial wall was positively related to the recovery rate (r = 0.141, p = 0.009), and the area of the bronchial wall in the failure group was lower than that in the success group (median 10.5 mm2 [interquartile range (IQR) 8.1–14.6] vs. median 14.5 mm2 [11.4–19.0], p<0.001). Conclusion: The study shows that a thin bronchial wall, COPD, and a target site of BAL other than the middle/lingual lobe were identified as the predicted factors for BAL recovery failure. The weakness of the bronchial wall might cause bronchial collapse during the BAL procedure. [ABSTRACT FROM AUTHOR]

Background: High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). Methods: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin≥ 2N or aspartate aminotransferase/alanine aminotransferase concentrations ≥ 2N. Short-term and one-year prognostic outcomes were prospectively assessed. Results: A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Conclusion: Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by a recently identified virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease is a pandemic. Although the hallmarks of severe COVID-19 have been established, the underlying mechanisms that promote severe pathology have not been thoroughly studied. A better understanding of the immune response in severe COVID-19 patients may help guide the development of therapeutic strategies and predict immuno-pathogenicity. This study was set to determine the lymphocyte and cytokine profiles associated with COVID-19 severity. A total of 43 hospitalised COVID-19 patients were recruited for the study and whole blood samples were drawn from each patient. Complete blood counts, lymphocyte subset profiles and C-reactive protein statuses of patients were determined. Cytometric bead array was performed to analyse the cytokine profiles of each patient. The demographic characteristics showed that the median age of the patients was 48.72 years, with an interquartile range from 40 to 60 years, and 69.77% of the patients were male. COVID-19 patients exhibited significantly low CD4+ lymphocyte expansion and leucocytosis augmented by elevated neutrophil and immature granulocytes. Stratification analysis revealed that reduced monocytes and elevated basophils and immature granulocytes are implicated in severe pathology. Additionally, cytokine results were noted to have significant incidences of interleukin 17A (IL-17A) expression associated with severe disease. Results from this study suggest that a systemic neutrophilic environment may preferentially skew CD4+ lymphocytes towards T-helper 17 and IL-17A promotion, thus, aggravating inflammation. Consequently, results from this study suggest broad activity immunomodulation and targeting neutrophils and blocking IL-17 production as therapeutic strategies against severe COVID-19. [ABSTRACT FROM AUTHOR]

Studies have presented data regarding the effects of short-term (weeks) and long-term (one year) use of standing desks in classrooms on children's health, cognition, and musculoskeletal symptoms. However, no previous study has examined such effects in an extremely short-term period such as one classroom lesson. This study aimed to examine the effects of using standing desks for 45 minutes on elementary school students' stress and executive function. For this experiment, 56 students were recruited from public elementary schools in Setagayaku, Tokyo, Japan. There were three conditions involving the use of standing desks (standing, sitting, and mixed), and all students performed tasks for 45 minutes in each condition. Measurements of stress and executive function were performed before and after the students engaged with each condition. Stress levels did not differ between the sitting and standing conditions for the full 45 minutes. The number of correct answers in the Stroop test, an interference task, was higher in the standing and mixed conditions (switching between standing and sitting) than in the sitting condition (interaction: F(1,37) = 3.340, p = 0.04, η2 = 0.05). These results indicate that using standing desks for 45 minutes improved the 'inhibition' of executive function without excessively increasing stress levels. [ABSTRACT FROM AUTHOR]

Adverse effects of morphine on locomotor function after moderate to severe spinal cord injury (SCI) have been reported; however, the effects after mild SCI without damage of lumbar α-motoneurons have not been investigated. We investigated the effects of lumbar intrathecal morphine on locomotor function after mild thoracic SCI and the involvement of classic opioid receptor activation. A mild thoracic contusive SCI was induced in adult rats at the T9-T10 spine level under sevoflurane anesthesia. We evaluated the effects of single doses of intrathecal morphine and selective μ-, δ-, and κ-opioid receptor agonists, continuous infusion of intrathecal morphine for 72 hours, and administration of physiological saline on locomotor function and muscle tone in the hindlimbs. The numbers of damaged and total α-motoneurons in the lumbar spinal cord were also investigated. Single doses of morphine aggravated residual locomotor function after SCI but did not affect functional recovery. Single doses of morphine and μ- and δ-opioid receptor agonists significantly aggravated residual locomotor function with increases in muscle tone after SCI, and the effects of the drugs were reversed by naloxone. In contrast, continuous infusion of morphine led to persistent decline in locomotor function with increased muscle tone, which was not reversed by naloxone, but did not increase the number of damaged lumbar α-motoneurons. These results indicate that a single dose of morphine at an analgesic dose transiently increases muscle tone of the hindlimbs via activation of spinal μ- and δ- opioid receptors, resulting in further deterioration of locomotor function in the acute phase of mild SCI. Our results also suggest that an increased dose of morphine with prolonged administration leads to persistent decline in locomotor function with increased muscle tone via mechanisms other than direct activation of classical opioid receptors. Morphine should be used cautiously even after mild SCI. [ABSTRACT FROM AUTHOR]

Objectives: The accurate prevalence of acquired immunodeficiency syndrome (AIDS)-defining illnesses (ADIs) in human immunodeficiency virus (HIV)-infected patients has not been well investigated. Hence, a longitudinal nationwide surveillance study analyzing the current status and national trend of opportunistic complications in HIV-infected patients in Japan is warranted. Methods: A nationwide surveillance of opportunistic complications in HIV-infected patients from 1995 to 2017 in Japan was conducted. An annual questionnaire was sent to 383 HIV/AIDS referral hospitals across Japan to collect information (CD4+ lymphocyte count, time of onset, outcome, and antiretroviral therapy [ART] status) of patients diagnosed with any of 23 ADIs between 1995 and 2017. Results: The response and case capture rates of the questionnaires in 2017 were 53% and 76%, respectively. The number of reported cases of opportunistic complications peaked in 2011 and subsequently declined. Pneumocystis pneumonia (38.7%), cytomegalovirus infection (13.6%), and candidiasis (12.8%) were associated with the cumulative incidence of ADIs between 1995 and 2017. The mortality rate in HIV-infected patients with opportunistic complications substantially decreased to 3.6% in 2017. The mortality rate was significantly higher in HIV patients who received ART within 14 days of diagnosis of complications than in those who received ART 15 days after diagnosis (13.0% vs. 3.2%, p < 0.01). Conclusions: We have demonstrated a 23-year trend of a newly diagnosed AIDS status in Japan with high accuracy. The current data reveal the importance of Pneumocystis pneumonia as a first-onset illness and that early initiation of ART results in poor outcomes in HIV patients in Japan. [ABSTRACT FROM AUTHOR]

Respiratory infectious diseases pose a serious threat worldwide, and novel antiviral materials are highly demanded. Photocatalytic nanoparticles have been developed to inhibit indirect transmission of pathogens by acting as surface coating materials. During development of such antiviral materials, researchers use bacteriophages as model viruses due to their safety and experimental efficiency. Screening methods are used to identify potential antiviral materials, and better screening technologies will accelerate the discovery of antiviral treatments. In this study, we constructed a novel platform to evaluate antiviral activity of surface coating materials using the M13 bacteriophage and phagemid system derived from phage display technology. The evaluation results generated by this system for the two tested antiviral materials were comparable to those for the materials tested on the Qβ bacteriophage and influenza virus using traditional screening methods. The experimental system developed in this study provides rapid and effective screening and can be applied to the development of novel antiviral materials. [ABSTRACT FROM AUTHOR]

We recently reported increased levels of urinary free-glycans in some cancer patients. Here, we focused on cancer related alterations in the levels of high molecular weight freeglycans. The rationale for this study was that branching, elongation, fucosylation and sialylation, which lead to increases in the molecular weight of glycans, are known to be up-regulated in cancer. Urine samples from patients with gastric cancer, pancreatic cancer, cholangiocarcinoma and colorectal cancer and normal controls were analyzed. The extracted free-glycans were fluorescently labeled with 2-aminopyridine and analyzed by multi-step liquid chromatography. Comparison of the glycan profiles revealed increased levels of glycans in some cancer patients. Structural analysis of the glycans was carried out by performing chromatography and mass spectrometry together with enzymatic or chemical treatments. To compare glycan levels between samples with high sensitivity and selectivity, simultaneous measurements by reversed-phase liquid chromatography-selected ion monitoring of mass spectrometry were also performed. As a result, three lactose-core glycans and 78 free-N-glycans (one phosphorylated oligomannose-type, four sialylated hybrid-type and 73 bi-, tri- and tetra-antennary complex-type structures) were identified. Among them, glycans with a1,3-fucosylation ((+/- sialyl) Lewis X), triply a2,6-sialylated tri-antennary structures and/or a (Man3)GlcNAc1-core displayed elevated levels in cancer patients. However, simple a2,3-sialylation and a1,6-core-fucosylation did not appear to contribute to the observed increase in the level of glycans. Interestingly, one tri-antennary free-N-glycan that showed remarkable elevation in some cancer patients contained a unique Glcß1-4GlcNAccore instead of the common GlcNAc2-core at the reducing end. This study provides further insights into free-glycans as potential tumor markers and their processing pathways in cancer. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that chronic kidney disease is associated with cardiovascular disease, dementia, and frailty, all of which cause disability and early death. We investigated whether increased activity of urinary N-acetyl-β-glucosaminidase (NAG), a marker of kidney injury, is associated with risk of disability or all-cause mortality in a general population. Methods: Follow-up data from the Hidaka Cohort Study, a population-based cohort study of members of a Japanese rural community, were obtained via questionnaires completed by participants or their relatives. Multivariable analyses were used to investigate relations between urinary NAG activity–urinary creatinine concentration ratio and risk of disability or all-cause mortality. Results: A total of 1182 participants were followed up for a median of 12.4 years. The endpoints were receipt of support under the public long-term care insurance program, and all-cause mortality. A total of 122 participants (10.3%) were reported to be receiving long-term care and 230 (19.5%) had died. After adjustment for cardiovascular risk factors along with physical activity, and using the quartile 1 results as a reference, the odds ratio (OR) for disability was 2.12 [95% confidence interval (95% confidence interval [CI]), 1.04–4.33; p = 0.038) and the hazard ratio (HR) for all-cause mortality was 1.65 (95% CI, 1.05–2.62; p = 0.031) in participants with urinary NAG/creatinine ratio in quartile 4. Similar results were obtained in participants without proteinuria: OR for disability, 2.46 (95% CI, 1.18–5.16; p = 0.017); and HR for all-cause mortality, 1.62 (95% CI, 1.00–2.63; p = 0.049). Conclusions: Increased urinary NAG/creatinine ratio was associated with risk of disability or all-cause mortality in a general population. [ABSTRACT FROM AUTHOR]

The effects of muscle weakness on speech are currently not fully known. We investigated the relationships between maximum tongue pressure and second formant transition in adults with different types of dysarthria. It focused on the slope in the second formant transition because it reflects the tongue velocity during articulation. Sixty-three Japanese speakers with dysarthria (median age, 68 years; interquartile range, 58–77 years; 44 men and 19 women) admitted to acute and convalescent hospitals were included. Thirty neurologically normal speakers aged 19–85 years (median age, 22 years; interquartile range, 21.0–23.8 years; 14 men and 16 women) were also included. The relationship between the maximum tongue pressure and speech function was evaluated using correlation analysis in the dysarthria group. Speech intelligibility, the oral diadochokinesis rate, and the second formant slope were based on the impaired speech index. More than half of the speakers had mild to moderate dysarthria. Speakers with dysarthria showed significantly lower maximum tongue pressure, speech intelligibility, oral diadochokinesis rate, and second formant slope than neurologically normal speakers. Only the second formant slope was significantly correlated with the maximum tongue pressure (r = 0.368, p = 0.003). The relationship between the second formant slope and maximum tongue pressure showed a similar correlation in the analysis of subgroups divided by sex. The oral diadochokinesis rate, which is related to the speed of articulation, is affected by voice on/off, mandibular opening/closing, and range of motion. In contrast, the second formant slope was less affected by these factors. These results suggest that the maximum isometric tongue strength is associated with tongue movement speed during articulation. [ABSTRACT FROM AUTHOR]

Financial portfolio management (PM) is one of the most applicable problems in reinforcement learning (RL) owing to its sequential decision-making nature. However, existing RL-based approaches rarely focus on scalability or reusability to adapt to the ever-changing markets. These approaches are rigid and unscalable to accommodate the varying number of assets of portfolios and increasing need for heterogeneous data input. Also, RL agents in the existing systems are ad-hoc trained and hardly reusable for different portfolios. To confront the above problems, a modular design is desired for the systems to be compatible with reusable asset-dedicated agents. In this paper, we propose a multi-agent RL-based system for PM (MSPM). MSPM involves two types of asynchronously-updated modules: Evolving Agent Module (EAM) and Strategic Agent Module (SAM). An EAM is an information-generating module with a Deep Q-network (DQN) agent, and it receives heterogeneous data and generates signal-comprised information for a particular asset. An SAM is a decision-making module with a Proximal Policy Optimization (PPO) agent for portfolio optimization, and it connects to multiple EAMs to reallocate the corresponding assets in a financial portfolio. Once been trained, EAMs can be connected to any SAM at will, like assembling LEGO blocks. With its modularized architecture, the multi-step condensation of volatile market information, and the reusable design of EAM, MSPM simultaneously addresses the two challenges in RL-based PM: scalability and reusability. Experiments on 8-year U.S. stock market data prove the effectiveness of MSPM in profit accumulation by its outperformance over five different baselines in terms of accumulated rate of return (ARR), daily rate of return (DRR), and Sortino ratio (SR). MSPM improves ARR by at least 186.5% compared to constant rebalanced portfolio (CRP), a widely-used PM strategy. To validate the indispensability of EAM, we back-test and compare MSPMs on four different portfolios. EAM-enabled MSPMs improve ARR by at least 1341.8% compared to EAM-disabled MSPMs. [ABSTRACT FROM AUTHOR]

Cellular senescence is accompanied by metabolic and epigenomic remodeling, but the transcriptional mechanism of this process is unclear. Our previous RNA interference-based screen of chromatin factors found that lysine methyltransferases including SETD8 and NSD2 inhibited the senescence program in cultured fibroblasts. Here, we report that loss of the zinc finger and homeobox protein 3 (ZHX3), a ubiquitously expressed transcription repressor, induced senescence-associated gene expression and mitochondrial–nucleolar activation. Chromatin immunoprecipitation–sequencing analyses of growing cells revealed that ZHX3 was enriched at the transcription start sites of senescence-associated genes such as the cyclin-dependent kinase inhibitor (ARF-p16INK4a) gene and ribosomal RNA (rRNA) coding genes. ZHX3 expression was consistently downregulated in cells with replicative or oncogene-induced senescence. Mass spectrometry-based proteomics identified 28 proteins that interacted with ZHX3, including ATP citrate lyase and RNA metabolism proteins. Loss of ZHX3 or ZHX3-interaction partners by knockdown similarly induced the expression of p16INK4a and rRNA genes. Zhx3-knockout mice showed upregulation of p16INK4a in the testes, thymus and skeletal muscle tissues, together with relatively short survival periods in males. These data suggested that ZHX3 plays an essential role in transcriptional control to prevent cellular senescence. [ABSTRACT FROM AUTHOR]

Olfaction, one of the most important sensory systems governing insect behavior, is a possible target for pest management. Therefore, in this study, we analyzed the antennal transcriptome of the cowpea beetle, Callosobruchus maculatus (F.) (Coleoptera: Chrysomelidae: Bruchinae), which is a major pest of stored pulses and legumes. The de novo antennal RNA-seq assembly results identified 17 odorant, 2 gustatory, and 10 ionotropic receptors, 1 sensory neuron membrane protein, and 12 odorant-binding and 7 chemosensory proteins. Moreover, differential gene expression analysis of virgin male and female antennal samples followed by qRT-PCR revealed 1 upregulated and 4 downregulated odorant receptors in males. We also performed homology searches using the coding sequences built from previously proposed amino acid sequences derived from genomic data and identified additional chemosensory-related genes. [ABSTRACT FROM AUTHOR]

cAMP responsive element binding protein (CREB)-regulated transcription coactivators (CRTCs) regulate gene transcription in response to an increase in intracellular cAMP or Ca2+ levels. To date, three isoforms of CRTC have been identified in mammals. All CRTCs are widely expressed in various regions of the brain. Numerous studies have shown the importance of CREB and CRTC in energy homeostasis. In the brain, the paraventricular nucleus of the hypothalamus (PVH) plays a critical role in energy metabolism, and CRTC1 and CRTC2 are highly expressed in PVH neuronal cells. The single-minded homolog 1 gene (Sim1) is densely expressed in PVH neurons and in some areas of the amygdala neurons. To determine the role of CRTCs in PVH on energy metabolism, we generated mice that lacked CRTC1 and CRTC2 in Sim1 cells using Sim-1 cre mice. We found that Sim1 cell-specific CRTC1 and CRTC2 double-knockout mice were sensitive to high-fat diet (HFD)-induced obesity. Sim1 cell-specific CRTC1 and CRTC2 double knockout mice showed hyperphagia specifically for the HFD, but not for the normal chow diet, increased fat mass, and no change in energy expenditure. Interestingly, these phenotypes were stronger in female mice than in male mice, and a weak phenotype was observed in the normal chow diet. The lack of CRTC1 and CRTC2 in Sim1 cells changed the mRNA levels of some neuropeptides that regulate energy metabolism in female mice fed an HFD. Taken together, our findings suggest that CRTCs in Sim1 cells regulate gene expression and suppress excessive fat intake, especially in female mice. [ABSTRACT FROM AUTHOR]

Nivolumab, an immune checkpoint blocker, has been approved for advanced gastric cancer (GC), but predictive factors of nivolumab's efficacy in patients with GC, especially immune cells such as tissue-resident memory T cells or those forming tertiary lymphoid structures (TLS), remain unclear. Tissue samples were obtained from surgically resected specimens of patients with GC who were treated with nivolumab as third-line or later treatment. Immunohistochemical staining was performed to detect the presence of TLS and CD103+ T cells and assess the association between TLSs and response to nivolumab treatment. A total of 19 patients were analyzed. In patients with partial response (PR) to nivolumab, numerous TLS were observed, and CD103+ T cells were found in and around TLS. Patients with many TLS experienced immune-related adverse events more often than those with few TLS (p = 0.018). The prognosis of patients with TLS high was better than those with TLS low. Patients with a combination of TLS high and CD103 high tended to have a better prognosis than other groups. Our results suggested that TLS status might be a predictor of nivolumab effectiveness. [ABSTRACT FROM AUTHOR]

Patterned cell culturing is one of the most useful techniques for understanding the interaction between geometric conditions surrounding cells and their behaviors. The authors previously proposed a simple method for cell patterning with an agarose gel microstructure fabricated by microcasting with a degassed polydimethylsiloxane (PDMS) mold. Although the vacuum pressure produced from the degassed PDMS can drive a highly viscous agarose solution, the influence of solution viscosity on the casting process is unknown. This study investigated the influences of micro-channel dimensions or solution viscosity on the flow of the solution in a micro-channel of a PDMS mold by both experiments and numerical simulation. It was found experimentally that the degassed PDMS mold was able to drive a solution with a viscosity under 575 mPa·s. A simulation model was developed which can well estimate the flow rate in various dimensions of micro-channels. Cross-linked albumin has low viscosity (1 mPa·s) in aqueous solution and can undergo a one-way dehydration process from solution to solid that produces cellular repellency after dehydration. A microstructure of cross-linked albumin was fabricated on a cell culture dish by the microcasting method. After cells were seeded and cultivated on the cell culture dish with the microstructure for 7 days, the cellular pattern of mouse skeletal myoblast cell line C2C12 was observed. The microcasting with cross-linked albumin solution enables preparation of patterned cell culture systems more quickly in comparison with the previous agarose gel casting, which requires a gelation process before the dehydration process. [ABSTRACT FROM AUTHOR]

Precipitation, as a primary hydrological variable in the water cycle plays an important role in hydrological modeling. The reliability of hydrological modeling is highly related to the quality of precipitation data. Accurate long-term gauged precipitation in the Mekong River Basin, however, is limited. Therefore, the main objective of this study is to assess the performances of various gridded precipitation datasets in rainfall-runoff and flood-inundation modeling of the whole basin. Firstly, the performance of the Rainfall-Runoff-Inundation (RRI) model in this basin was evaluated using the gauged rainfall. The calibration (2000–2003) and validation (2004–2007) results indicated that the RRI model had acceptable performance in the Mekong River Basin. In addition, five gridded precipitation datasets including APHRODITE, GPCC, PERSIANN-CDR, GSMaP (RNL), and TRMM (3B42V7) from 2000 to 2007 were applied as the input to the calibrated model. The results of the simulated river discharge indicated that TRMM, GPCC, and APHRODITE performed better than other datasets. The statistical index of the annual maximum inundated area indicated similar conclusions. Thus, APHRODITE, TRMM, and GPCC precipitation datasets were considered suitable for rainfall-runoff and flood inundation modeling in the Mekong River Basin. This study provides useful guidance for the application of gridded precipitation in hydrological modeling in the Mekong River basin. [ABSTRACT FROM AUTHOR]

We investigated the characteristics of extracellular matrix (ECM) in the soft tissue of two frozen baby woolly mammoths (Mammuthus primigenius) that died and were buried in Siberian permafrost approximately 40,000 years ago. Morphological and biochemical analyses of mammoth lung and liver demonstrated that those soft tissues were preserved at the gross anatomical and histological levels. The ultrastructure of ECM components, namely a fibrillar structure with a collagen-characteristic pattern of cross-striation, was clearly visible with transmission and scanning electron microscopy. Type I and type IV collagens were detected by immunohistochemical observation. Quantitative amino acid analysis of liver and lung tissues of the baby mammoths indicated that collagenous protein is selectively preserved in these tissues as a main protein. Type I and type III collagens were detected as major components by means of liquid chromatography–mass spectrometry analysis after digestion with trypsin. These results indicate that the triple helical collagen molecule, which is resistant to proteinase digestion, has been preserved in the soft tissues of these frozen mammoths for 40,000 years. [ABSTRACT FROM AUTHOR]

Background: Cholinergic neurons utilize choline (Ch) to synthetize acetylcholine (ACh) and contain a high-affinity Ch transporter, Ch acetyltransferase (ChAT), ACh receptors, and acetylcholinesterase (AChE). As the depletion or malfunction of each component of the cholinergic system has been reported in patients with dementia, many studies have sought to evaluate whether treatment candidates affect each of the cholinergic components. The associated changes in the cholinergic components may be reflected by intra- or extra-cellular ACh levels, with an increase in extracellular ACh levels occurring following AChE inhibition. We hypothesized that increases in intracellular ACh levels can be more sensitively detected than those in extracellular ACh levels, thereby capturing subtle effects in the cholinergic components other than AChE. The objective of this study was to test this hypothesis. Methods: We developed an in vitro model to measure both extracellular and intracellular ACh levels using the human cholinergic neuroblastoma cell line, LA-N-2, which have been reported to express Ch transporter, ChAT, muscarinic ACh receptor (mAChR), and AChE. With this model, we evaluated several drug compounds and food constituents reported to improve cholinergic function through various mechanisms. In addition, we conducted western blotting to identify the subtype of mAChR that is expressed on the cell line. Results: Our cell-based assay system was capable of detecting increases in extracellular ACh levels induced by an AChE inhibitor at relatively high doses, as well as increases in intracellular ACh levels following the administration of lower AChE-inhibitor doses and an mAChR agonist. Moreover, increases in intracellular ACh levels were observed even after treatment with food constituents that have different mechanisms of action, such as Ch provision and ChAT activation. In addition, we revealed that LA-N-2 cells expressed mAChR M2. Conclusion: The findings support our hypothesis and indicate that the developed assay model can broadly screen compounds from drugs to food ingredients, with varying strengths and mechanisms of action, to develop treatments for ACh-relevant phenomena, including dementia and aging-related cognitive decline. [ABSTRACT FROM AUTHOR]

Interoceptive accuracy is an index of the ability to perceive an individual's internal bodily state, including heartbeat and respiration. Individual differences in interoceptive accuracy influence emotional recognition through autonomic nervous activity. However, the precise mechanism by which interoceptive accuracy affects autonomic reactivity remains unclear. Here, we investigated how cardiac reactivity induced by a non-affective external rhythm differed among individuals, using a heartbeat counting task. Because individuals with poor interoceptive accuracy cannot distinguish an external rhythm from their cardiac cycles, it has been hypothesized that the interoceptive effect on heart rate works differently in individuals with good interoceptive accuracy and those with poor interoceptive accuracy. Study participants observed a visual or auditory stimulus presented at a rhythm similar to the participants' resting heart rates. The stimulus rhythm was gradually changed from that of their resting heart rate, and we recorded electrocardiographs while participants were exposed to the stimuli. Individuals with good interoceptive accuracy exhibited a deceleration in heart rate when the rhythm of the auditory stimulus changed. In contrast, in the group with poor interoceptive accuracy, the heart rate decreased only when the stimulus became faster. They were unable to distinguish the rhythm of their own heartbeat from that of the external rhythm; therefore, we propose that such individuals recognize the stimuli at the pace of their heart rate. Individuals with good interoceptive accuracy were able to distinguish their heart rates from the external rhythm. A modality difference was not observed in this study, which suggests that both visual and auditory stimuli help mimic heart rate. These results may provide physiological evidence that autonomic reactivity influences the perception of the internal bodily state, and that interoception and the autonomic state interact to some degree. [ABSTRACT FROM AUTHOR]

Previously, we showed silicone nerve conduits containing a vascular bundle and decellularized allogenic basal laminae (DABLs) seeded with bone marrow-derived mesenchymal stem cells (BMSCs) demonstrated successful nerve regeneration. Nerve conduits should be flexible and biodegradable for clinical use. In the current study, we used nerve conduits made of polyglycoric acid (PGA) fiber mesh, which is flexible, biodegradable and capillary-permeable. DABLs were created using chemical surfactants to remove almost all cell debris. In part 1, capillary infiltration capability of the PGA tube was examined. Capillary infiltration into regenerated neural tissue was compared between the PGA tube with blood vessels attached extratubularly (extratubularly vascularized tube) and that containing blood vessels intratubularly (intratubularly vascularized tube). No significant difference was found in capillary formation or nerve regeneration between these two tubes. In part 2, a 20 mm gap created in a rat sciatic nerve model was bridged using the extratubularly vascularized PGA tube containing the DABLs with implantation of isogenic cultured BMSCs (TubeC+ group), that containing the DABLs without implantation of the BMSCs (TubeC- group), and 20 mm-long fresh autologous nerve graft (Auto group). Nerve regeneration in these three groups was assessed electrophysiologically and histomorphometrically. At 24 weeks, there was no significant difference in any electrophysiological parameters between TubeC+ and Auto groups, although all histological parameters in Auto group were significantly greater than those in TubeC+ and TubeC- groups, and TubeC+ group demonstrated significant better nerve regeneration than TubeC- group. The transplanted DABLs showed no signs of immunological rejection and some transplanted BMSCs were differentiated into cells with Schwann cell-like phenotype, which might have promoted nerve regeneration within the conduit. This study indicated that the TubeC+ nerve conduit may become an alternative to nerve autograft. [ABSTRACT FROM AUTHOR]