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Aims: Are nurses adapting to the mechanized nursing practice environment? Is it possible for nurses to collaborate with technology to provide care to patients? The aim of the study is to investigate what nurses feel about using technology in nursing practice. Background: Preventing patients from falling is one of the nursing tasks that can be helped by using technology, such as sensors. However, little is known about how nurses experience and feel the use of technological beds for monitoring functionality within clinical nursing practice. Especially it is indicated that alarm fatigue makes nurses and patients fatigued and induces a dissonance between nurses and technology. Objective: To clarify the experiences of nurses in clinical practice following the introduction of a bed with monitoring and fall prevention technology (technology bed). Methods: We interviewed 12 nurses working at a hospital about their nursing practice experiences with the technology bed. Results: The content of the interview was classified into three categories: ‘providing a safe environment’, ‘limitation of entry into machine care scenes’, and ‘nurses’ dilemmas’; with eight themes describing nursing practice: (1) strategies of fall prevention, (2) decrease in nurses’ burden, (3) not good at using technology (all tools must be easy to use), (4) inefficiency such as over-engineering, (5) patients feel annoyed by frequent visits from nurses, (6) limitations of utilization from a nursing perspective, (7) nurse resistance to equipment introduction and (8) ethical issues. Conclusion: Although technology beds could effectively prevent falls, many nurses face an ethical dilemma in using these beds. It would be important for nurses to recognize the role of technology, embrace it, and raise awareness of collaborating with technology to eliminate a dissonance between technology and nurses.

This is a preprint version submitted to review for publication on the IEEE Transactions on Biomedical Engineering (TBME).In this study we investigated the estimation method of cross-bicoherence to infer quadratic phase coupling (QPC) in interaction networks based on empirical Bayes estimation. Nonlinear interaction, ubiquitous in a wide range of biomedical fields, often makes it challenging to apply conventional parametric approaches. While cross-bicoherence has been recognized as a key statistic of QPC, prior studies have not elucidated how reliable the estimation can be for realistic time series. This work demonstrates that cross-bicoherence estimated by the proposed method effectively detects QPC, with illustrative simulation studies of both typical QPC and neural mass models of cortical columns.

Aiming to diversify photocatalytic systems for CO2 reduction using metal complexes, this study investigated the use of various ionic liquids as reaction solvents. The photophysical properties of an Ir(III) complex, functioning as a photosensitiser, and the photocatalytic ability of mixed systems consisting of the Ir(III) photosensitiser and a Re(I) catalyst in twelve kinds of ionic liquids were systematically investigated by comparison with those in N,N-dimethylacetamide (DMA), which is a standard solvent for photocatalytic CO2 reduction. Even though the photophysical properties of the Ir(III) complex in ionic-liquid solutions were quite similar to those in DMA, both the photosensitising ability of the Ir complex and the photocatalytic abilities of the systems strongly depended on the structures of the ionic liquids. Several ionic liquids were successfully used as new solvents for the photocatalytic systems showing durability similar to or higher than DMA solutions. The results demonstrated that even a small modification of the molecular structures of ionic liquids can control the efficiencies of both the photosensitising cycles and the catalytic cycles for CO2 reduction.

This study investigates the equivalence or compatibility between U-Net and visual segmentations of fibroglandular tissue regions by mammography experts for calculating the breast density and mean glandular dose (MGD). A total of 703 mediolateral oblique-view mammograms were used for segmentation. Two region types were set as the ground truth (determined visually): (1) one type included only the region where fibroglandular tissue was identifiable (called the ‘dense region’); (2) the other type included the region where the fibroglandular tissue may have existed in the past, provided that apparent adipose-only parts, such as the retromammary space, are excluded (the ‘diffuse region’). U-Net was trained to segment the fibroglandular tissue region with an adaptive moment estimation optimiser, five-fold cross-validated with 400 training and 100 validation mammograms, and tested with 203 mammograms. The breast density and MGD were calculated using the van Engeland and Dance formulas, respectively, and compared between U-Net and the ground truth with the Dice similarity coefficient and Bland–Altman analysis. Dice similarity coefficients between U-Net and the ground truth were 0.895 and 0.939 for the dense and diffuse regions, respectively. In the Bland–Altman analysis, no proportional or fixed errors were discovered in either the dense or diffuse region for breast density, whereas a slight proportional error was discovered in both regions for the MGD (the slopes of the regression lines were −0.0299 and −0.0443 for the dense and diffuse regions, respectively). Consequently, the U-Net and ground truth were deemed equivalent (interchangeable) for breast density and compatible (interchangeable following four simple arithmetic operations) for MGD. U-Net-based segmentation of the fibroglandular tissue region was satisfactory for both regions, providing reliable segmentation for breast density and MGD calculations. U-Net will be useful in developing a reliable individualised screening-mammography programme, instead of relying on the visual judgement of mammography experts.

Retinitis pigmentosa (RP) and macular dystrophy (MD) are characterized by gradual photoreceptor death in the retina and are often associated with genetic mutations, including those in the prominin-1 (Prom1) gene. Prom1-knockout (KO) mice recapitulate key features of these diseases including light-dependent retinal degeneration and constriction of retinal blood vessels. The mechanisms underlying such degeneration have remained unclear, however. We here analysed early events associated with retinal degeneration in Prom1-KO mice. We found that photoreceptor cell death and glial cell activation occur between 2 and 3 weeks after birth. Whereas gene expression was not affected at 2 weeks, the expression of several genes was altered at 3 weeks in the Prom1-KO retina, with the expression of that for endothelin-2 (Edn2) being markedly upregulated. Expression of Edn2 was also induced by light stimulation in Prom1-KO mice reared in the dark. Treatment with endothelin receptor antagonists attenuated photoreceptor cell death, gliosis and retinal vessel stenosis in Prom1-KO mice. Our findings thus reveal early manifestations of retinal degeneration in a model of RP/MD and suggest potential therapeutic agents for these diseases. This article has an associated First Person interview with the first author of the paper., Summary: The early manifestations of an inherited retinal disease was investigated by means of a transcriptome analysis, and a possible drug-based therapeutic approach (endothelin receptor antagonists) is suggested.

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.

An organism stems from assemblies of a variety of cells and proteins. This complex system serves as a unit, and it exhibits highly sophisticated functions in response to exogenous stimuli that change over time. The complete sequencing of the entire human genome has allowed researchers to address the enigmas of life and disease at the gene- or molecular-based level. The consequence of such studies is the rapid accumulation of a multitude of data at multiple levels, ranging from molecules to the whole body, that has necessitated the development of entirely new concepts, tools, and methodologies to analyze and integrate these data. This necessity has given birth to systems biology, an advanced theoretical and practical research framework that has totally changed the directions of not only basic life science but also medicine. During the symposium of the 95th Annual Meeting of The Physiological Society of Japan 2018, five researchers reported on their respective studies on systems biology. The topics included reactions of drugs, ion-transport architecture in an epithelial system, multi-omics in renal disease, cardiac electrophysiological systems, and a software platform for computer simulation. In this review article these authors have summarized recent achievements in the field and discuss next-generation studies on health and disease. Electronic supplementary material The online version of this article (10.1007/s12576-019-00667-8) contains supplementary material, which is available to authorized users.

In individualized screening mammography, a breast density is important to predict potential risks of breast cancer incidence and missing lesions in mammographic diagnosis. Segmentation of the mammary gland region is required when focusing on missing lesions. A deep-learning method was recently developed to segment the mammary gland region. A large amount of ground truth (prepared by mammary experts) is required for highly accurate deep-learning practice; however, this work is time- and labor-intensive. To streamline the ground truth in deep learning, we investigated a difference in acquired mammary gland regions among multiple radiological technologists having various experience and reading levels, who shared the criteria on segmentation. If we can ignore a skill level for image reading, we can increase a number of training images. Three certified radiological technologists segmented the mammary gland region in 195 mammograms. The degree of coincidence among them was assessed with respect to seven factors which indicated the feature of segmented regions including the breast density and mean glandular dose, using Student’s t-test and Bland-Altman analysis. The assessments made by the three radiological technologists were consistent considering all factors, except the mean pixel value. Thus, we concluded that the ground truths prepared by multiple practitioners with different experiences can be accepted for the segmentation of the mammary gland region and they are applicable for training images if they stringently share the criteria on the segmentation.

Bronchopleural fistula is one of the most serious postoperative complications caused by the incomplete healing of a bronchial stump. Fibroblasts play an important role in wound healing by facilitating connective tissue formation and inducing angiogenesis. We developed a method for production of multilayered fibroblast sheets that secreted some growth factors and promoted wound healing. The present study aimed to assess the treatment effect of multilayered fibroblast sheets on bronchial stump healing. In this rat model, left pneumonectomy was performed, and multilayered fibroblast sheets derived from autologous oral mucosal tissues were transplanted to the bronchial stump. The changes in the bronchial stump were examined macroscopically, histologically, and mechanically. The fibroblast sheets promoted the formation of thick connective tissues around the bronchial stump. The formed connective tissues were accompanied by new blood vessels, and fibrosis was observed over time. Then, 7 days after the transplantation of the fibroblast sheets, the bronchial wall became significantly thicker, and the area of the blood vessels for the bronchial wall tissues was significantly larger in the experimental group than in the control group. In addition, the burst pressure in the bronchial stump was significantly higher in the experimental group than in the control group. Bronchial stumps were reinforced by the transplantation of multilayered fibroblast sheets derived from autologous oral mucosal tissues.

Functional connectivity between cerebral cortical regions during natural sleep has attracted a keen interest from both cognitive and clinical neuroscientists because of its importance in understanding the default mode network of human brain. Multiple recordings of functional near-infrared spectroscopy (fNIRS) in several sleep phases make it possible for us to detect potential differences of directional interactions between cortical areas from healthy subjects and patients with ADHD or sleep disorders. Namely we propose a computational method to estimate time-domain Granger causality among fNIRS time series using a Kolmogorov–Smirnov test based on F-statistics. In order to validate indication of directional interactions, we also apply convergent cross-mapping to the time series as an alternative approach to causality based on state space reconstruction of dynamical systems. Comparing the averaged heatmaps of significant causal pairs of regions, we show that the map of directional interactions varies for each sleep phase, e.g., REM, of the same subject. The observation suggests an unexplored source for non-invasive classification benchmark of the above cognitive disorders.

ObjectiveDespite the high risk of missing lesions in mammography, the missed lesion rate is yet to be clinically established. Further, no breast phantoms with adjustable breast density currently exist. We developed a novel, adjustable-density breast phantom with a composition identical to that of actual breasts, and determined the quantitative relationship between breast density and the missed lesion rate in mammography.MethodsAn original breast phantom consisting of adipose- and fibroglandular-equivalent materials was developed, and a receiver operating characteristic (ROC) study was performed. Breast density, which is the fraction by weight of fibroglandular to total tissue, was adjusted to 25%, 50%, and 75% by arbitrarily mixing the two materials. Microcalcification, mass lesions, and spiculated lesions, each with unique characteristics, were inserted into the phantom. For the above-mentioned fibroglandular densities, 50 positive and 50 negative images for each lesion type were used as case samples for the ROC study. Five certified radiological technologists participated in lesion detection.ResultsThe mass-lesion detection rate, according to the area under the curve, decreased by 18.0% (p= 0.0001, 95% Confidence intervals [CI] = 0.1258 to 0.1822) and 37.8% (p= 0.0003, 95% CI = 0.2453 to 0.4031) for breast densities of 50% and 75%, respectively, compared to that for a 25% breast density. A similar tendency was observed with microcalcification; however, spiculated lesions did not follow this tendency.ConclusionsWe quantified the missed lesion rate in different densities of breast tissue using a novel breast phantom, which is imperative for advancing individualized screening mammography.

Patients affected by attention-deficit/hyperactivity disorder (ADHD) are characterized by impaired executive functioning and/or attentional deficits. Our study is aimed to determine whether the outcomes measured by the attentional network task (ANT), i.e., the reaction times (RT) to specific target and cueing conditions and alerting, orienting, and conflict effects, are affected by cognitive training with a dual N-Back task. We considered three groups of young adult participants: ADHD patients without medication, ADHD with medication (MADHD), and age/education-matched controls (CTL). Working memory training began the day after the pretest. Participants were asked to perform 20 trainings composed of 20 blocks during an entire month. They were told that they would have to practice the dual N-Back task for about 30 min per day during the week and to rest for two days in the weekend. Each experimental group was randomly assigned into two conditions, the first with a progressive level (PL) of difficulty training, while the second was blocked at the level 1 during the whole training phase (baseline training). We observed that PL training was beneficial with reduced RTs in all groups and reduced conflict effects. MADHD showed a positive effect already with baseline training, whereas ADHD showed no significant reduction of neither RTs nor conflict effect after baseline training. No group showed any effect of training on alerting and orienting effects.

Purpose To identify the upstream regulators (URs) involved in the onset and pathogenesis of ovarian endometrioma. Methods Recently, a method called Significance-based Modules Integrating the Transcriptome and Epigenome (SMITE) that uses transcriptome data in combination with publicly available data for identifying URs of cellular processes has been developed. Here, we used SMITE with transcriptome data from ovarian endometrioma stromal cells (ovESCs) and eutopic endometrium stromal cells (euESCs) in combination with publicly available gene regulatory network data. To confirm the URs identified by SMITE, we developed a Boolean network simulation to see if correcting aberrant expressions of the identified genes could restore the entire gene expression profile of ovESCs to a profile similar to that of euESCs. We then established euESCs overexpressing the identified gene and characterized them by cell function assays and transcriptome analysis. Results SMITE identified 12 potential URs in ovarian endometrioma that were confirmed by the Boolean simulation. One of the URs, HOXC8, was confirmed to be overexpressed in ovESCs. HOXC8 overexpression significantly enhanced cell proliferation, migration, adhesion, and fibrotic activities, and altered expression statuses of the genes involved in transforming growth factor (TGF)-β signaling. HOXC8 overexpression also increased the expression levels of phosphorylated SMAD2/SMAD3. The increased adhesion and fibrosis activities by HOXC8 were significantly inhibited by E-616452, a selective inhibitor of TGF-β receptor type I kinases. Main conclusions Integrated genomic approaches identified HOXC8 as an UR in ovarian endometrioma. The pathological features of ovarian endometrioma including cell proliferation, adhesion, and fibrosis were induced by HOXC8 and its subsequent activation of TGF-β signaling.

This study is aimed to automatically segment mammary gland region into scattered mammary glands and fatty breasts using deep learning method. Total 433 mediolateral oblique-view mammograms of Japanese women were collected and confirmed for scattered mammary glands or fatty breasts; using BI-RADS’s classification. First, manually contoured mammary gland regions were determined for all mammograms as ground truths by three certified radiological technologists. Second, the U-net model was employed to segment the mammary gland region automatically. This model is a type of convolutional neural network (CNN) mainly aimed at medical image segmentation. The segmentation accuracies were assessed based on five criteria, Dice coefficients, breast densities, mean gray values, centroids, and sizes of mammary gland region. The Dice coefficient was 0.915. The mean size of mammary gland regions obtained by the Unet was 8.7% larger than that of the ground truths. The mean centroid coordinates of mammary gland regions by the U-net were shifted 1.6 and 5.4 mm on average in mediolateral and craniocaudal directions, respectively from ground truths. The mean gray value of mammary gland regions obtained by the U-net was only 0.4% higher compared with ground truths. The resultant difference was 0.4% on average in breast densities between ground truths and the segmented mammary gland regions. We found significant similarity in the ground truths and the data generated by deep learning on all the parameters, thereby attesting the efficacy of this method for segmenting the mammary gland regions of not only the dense breasts but also the scattered mammary gland- and fatty- breasts.

Receiver operating characteristic (ROC) examination was performed to investigate the effectiveness of high-luminance monitors in digital X-ray mammography. For this purpose, an original breast phantom consisting of adipose and fibroglandular equivalent tissues with an identical X-ray absorption characteristic over the entire mammographic photon energy range was developed. Furthermore, the phantom’s fibroglandular density and distribution could be changed arbitrarily. Three types of lesions, microcalcification, mass, and spiculated, were inserted into the breast phantom, and the ROC examination was performed by five radiological technologists certified in screening mammography, to obtain the area under the curve. A liquid crystal display (LCD) monitor with 5 megapixels in a 21-inch display size calibrated to a grayscale standard display function curve was used for the observation. The monitor was set to 600, 900, and 1200 cd/m2 in maximum luminance. The experimental details were fibroglandular density of 25%, respective 50 positive and negative images, and free observation time and distance. As a result, the dependence on monitor luminance differed according to the lesion type. The detectability of microcalcification increased with the increase in the luminance of the monitor. Spiculated lesions were similar for all luminance changes. The detectability of mass lesions was significantly higher at 900 cd/m2 than at 600 cd/m2 . There was no significant difference between those at 900 cd/m2 and 1200 cd/m2 . In conclusion, the maximum luminance of the diagnostic LCD monitor for mammography should be at least 900 cd/m2 to guarantee stable detectability.

Aiming to diversify photocatalytic systems for CO2 reduction using metal complexes, this study investigated the use of various ionic liquids as reaction solvents. The photophysical properties of an Ir(iii) complex, functioning as a photosensitiser, and the photocatalytic ability of mixed systems consisting of the Ir(iii) photosensitiser and a Re(i) catalyst in twelve kinds of ionic liquids were systematically investigated by comparison with those in N,N-dimethylacetamide (DMA), which is a standard solvent for photocatalytic CO2 reduction. Even though the photophysical properties of the Ir(iii) complex in ionic-liquid solutions were quite similar to those in DMA, both the photosensitising ability of the Ir complex and the photocatalytic abilities of the systems strongly depended on the structures of the ionic liquids. Several ionic liquids were successfully used as new solvents for the photocatalytic systems showing durability similar to or higher than DMA solutions. The results demonstrated that even a small modification of the molecular structures of ionic liquids can control the efficiencies of both the photosensitising cycles and the catalytic cycles for CO2 reduction.

Polycrystalline diamond (PCD) tools are widely used for cutting tools because PCD has no crystal orientation and is an isotropic material, it is low in cost, and it is easily machined by electric discharge machining. PCD is sintered from diamond abrasives with an alloy metal, such as cobalt, and it is difficult to reduce the surface roughness and the edge accuracy compared with single crystal diamond. In this study, high efficiency and high precision machining of the PCD wheel were investigated. In the experiments, PCD wheels were ground with a diamond wheel, and the effects of the grinding direction and the load on the tool preciseness and the scribing performance were examined.