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Plant cells are surrounded by a cell wall and do not migrate, which makes the regulation of cell division orientation crucial for development. Regulatory mechanisms controlling cell division orientation may have contributed to the evolution of body organization in land plants. The GRAS family of transcription factors was transferred horizontally from soil bacteria to an algal common ancestor of land plants. SHORTROOT ( SHR ) and SCARECROW ( SCR ) genes in this family regulate formative periclinal cell divisions in the roots of flowering plants, but their roles in nonflowering plants and their evolution have not been studied in relation to body organization. Here, we show that SHR cell autonomously inhibits formative periclinal cell divisions indispensable for leaf vein formation in the moss Physcomitrium patens , and SHR expression is positively and negatively regulated by SCR and the GRAS member LATERAL SUPPRESSOR , respectively. While precursor cells of a leaf vein lacking SHR usually follow the geometry rule of dividing along the division plane with the minimum surface area, SHR overrides this rule and forces cells to divide nonpericlinally. Together, these results imply that these bacterially derived GRAS transcription factors were involved in the establishment of the genetic regulatory networks modulating cell division orientation in the common ancestor of land plants and were later adapted to function in flowering plant and moss lineages for their specific body organizations.

Aims/Introduction Type 1 diabetes is associated with poorer bone quality. Quantitative ultrasound provides an estimate of bone mineral density (BMD) and can also be used to evaluate bone quality, which is associated with an increased fracture risk in people with type 1 diabetes. The aim of this study was to evaluate the association between menopausal status and a bone turnover marker with heel BMD using quantitative ultrasound in women with type 1 diabetes and age‐ and body mass index‐matched controls. Materials and Methods A total of 124 individuals recruited in Kyoto and Osaka, Japan – 62 women with type 1 diabetes (mean age 47.2 ± 17.3 years) and 62 age‐, menopausal status‐, sex‐ and body mass index‐matched non‐diabetic control individuals (mean age 47.3 ± 16.3 years) – were enrolled in this study. Heel BMD in the calcaneus was evaluated using ultrasonography (AOS‐100NW, Hitachi‐Aloka Medical, Ltd., Tokyo, Japan). A bone turnover marker was also measured. Results The heel BMD Z‐score was significantly lower in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. Levels of tartrate‐resistant acid phosphatase‐5b, a bone resorption marker, were significantly higher in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. The whole parathyroid hormone level was significantly lower in both pre‐ and postmenopausal women with type 1 diabetes. Conclusions Lower heel BMD, higher tartrate‐resistant acid phosphatase‐5b level and lower parathyroid hormone were observed in premenopausal women with type 1 diabetes. Premenopausal women with type 1 diabetes require osteoporosis precautions for postmenopause.

Background Severe hypoglycemia (SH) remains a central problem in the management of type 1 diabetes (T1D); however, little is known about the protective and risk factors associated with recurrent SH (RSH). This study aimed to identify the protective and risk factors for RSH in adults with T1D. Methods This cross-sectional study enrolled 287 adults with T1D (mean age: 50.3 ± 14.5 years, male: 36.2%, diabetes duration: 17.6 ± 11.2 years, mean HbA1c: 7.7 ± 0.9%) and divided them into non-SH (n = 262), solitary SH (n = 17), and RSH (n = 8) groups. Impaired awareness of hypoglycemia (IAH) assessed using the Gold’s method, diabetic complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem solving abilities, and treatment data were collected. Results The overall SH rate was 16.7/100 person-years. The odds ratios of diabetic peripheral neuropathy and IAH were associated with an increased risk of RSH (odds ratio [OR]: 5.53 ,95% confidence interval [CI]: 1.18–25.98 and OR: 4.82 [95% CI:1.09–21.23], respectively); hypoglycemia problem-solving perception score was associated with a decreased risk of RSH (OR: 0.35 [95% CI: 0.18–0.69]). The rate of rtCGM use decreased as the SH category increased, but no difference was found in the rate of isCGM use. Conclusion We identified the protective factors, such as hypoglycemia problem-solving perception, in addition to the risk factors for RSH in adults with T1D. Trial registration: University hospital Medical Information Network (UMIN) Center: UMIN000039475)、Approval date 13 February 2020

Background Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D. Methods This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected. Results The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13–5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22–0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37–0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups. Conclusions We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia. Trial registration: University hospital Medical Information Network (UMIN) Center: UMIN000039475)、Approval date 13 February 2020

We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range.This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR;70 mg/dL).The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index 5 was significantly reduced (8.6 % vs 23.7 %, P 0.001).The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM.

Light-field three-dimensional (3D) fluorescence microscopes can acquire 3D fluorescence images in a single shot, and followed numerical reconstruction can realize cross-sectional imaging at an arbitrary depth. The typical configuration that uses a lens array and a single image sensor has the trade-off between depth information acquisition and spatial resolution of each cross-sectional image. The spatial resolution of the reconstructed image degrades when depth information increases. In this paper, we use U-net as a deep learning model to improve the quality of reconstructed images. We constructed an optical system that integrates a light-field microscope and an epifluorescence microscope, which acquire the light-field data and high-resolution two-dimensional images, respectively. The high-resolution images from the epifluorescence microscope are used as ground-truth images for the training dataset for deep learning. The experimental results using fluorescent beads with a size of 10 µm and cultured tobacco cells showed significant improvement in the reconstructed images. Furthermore, time-lapse measurements were demonstrated in tobacco cells to observe the cell division process.

Background Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. Case presentation A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. Conclusions We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

Cell division is essential for growth and development and involves events such as spindle assembly, chromosome separation, and cell plate formation. In plants, the tools used to control these events at the desired time are still poor because the genetic approach is ineffective owing to a high redundancy and lethality, as well as harmful side effects. Accordingly, we screened cell division-affecting compounds, with a focus on Arabidopsis thaliana zygotes, which individually develop in maternal ovules; the cell division was reliably traceable without time-lapse observations. We then identified the target events of the identified compounds using tobacco BY-2 cells for live-cell imaging and proteomics. As a result, we isolated two compounds, PD-180970 and PP2. PD-180970 disrupts microtubule (MT) organization and, thus, nuclear separation, presumably by inhibiting MT-associated proteins (MAP70). PP2 affected class II Kinesin-12 localization at the phragmoplast emerging site and impaired cytokinesis. Moreover, neither chemical caused irreversible damage to viability but they were effective in multiple plant species such as cucumber (Cucumis sativus) and moss (Physcomitrium patens). We propose that the combination of chemical screening based on Arabidopsis zygotes and target event specification focusing on tobacco BY-2 cells can be used to effectively identify novel tools and transiently control specific cell division events that are conserved in diverse plant species.

Background: Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, a reduced incidence of hypoglycemia, and improved quality of life (QOL). To date, however, ...

Intermittent-scanning continuous glucose monitoring (isCGM) is widely used in type 1 diabetes (T1D) patients; however, the education required to prevent hypoglycemia by using isCGM is not established. This study examines the combined effect of isCGM device usage and the education to reduce the time in hypoglycemia in comparison to conventional self-monitoring of blood glucose (SMBG).The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study), a randomized, crossover trial, enrolls 104 T1D patients (age, 20-74 years) with T1D. Participants are randomized to use isCGM combined with structured education (Intervention period) or SMBG (Control period) for 84 days, followed by the other for a further 84 days. During the Intervention period, participants have access to the sensor glucose levels and trend arrow of the device. During the Control period, participants conduct SMBG at least three times a day, and retrospective CGM is used to record the blinded sensor glucose levels. The primary endpoint is the decrease of time in hypoglycemia (70 mg/dL) per day (hour/day) during the Intervention period compared with the Control period. The secondary endpoints include other indices of glycemic control, glycoalbumin, accuracy of isCGM, diabetes-related quality of life (QOL), adherence, and cost-effectiveness. The study protocol has received Certified Review Board (CRB) approval from National Hospital Organization Osaka National Hospital (N2018002, Feb 14, 2019). This study is carried out in accordance with the Declaration of Helsinki and the Clinical Trials Act. The findings will be published in peer-reviewed journals.The ISCHIA study will contribute to the standardization of patient education regarding the prevention of hypoglycemia by using isCGM.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty‐one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P

Background: Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited. Materials and Methods: Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants’ characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent. Results: The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P = .016), but not in the nonadherent group (33.3%-33.3%, P > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P Conclusions: Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

In recent years, the success rate of enterprise IT projects has been said to be about 30% to 40%. IT projects tend to change dynamically during the project period, and project managers (PMs) must maintain a high level of motivation among the project members during that period. However PMs currently identify the motivation levels of project members in a vague manner relying on experience and intuition. Therefore, it is difficult for PMs to obtain a clear picture of the motivation levels of the members. It is thus important to create or identify a mechanism by which project managers can understand the motivation levels of members, and in this paper we propose such a mechanism. In the proposed method, the motivation of project members is first classified into two categories. Next, we measure the motivation in a manner suited to the characteristics of each classification category. Then, we propose a method for visualizing the motivation of members. Finally, we verify the effectiveness of the proposed method through an experiment where the proposed method is applied to actual enterprise projects.

Background The role of radical prostatectomy in treating non-metastatic prostate cancer patients with high prostate-specific antigen levels remains unclear. We evaluated the feasibility and oncological outcomes of radical prostatectomy in non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Methods This retrospective study included 31 patients who were diagnosed as very high-risk prostate cancer (clinical stage of any T, N0-1 M0 and PSA levels ≥50 ng/ml) and underwent radical prostatectomy either as a monotherapy or as a component of multimodal therapy (RP group). Surgery-related complications were investigated. Time to castration-resistant prostate cancer, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method. A total of 47 patients with very high-risk prostate cancer who were treated with androgen deprivation therapy without local therapy served as a control group (ADT group). Survivals were compared between RP group and ADT group in exploratory analyses. Results The median pretreatment prostate-specific antigen was 87 ng/ml and 100 ng/ml in the RP and ADT groups, respectively (P = 0.67). Surgical complications of Clavien-Dindo Grade 3 were documented in nine patients (29%). Ten-year castration-resistant prostate cancer-free, cancer-specific and overall survivals were 78%, 81% and 77% in RP group, respectively, and they were significantly better than those of ADT group (54%, P = 0.006; 54%, P = 0.006 and 38%, P < 0.001). Exploratory multivariate analysis identified radical prostatectomy as the only significant factor associated with a better cancer-specific survival (hazard ratio: 0.25, P = 0.006). Conclusions Radical prostatectomy is feasible for non-metastatic prostate cancer patients with prostate-specific antigen levels of 50 ng/ml or higher. Radical prostatectomy is a viable option for select patients with non-metastatic, very high-risk prostate cancer.

MIKC classic (MIKCC)-type MADS-box genes encode transcription factors that function in various developmental processes, including angiosperm floral organ identity. Phylogenetic analyses of the MIKCC-type MADS-box family, including genes from non-flowering plants, suggest that the increased numbers of these genes in flowering plants is related to their functional divergence; however, their precise functions in non-flowering plants and their evolution throughout land plant diversification are unknown. Here, we show that MIKCC-type MADS-box genes in the moss Physcomitrella patens function in two ways to enable fertilization. Analyses of protein localization, deletion mutants and overexpression lines of all six genes indicate that three MIKCC-type MADS-box genes redundantly regulate cell division and growth in the stems for appropriate external water conduction, as well as the formation of sperm with motile flagella. The former function appears to be maintained in the flowering plant lineage, while the latter was lost in accordance with the loss of sperm.

Glycated hemoglobin (HbA1c) is a widely used marker of glycemic control but can be affected by hemolytic anemia. Glycated albumin (GA) is also affected in patients with liver cirrhosis. We herein report the assessment of glycemic control in a 41-year-old man with dehydrated hereditary stomatocytosis and a PIEZO1 gene mutation complicated by diabetes mellitus and liver cirrhosis due to hemochromatosis. The estimated HbA1c calculated from the average glucose level obtained by continuous glucose monitoring or by self-monitoring of blood glucose was useful for evaluating the glycemic control in this patient, as HbA1c and GA were unreliable due to the coexisting conditions.

Aims / Introduction We investigated the safety of the batteries and power units used in insulin pumps in Japan. Materials and Methods A self-administered questionnaire was sent to the 201 members of the Association for Innovative Diabetes Treatment in Japan (ASINDTJ). Results Fifty-six members responded, and among the 1,499 active devices, 66 had episodes of trouble related to the batteries and power units. The ratio of reported troubles to the number of insulin pumps was significantly higher in insulin pumps with CGM sensor compared to insulin pumps without CGM sensor (Odds ratio 2.82, P < 0.05). The cause and the consequences varied. The brands of the batteries varied; alkaline batteries purchased at drug stores and other shops accounted for 19.7%. Termination of battery life within 72 hours of usage was reported most frequently (50.0%), suspension of the insulin pump (21.2%) and leakage of the battery fluid (4.5%) followed. Fifty-three point two percent of the reported insulin pumps needed to be replaced, and 37.1% of them recovered after replacement of the battery. Conclusions As trouble related to the batteries and power units of insulin pumps was frequent, practical guidance should be provided to respective patients regarding the usage of reliable batteries, and to be well prepared for unexpected insulin pump failure. This article is protected by copyright. All rights reserved.