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For acute cholecystitis with high surgical risk, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has shown high clinical and technical success rates. Dilation of the punctured fistula is a technically challenging aspect of EUS-GBD. Over-dilation makes stent insertion easier; however, it increases the risk of bile leakage. Currently, the endoscopic devices available for EUS-GBD are limited, which presents device-related shortcomings. When the stent cannot pass through the dilated fistula, the deployment of a conventional double-pigtail plastic stent requires discarding of the stent and re-puncturing of the gallbladder. Recently, a novel integral double-pigtail plastic stent tied with a pusher catheter that allows the stent to be pulled back on insertion failure was developed. Here, we describe a patient in whom EUS-GBD was successfully performed using this novel stent that enables adjustment during dilation, making EUS-GBD safer.

著者人数: 13名, Accepted: 2018-11-28, 資料番号: SA1180242000

In electrocardiographic (ECG)-gated computed tomography (CT) for diagnosis of cardiac diseases, radiation dose and image quality are optimized by limiting field of view (FOV) and centering on the heart. However, it is necessary to set wide FOV with large bowtie filter depending on patient positioning or various diagnoses such as aortic diseases. The purpose of this study is to clarify influence of bowtie filter and patient positioning on in-plane dose distribution, organ-absorbed dose, image quality in ECG-gated CT. In-plane dose distribution and organ-absorbed dose were evaluated with radio photoluminescence glass dosimeters, and signal-to-noise ratio (SNR) were measured for evaluation of image quality. The bowtie filter was used small (S) and large (L). With automatic exposure control, volume computed tomography dose index was 55.3 mGy at S and 71.8 mGy at L. The phantom was positioned on the heart of phantom (Heart) and the center of phantom (Body). In Heart-L compared with Heart-S, organ-absorbed dose was 1.29 times at breasts. In Heart-S compared with Body-S, in-plane dose distribution was increased 25% at left anterior and decreased 20% at right posterior. In SNR, S and L were decreased from 50 mm off-center. To set appropriate bowtie filter and positioning was reduced radiation dose and improved image quality in ECG-gated CT.

Although writing activities present a good opportunity to develop metacognitive skills, it is difficult for novice learners to be aware of logical inconsistencies or a lack of perspective, even in their own documents. To promote such learners’ metacognitive activities, a novel eye-movement visualization system is proposed that activates learners’ metacognitive inference activities by expanding a previously proposed framework. The system intuitively visualizes all reading processes of the expert, who critically reads the learner’s document, as a timeline graph. In addition, it has several support functions that provide information on the expert’s characteristic reading behaviors and the logical structure of documents. The initial experiment showed that the proposed graph visualization system has the potential to activate learners’ metacognitive inference activities, even after verifying the previously proposed eye-movement visualization tools. It was also confirmed that learners can generate the correction points by themselves, even in documents that they had already checked critically before submission.

When holding creative discussions with other people, it is important not only that the speaker accurately understand what he/she wants to convey but also that the speaker express knowledge in a way that is understandable to the listener. “Reflective thinking” (knowledge restructuring) in which one considers what one wants to say and “verbalization of reasoning” driven by thinking that is conscious of other people are mutually interactive and deepen understanding of what one is trying to say. This study focuses on academic research meetings as a forum conducive to creative discussions and on the preparation of research materials (research documentation) as the product of the verbalization of reasoning that takes knowledge transmission into account. It proposes, in particular, a self-conversation support system that supports the iteration of these two activities.

In the Large Helical Device, the divertor detachment has been attempted by application of resonant magnetic perturbation (RMP) field and Ne gas puffing in electron cyclotron resonance- heated discharges for compatibility of high central electron temperature and low divertor heat load. Two kinds of divertor detachment phases were observed. The first one appeared transiently just after the Ne gas puffing (1st detachment), and the second one appeared steadily in the latter half of the discharge (2nd detachment). Space-resolved extreme ultraviolet spectroscopy revealed that NeVI-NeVIII emissions increased slightly outside the last closed flux surface (LCFS), while NeIX and NeX emissions increased inside the LCFS in the 1st detachment phase. Although in the 1st detachment the divertor heat load was significantly reduced, the central electron temperature also decreased because the Ne ions were penetrated inside the LCFS as a radiation source. In the 2nd detachment phase, NeVI-NeVIII emissions increased outside the LCFS while NeIX and NeX emissions kept low intensity inside the LCFS. In this phase, low divertor heat load and high central electron temperature were obtained simultaneously because the Ne ions were localized outside the LCFS as a radiation source. The profile measurements of Ne emission show that the edge island structure created by the RMP application impacts on the impurity emission distribution, where the peak of the emission shifts radially stepwise as the detachment proceeds.

The ability for metacognitive thought, or “thinking about thinking,” is recognized as an increasingly important skill for the future enrichment of social life. However, this skill is difficult to teach because it involves implicit cognitive activities that cannot be perceived by an outside observer. In this study, we propose an interpretation framework of metacognition as one approach to considering metacognitive thinking processes. This framework serves as the design principles for developing a system that makes it possible to provide metacognitive interpretations of gaze behaviors and thought operation actions and provides a common basis for sharing and comparing knowledge from analysis results. In this study, for an example of framework-based system development, we construct a thinking externalization application and thinking analysis support system with a thinking task of dissolving belief conflict as the theme. We also demonstrate an example of the analysis of thinking about belief conflict, as derived from lower-level and higher-level thinking interpretation rules. From the example results of the defined interpretation rules, we found that the desired behavior occurred, demonstrating the postulated possibility of capturing the thought process. By realizing a series of phases on the framework proposed in this paper, it contributes to the feasibility of grasping the metacognition process and accumulating knowledge about it.

A solid solution of GaN and ZnO (GaN:ZnO) is promising as a photocatalyst for visible light-driven overall water splitting to produce H2. However, several obstacles still exist in the conventional preparation procedure of GaN:ZnO. For example, the atomic distributions of Zn and Ga are non-uniform in GaN:ZnO when a mixture of the metal oxides, i.e., Ga2O3 and ZnO, is used as a precursor. In addition, GaN:ZnO is generally prepared under harmful NH3 flow for long durations at high temperatures. Here, a facile synthesis of GaN:ZnO with homogeneous atomic composition via a simple and safe procedure is reported. A layered double hydroxide (LDH) containing Zn2+ and Ga3+ was used to increase the uniformity of the atomic distributions of Zn and Ga in GaN:ZnO. We employed urea as a nitriding agent instead of gaseous NH3 to increase the safety of the reaction. Through the optimization of reaction conditions such as heattreatment temperature and content of urea, single-phase GaN:ZnO was successfully obtained. In addition, the nitridation mechanism using urea was investigated in detail. NH3 released from the thermal decomposition of urea did not directly nitride the LDH precursor. X-ray absorption and infrared spectroscopies revealed that Zn(CN2)-like intermediate species were generated at the middle temperature range and Ga–N bonds formed at high temperature along with dissociation of CO and CO2., This file includes Supporting Information., This work was supported by JSPS KAKENHI Grant Number JP16H06438, JP16H06441, JP17H05483, JP17H03392. This work was partly supported by the Center for Functional Nano Oxide at Hiroshima University. The synchrotron radiation experiments were performed at the BL01B1 beamline of SPring-8 with the approval of the Japan Synchrotron Radiation Research 32 Institute (JASRI) (Proposal No. 2017B1043 and 2018A1749).

Topological defects in liquid crystals (LCs) dominate molecular alignment/motion in many cases. Here, the neural network (NN) function has been introduced to predict the LC orientation condition (orientation angle and order parameter) at local positions around topological defects from the phase/polarization microscopic color images. The NN function was trained in advance by using the color information of an LC in a planar alignment cell for different orientation angles and temperatures. The photo-induced changes of LC molecules around topological defects observed by the time-resolved measurement was converted into the image sequences of the orientation angle and the order parameter change. We found that each pair of brushes with different colors around topological defects showed different orientation angle and ordering changes. The photo-induced change was triggered by the photoisomerization reaction of molecules, and one pair of brushes increased in its order parameter just after light irradiation, causing gradual rotation in the brush. The molecules in the other pair of brushes were disordered and rotated by the effect of the initially affected region. This combination approach of the time-resolved phase/polarization microscopy and the NN function can provide detailed information on the molecular alignment dynamics around the topological defects.

Nitrogen (N) and carbon (C) are essential elements for plant growth and crop yield. Thus, improved N and C utilisation contributes to agricultural productivity and reduces the need for fertilisation. In the present study, we find that overexpression of a single rice gene, Oryza sativa plasma membrane (PM) H+-ATPase 1 (OSA1), facilitates ammonium absorption and assimilation in roots and enhanced light-induced stomatal opening with higher photosynthesis rate in leaves. As a result, OSA1 overexpression in rice plants causes a 33% increase in grain yield and a 46% increase in N use efficiency overall. As PM H+-ATPase is highly conserved in plants, these findings indicate that the manipulation of PM H+-ATPase could cooperatively improve N and C utilisation, potentially providing a vital tool for food security and sustainable agriculture., Improved utilisation of nitrogen and carbon could boost agricultural productivity. Here Zhang et al. show that overexpression of a single gene, encoding the plasma membrane H+ -ATPase 1 OSA1, is able to increase both carbon fixation via photosynthesis and nitrogen assimilation via ammonium uptake in rice.

Although primarily a respiratory illness, several studies have shown that COVID-19 causes elevation of liver enzymes and various gastrointestinal (GI) symptoms. The aim of this study was to undertake a systematic review and meta-analysis to determine whether the presence of gastrointestinal (GI) symptoms contributed toward COVID-19 severity, and identify the GI symptoms characteristic of severe COVID-19. We conducted a literature search of PubMed from December 1, 2019, to June 30, 2020, and identified all reports with GI symptoms reported. A meta-analysis comparing the severity of COVID-19 with the presence of liver enzyme elevation and GI symptoms was performed using RevMan version 5.4. Pooled data from 15,305 unique reverse transcriptase–polymerase chain reaction positive COVID-19 patients from 44 studies were analyzed. We found that the severe COVID-19 patients significantly had abdominal pain compared to the non-severe COVID-19 patients (OR = 2.70, 95% CI 1.17–6.27, Z = 2.32, p = 0.02, I2 = 0%) by analyzed 609 patients of 4 studies who reported both abdominal pain and COVID-19 severity. However, there was no significant difference in the incidence of diarrhea, nausea, or vomiting between the two groups. Thus, this systematic review and meta-analysis demonstrated that abdominal pain could be characteristic of severe COVID-19 infections. Compared with other viral infections that primarily infect the respiratory system, patients with COVID-19 have a slightly lower frequency of diarrheal symptoms with abdominal pain. However, to confirm this, further studies with COVID-19 patients across various countries and ethnicities are required. Supplementary Information The online version contains supplementary material available at 10.1007/s00535-021-01778-z.

According to previous studies, R-(-)-venlafaxine (VEN) has higher enantioselectivity than S-(+)-VEN, and the plasma concentration of R-(-)-VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects of CYP2D6*10 genotypes on the steady-state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O-desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (PCR) was used to determine the CYP2D6*10 genotypes. The plasma concentrations of S-(+)-VEN were approximately 1.9-fold higher than those of R-(-)-VEN. The plasma concentrations of S-(+)-VEN and R-(-)-VEN seemed to be higher in individuals with two mutant alleles of CYP2D6*10, although no significant differences were found in the plasma levels of S-(+)-VEN and R-(-)-VEN between CYP2D6*10 genotypes. The number of mutant alleles of CYP2D6*10 was a significant factor associated with the R-(-)-ODV/R-(-)-VEN ratio (P = .004) in multiple regression analysis. This suggests that CYP2D6*10 mutations affect the metabolism of R-(-)-VEN and S-(+)-VEN. Further studies are needed to examine how these findings affect clinical practice.

Objectives The present study aimed to examine the effectiveness of proton magnetic resonance spectroscopy (1HMRS) in determining the progression of neurological symptoms resulting in acute ischemic stroke in patients with lenticulostriate artery (LSA) infarction. Materials and Methods 1HMRS was performed within 72 h after neurological symptom onset. Voxel of interest was placed in tissue that included the pyramidal tract and identified diffusion weighted echo planar spin-echo sequence (DWI) coronal images. Infarct volume in DWI was calculated using the ABC/2 method. 1HMRS data (tNAA, tCr, Glx, tCho, and Ins) were analyzed using LCModel. Progressive neurological symptoms were defined as an increase of 1 or more in the NIHSS score. Patients who underwent 1HMRS after progressive neurological symptoms were excluded. Results In total, 77 patients were enrolled. Of these, 19 patients had progressive neurological symptoms. The patients with progressive neurological symptoms were significantly more likely to be female and had higher tCho/tCr values, higher rates of axial slices ≥ 3 slices on DWI, higher infarct volume on DWI, higher maximum diameter of infarction of axial slice on DWI, and higher SBP on admission compared to those without. Multivariable logistic analysis revealed that higher tCho/tCr values were independently associated with progressive neurological symptoms after adjusting for age, sex, and initial DWI infarct volume (tCho/tCr per 0.01 increase, OR 1.26, 95% CI 1.03–1.52, P = 0.022). Conclusions Increased tCho/tCr score were associated with progressive neurological symptoms in patients with LSA ischemic stroke. Quantitative evaluation of 1HMRS parameters may be useful for predicting the progression of neurological symptoms.

Strains of Streptococcus mutans expressing the cell surface collagen-binding protein, Cnm, encoded by cnm (cnm-positive S. mutans), are associated with hypertensive intracerebral hemorrhage (ICH) and the occurrence of cerebral microbleeds (CMBs). Small diffusion-weighted imaging (DWI) hyperintensities in patients with acute ICH are also associated with CMBs. However, the association between cnm-positive S. mutans and DWI hyperintensities is unclear. Hence, this study aimed to investigate the association between cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.Patients with acute ICH were prospectively registered at three hospitals. Dental plaque specimens were collected within 4 days after admission, and cnm-positive S. mutans was detected using the polymerase chain reaction. Magnetic resonance imaging at 14 ± 5 days after admission was used to evaluate DWI hyperintensities and CMBs.A total of 197 patients were enrolled in this study. cnm-positive S. mutans was detected in 30 patients (15.2%), and DWI hyperintensities were observed in 56 patients (28.4%). Patients with cnm-positive S. mutans had a higher frequency of DWI hyperintensities (50.0% vs 24.6%; p = 0.008) and a higher number of CMBs (5.5 vs 1.5; p 0.001) than those without cnm-positive S. mutans. Multivariable logistic analysis revealed that the presence of cnm-positive S. mutans was independently associated with DWI hyperintensities (OR 2.38; 95% CI 1.01-5.61; p = 0.047) after adjusting for several confounding factors.This study found an association between the presence of cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.

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This work-in-progress paper describes a project to support co-education of teams such as a manufacturing department. Often, these teams do not update manuals. Data such as implementation records and incident reports are often stored separately and are difficult to retrieve. Consequently, business improvement and creation of new methods might not proceed. In this paper, we propose a method to help the team members to gather and knit their data and knowledge together. It helps both team experts and novices to acquire the necessary knowledge and skills. Examples are presented of how these data and knowledge are constructed and used.

Background Cerebral amyloid angiopathy (CAA) is a sporadic condition in the elderly and is associated with Alzheimer’s disease. The younger cases, however, may have a history of traumatic brain injury (TBI) during infancy. Case Presentation We present a case of a 37-year-old man who had cerebral lobar hemorrhage. Magnetic resonance imaging revealed several lobar microbleeds, which along with the asymptomatic, lobar hemorrhages increased every year. At the age of 40 years, he developed mild cognitive impairment. Cerebrospinal fluid (CSF) analysis revealed a markedly decreased level of amyloid β42. Moreover, he had a subdural hematoma during infancy. Thus, we diagnosed him with CAA, which was related to the TBI at infancy. Conclusion TBI at infancy can be a remote cause of middle-aged CAA and dementia. This was supported by the low Aβ42 level in the CSF analysis.

The proposed high-dorsiflexion assistive robotic technology (RT) is aimed to assist ankle movement during gait rehabilitation. A McKibben-type artificial muscle facilitates dorsiflexion in the swing phase by lifting a forefoot of a stroke patient’s paralyzed side. In spite of the great potential of improving dorsiflexion owing to the proposed RT observed in the previous clinical results, the current approach is applicable only to the passive ankle gait rehabilitation with full assistance. It is believed that ensuring patients’ voluntary effort in rehabilitation is the key for long-term recovery. In the present research, we conducted an experiment to evaluate our RT’s effects on six healthy participants, and analyzed whether their voluntary ankle movements were affected due to the current assistance strategy. Compared with normal walk, significant decrease in processed surface electromyography signal (p = 8.62×10-3), significant early timing of a push-off motion (p =2.60×10-4), and significant smaller push-off angle (p = 1.50×10-4) were observed compared with intervention of the proposed RT. On the other hand, a significant trend of decrease in the ankle dorsiflexion rate in the swing phase is observed during intervention (p = 0.06949). Based on the obtained results, we concluded that unlike the contraction speed of an artificial muscle that did not show any considerable impact, the excessively early activation of the RT assistance affected voluntary ankle movement.

BACKGROUND Venlafaxine (VEN) is primarily metabolized by CYP2D6. Although several studies have reported the significant effects of CYP2D6 on VEN and O-desmethylvenlafaxine (ODV) pharmacokinetics in Whites, limited data are available regarding the effects of the Asian-specific CYP2D6 genotype on VEN metabolism. This study evaluated the effects of the CYP2D6*10 and CYP2D6*5 genotypes on the steady-state plasma concentrations of VEN and ODV in Japanese patients. METHODS This study included 75 Japanese patients with depression who were treated with VEN. Steady-state plasma concentrations of VEN and ODV were measured using liquid chromatography. Polymerase chain reaction was used to determine CYP2D6 genotypes. A stepwise multiple regression analysis was performed to analyze the relationship between independent variables (sex, age, smoking habit, and number of mutated alleles, CYP2D6*10 and CYP2D6*5), subject-dependent variables (plasma concentrations of VEN and ODV [all corrected for dose and body weight]), and the ODV/VEN ratio. RESULTS Significant correlations were observed between the daily dose of VEN (corrected for body weight) and plasma concentrations of VEN (r = 0.498, P < 0.001) and ODV (r = 0.380, P = 0.001); ODV plasma concentrations were approximately 3.2 times higher than VEN plasma concentrations (VEN versus ODV = 18.60 ng/mL versus 59.10 ng/mL). VEN plasma concentrations (corrected for dose and body weight) did not differ with differing numbers of CYP2D6-mutated alleles. However, the ODV/VEN ratio decreased as the number of mutated CYP2D6 alleles increased (P = 0.001). CONCLUSIONS This is the first study to examine the effects of CYP2D6*10 in a clinical setting. Although no effects on the plasma concentrations of VEN or ODV were observed, CYP2D6 polymorphism affects the ODV/VEN ratio. Further studies are needed to confirm the clinical relevance of these findings.

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".

How the super-rotation of the Venusian atmosphere is maintained is an outstanding question of the Venus science and geophysical fluid dynamics. We tackled it by using data from Akatsuki. Prior to that, we revisited the meridional circulation by using past observational data: downward solar flux from entry probe and satellite-based radiation observation. With a very simple assumption, we obtained a meridional circulation consistent with the earlier studies based on radiative transfer computation. The result allowed us to order-estimate the eddy angular-momentum forcing needed to maintain the present super-rotation. We derived the eddy forcing by using cloud-tracking winds and thermal infrared data from Akatsuki. In particular, we focused on the pivotal question on the maintenance of the presentation, which is how the angular momentum (per unit mass) is supplied at its peak around the equatorial cloud top to compensate the deceleration by the meridional circulation. It was revealed that the thermal tides provide it, acting to accelerate the super-rotation, through both the horizontal and the vertical angular-momentum transport. Other waves and large-scale horizontal turbulence are found to counteract it to a weaker degree, in contrast to the earlier expectation from the classical Gierasch-Rossow-Williams mechanism. This study provided a number of by-products, such as the detection of turbulent motion and spectra of wind disturbances. This study was published recently as Horinouchi et al. 2020, Science, 368 (6489), 405-409 and its online supplementary material.

In this paper, a perception–empathy biofeedback (PEBF) system is proposed that supplements the foot pressure status of a paralyzed foot with a wearable vibrotactile biofeedback (BF) vest to the back. Improvements in the ankle dorsiflexion and push-off movement in the swing phase and pre-swing phase, respectively, can be expected after using the proposed system. However, the results of the 3 week pilot clinical tests suggest that significant improvement is only observed for the push-off movement. It is assumed that the attention required to recognize the BF was beyond the ability of the patients. In this paper, a dual task (40 s walking and performing mental arithmetic at the same time) was conducted with the following conditions: no vibrations and providing BF to the lower back and the entire back. According to the results, the ankle joint angle of the paralyzed side at push-off under the entire back condition is statistically significant (p = 0.0780); however, there are no significant changes under the lower back condition (p = 0.4998). Moreover, the ankle joint angle of the paralyzed side at the initial contact is statistically significant with respect to the lower back condition (p = 0.0233) and shows a significant trend for the entire back condition (p = 0.0730). The results suggest that the limited attention capacity of hemiplegic patients fails to improve both dorsiflexion and push-off movements; moreover, ankle motion can be promoted if attention is concentrated on recognizing focalized vibratory feedback patterns.

Contrast-induced encephalopathy (CIE) is a rare complication of contrast agent use. We herein report a case of acute lacunar infarction in a 70-year-old woman. During diagnostic cerebral angiography for asymptomatic common carotid stenosis, she experienced transient drowsiness. After angiography, generalized tonic-clonic seizures occurred in her left arm and leg, with eye deviation to the left. The patient was diagnosed with CIE due to the acute onset of symptoms during angiography and characteristic computed tomography findings of high-density signaling in the cortex. Our findings suggest that it is important to pay close attention to acute neurological symptoms during and immediately after examinations, even with small amounts of contrast agents.

Associations between cognitive decline and cerebral microbleeds (CMBs) have received increasing attention. An association between CMB distribution (deep or lobar) and cognitive decline has been reported, but these findings are controversial. We investigated the association between magnetic resonance imaging (MRI) findings, including CMBs, and cognitive function in patients with first-ever lacunar infarction. We retrospectively included consecutive patients admitted with first-ever lacunar infarction identified by MRI from July 1, 2011, to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after the onset of stroke. The Mini-Mental State Examination (MMSE) was performed within 3 days of admission. We searched the records of 273 patients (age 72.0 ± 11.2 years, 95 females). The median MMSE score was 27 (interquartile range 25.5–29). In a univariate analysis, the MMSE score was associated with age, body mass index (BMI), education, dyslipidemia, chronic kidney disease (CKD), periventricular hyperintensity, medial temporal atrophy, lobar CMBs, and mixed CMBs (p

A triphenylamine with three benzothiophene rings was designed and successfully synthesized in 87% yield. The compound showed absorption at 386 nm and blue emission at around 442 nm, with a fluorescence quantum yield of 0.57. The compound showed high thermostability. The radical cation obtained by one-electron oxidation was stable in solution and showed a significant absorption in the NIR-II region (λmax = 1213 nm). DFT calculations confirmed the experimental data.

Background Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). Research into the cytokine biology of IBD has nurtured the dogmatic view that distinct immunotypes characterize different IBD subtypes. Recently, many biologics have emerged as the treatment options for IBD patients. Still, it is challenging to establish biomarkers for predicting their effectiveness because the cytokines that determine the IBD clinical phenotype vary in individual patients. Therefore, this study aims to explore critical molecules for optimizing treatment by analyzing inflammatory cytokines in the intestinal mucosa of IBD patients. Methods From September 2019, to February 2020, patients with ulcerative colitis (UC) and Crohn’s disease (CD) who underwent colonoscopy or flexible sigmoidoscopy, and the control group, patients who received colorectal polypectomy at our institution, were enrolled in the study. We took biopsies from inflamed ileal or colonic mucosa. We analyzed the gene expression of various inflammatory cytokines by real-time PCR using RT2 Profiler PCR Array (96-Well Format) Human Inflammatory Cytokines & Receptors (QIAGEN). Cytokines not included in this array were subjected to real-time PCR separately. Based on these data, we investigated the relationship between mucosal cytokines and clinical characteristics. Results The total number of patients was 23 (control 5, UC 12, CD 6) cases, the median age was 51 years (18–78), genders were fifteen males and eight females. Disease phenotype was divided into extensive colitis/ left-sided colitis/proctitis (10/1/1) in UC patients, and A1/A2/A3 (2/3/1), L1/L3 (2/4), B1/B1+p/B2/B3 (3/1/1/1) in CD patients. Seven patients were steroid-dependent, and six patients were refractory to the anti-TNFα agent. The higher gene expressions of CCR2/CXCL1/CXCL3/CXCL13, IL-8, IL-33, and SPP1 in inflamed mucosa of UC compared to those of CD (p Conclusion Our results suggest that UC exhibits different cytokine patterns in the intestinal mucosa from CD as reported previously. Exploration of cytokine expressions in the intestinal mucosa may lead to predicting refractory IBD. The identification of molecules that can predict therapeutic effectiveness helps to optimize IBD treatment in the future.

Background Iatrogenic acute aortic dissection (AAD) caused by cardiovascular intervention is rare. Also rare is spontaneous coronary artery dissection (SCAD), a form of acute coronary syndrome, which develops in relatively young women without coronary risk factors. We encountered type A iatrogenic AAD caused by an intervention for SCAD. Case presentation A 53-year-old woman was brought to our hospital after cardiopulmonary resuscitation. She was diagnosed with acute coronary syndrome caused by SCAD, and percutaneous coronary intervention was carried out on her distal left anterior descending artery. The dissection proceeded to the proximal left anterior descending artery and left main coronary artery trunk, so additional percutaneous coronary intervention was performed on the left circumflex artery. After the intervention, type A AAD occurred with a primary entry tear from the left main coronary artery trunk, and computed tomography showed a type A AAD of the aortic arch. We performed emergency ascending aorta replacement and coronary artery bypass grafting to the left anterior descending artery and left circumflex artery. The patient had an uneventful recovery after the operation and was discharged on postoperative day 25. Conclusion To our knowledge, this is the first report of an iatrogenic AAD caused by percutaneous coronary intervention for SCAD.

Gravity waves play essential roles in the terrestrial atmosphere because they propagate far from source regions and transport momentum and energy globally. Gravity waves are also observed in the Venus atmosphere, but their characteristics have been poorly understood. Here we demonstrate activities of small-scale gravity waves using a high-resolution Venus general circulation model with less than 20 and 0.25 km in the horizontal and vertical grid intervals, respectively. We find spontaneous gravity wave radiation from nearly balanced flows. In the upper cloud layer (~70 km), the thermal tides in the super-rotation are primary sources of small-scale gravity waves in the low-latitudes. Baroclinic/barotropic waves are also essential sources in the mid- and high-latitudes. The small-scale gravity waves affect the three-dimensional structure of the super-rotation and contribute to material mixing through their breaking processes. They propagate vertically and transport momentum globally, which decelerates the super-rotation in the upper cloud layer (~70 km) and accelerates it above ~80 km., Gravity waves are observed in Venus atmosphere, but their characteristics are not well-known. Here, the authors show spontaneous generation of gravity waves from the thermal tides in the Venus atmosphere as small-scale gravity waves are resolved in high-resolution general circulation model.

Introduction Poststroke depression (PSD) negatively affects the functional outcome of stroke patients. Patient Health Questionnaire‐9 (PHQ‐9) is a validated screening tool for detecting PSD. This study investigated the relationship between PHQ‐9 score and functional outcomes in stroke patients in a convalescent rehabilitation ward by evaluating functional independence measure (FIM) gain scores and the proportion of patients discharged. Methods In this retrospective study conducted from January 2017 to September 2019, consecutive stroke patients who were admitted to the convalescent rehabilitation ward and could answer PHQ‐9 were assessed. The association between PHQ‐9 scores at the time of admission to the convalescent rehabilitation ward and outcomes (FIM gain score and the proportion of patients discharged) was statistically analyzed. Results Among the 215 patients enrolled in the study, 62 (28.8%) were assessed as having depression, in whom PHQ‐9 scores were 5 or above. Multivariate analysis revealed that the PHQ‐9 score on admission to the convalescent rehabilitation ward was a significant independent factor influencing the FIM gain score (p = .009). In addition, a multivariate analysis revealed that the PHQ‐9 score at the time of admission to the convalescent rehabilitation ward was a significant independent factor influencing the inability to discharge a patient (odds ratio 1.24, 95% confidence interval 1.12–1.39, p, PHQ‐9 score on admission to convalescent rehabilitation ward was an independent significant factor influencing the FIM gain score and the inability to discharge home.

We investigated the association between the results of a simplified cough test and pneumonia onset in 226 patients with acute stroke admitted to Suiseikai Kajikawa Hospital from April to December, 2018. For the simplified cough test, performed on admission, patients orally inhaled a mist of 1% citric acid-physiological saline using a portable mesh nebulizer. When the first cough was evoked or if it remained absent for 30 seconds (indicating an abnormal result), the test was ended. Patients also completed the repetitive saliva swallowing test (RSST) and modified water swallowing test. We monitored patients for pneumonia signs for 30 days post-admission. Eighteen patients exhibited an abnormal simplified cough test result. On multivariate analysis, an abnormal RSST result was independently associated with an abnormal simplified cough test result. Seventeen patients developed pneumonia. The adjusted Cox proportional hazard model for pneumonia onset revealed that the simplified cough test had predictive power for pneumonia onset (hazard ratio, 10.52; 95% confidence interval, 3.72-29.72). The simplified cough test is a strong indicator for predicting the pneumonia development in patients with acute stroke; it should be added to existing bedside screening tests for predicting pneumonia risk, allowing appropriate and timely intervention.

For research domains such as life sciences, which pursue fundamental scientific understanding and applications intended for immediate use, academic entrepreneurship has played a pivotal role in commercialization. This paper presents an evaluation method of researchers related to user-inspired fundamental research, using global databases of startup finances and academic research papers of "startup readiness." Case studies of startups related to biopharmaceutical research topics suggest that the biopharmaceutical field has rich opportunities stemming from scientific research, commercialization, and entrepreneurship. This evaluation method sorts specific industry segments by which financing activities are active, and by which related growing research topics attract increased academic attention. We constructed networks of author citation and co-authorship from paper citation networks related to research topics in industry segments in the biopharmaceutical domain. Results obtained across all research topics we surveyed demonstrated that authors in the top 10% of degree centrality ranking in both networks are far more likely to be startup participants than other authors. Our computational approach might provide convenient, dynamic, global, and real-time understanding of the “startup readiness” of researchers working with research topics for which academic attention is emerging in actively financed biopharmaceutical fields., Business; Computer science; Pharmaceutical science; Biotechnology; Startup readiness; Research-based startups; Paper citation networks; Co-authorship networks; Academic entrepreneurship; Startup finances; Venture capital; User-inspired fundamental research; Technological innovation; Biopharmaceuticals.

The nucleolus is a membrane-less nuclear structure that disassembles when cells undergo mitosis. During mitosis, nucleolar factors are thus released from the nucleolus and dynamically change their subcellular localization; however, their functions remain largely uncharacterised. Here, we found that a nucleolar factor called nucleolar protein 11 (NOL11) forms a protein complex with two tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin in mitotic cells. This complex, referred to here as the NWC (NOL11-WDR43-Cirhin) complex, exists in nucleoli during interphase and translocates to the periphery of mitotic chromosomes, i.e., perichromosomal regions. During mitotic progression, both the congression of chromosomes to the metaphase plate and sister chromatid cohesion are impaired in the absence of the NWC complex, as it is required for the centromeric enrichment of Aurora B and the associating phosphorylation of histone H3 at threonine 3. These results reveal the characteristics of a novel protein complex consisting of nucleolar proteins, which is required for regulating kinetochores and centromeres to ensure faithful chromosome segregation.

The term "oral frailty" reflects the fact that oral health is associated with physical frailty and mortality. The gold standard methods for evaluating the swallowing function have several problems, including the need for specialized equipment, the risk of radiation exposure and aspiration, and general physicians not possessing the requisite training to perform the examination. Hence, several simple and non-invasive techniques have been developed for evaluating swallowing function, such as those for measuring tongue pressure and tongue thickness. The aim of this study was to investigate the relationship between tongue thickness ultrasonography and tongue pressure in the Japanese elderly. We evaluated 254 elderly patients, who underwent tongue ultrasonography and tongue pressure measurement. To determine tongue thickness, we measured the vertical distance from the surface of the mylohyoid muscle to the tongue dorsum using ultrasonography. The results of the analyses revealed that tongue thickness was linearly associated with tongue pressure in both sexes. In male participants, dyslipidemia, lower leg circumference, and tongue pressure were independently and significantly associated with tongue thickness. In female participants, body mass index and tongue pressure were independently and significantly associated with tongue thickness. The optimal cutoff for tongue thickness to predict the tongue pressure of < 20 kPa was 41.3 mm in males, and 39.3 mm in females. In the Japanese elderly, tongue thickness using ultrasonography is associated with tongue pressure. Tongue thickness and tongue pressure, which are sensitive markers for oral frailty, decrease with age. We conclude that tongue ultrasonography provides a less invasive technique for determining tongue thickness and predicts oral frailty for elderly patients.

One of the main sequelae of stroke is dificulty walking, which is characterized by a decreased gait velocity and asymmetrical walking patterns. The purpose of this research was initially focused on developing a vibro-tactile cueing device that recognizes an implicit increase in cadence frequency. Subsequently, a proof-of-concept study with patients who had experienced stroke was conducted to examine the applicability of the system that had been developed. We applied Weber’s law to provide an implicit method for increasing cueing frequency. This law involves the calculation of just-noticeable difference (JND) relative to a previous state. Throughout training with the proposed cueing device, patients marginally increased cadence, and their cadence and gait speeds were significantly increased post-test. Hip circumduction gait (i.e., abnormal gait patterns) did not change significantly throughout training. Notably, patients reported that they were unaware of any changes associated with the vibration stimulus. Our result demonstrates the immediate changes to cadence and gait speed that occurred through training with the proposed implicit cueing device. However, the result of this study is confined to immediate gait changes after training and utilized only a small sample of stroke patients. Thus, the limited volume of data obtained prevents rigorous analysis regarding the applicability of this training method. Nonetheless, these results are promising and provide a starting point from which to base larger studies.

The importance of cultivating learning attitudes that enable learners not only to memorize key facts but also gain insights into the background of these facts is widely recognized. In this study, we aim to develop a novel learning support system that imparts a positive learning attitude to learners by having them perform historical interpretation activities in an exploratory way using historical cartoons as learning materials that are provided to illustrate historical events. In this paper, we propose a historical interpretation activity support system based on cartoon semantics whereby learners can perform self-exploratory learning in a step-by-step manner according to the historical interpretation process model as well as they are provided with support to encourage their historical interpretation activity according to their interests and learning situations. As a result, we confirmed that the system helps promote the learner’s interpretation of history apart from rote learning and has a potential to change their learning attitude of history.

In collaborative learning in a face-to-face environment, participants exchange verbal and non-verbal cues, including gaze and posture. To realize computer-supported collaborative learning (CSCL) systems that treat a form of multiparty multimodal interaction for different purposes according to the learning objective, executing each activity in the CSCL system life-cycle in a continuous and smooth manner is essential. The research objective is to propose an integrated platform as the basis for multimodal interaction-aware CSCL systems. In this paper, we develop a CSCL analysis support environment to support multimodal interaction analysis activities. The environment allows analysts 1) to utilize basic functions that support multimodal interaction analysis without excessive burden and 2) to analyze collaborative learning session data detected from the learning support system on our proposed platform, including verbal and non-verbal information along with developers’ defined learning messages in an integrated way.

The ras oncogene products (H-Ras, K-Ras, and N-Ras) have been regarded as some of the most promising targets for anticancer drug discovery because their activating mutations are frequently found in human cancers. Nonetheless, molecular targeted therapy for them is currently unavailable. Here, we report the discovery of a small-molecule compound carrying a naphthalene ring, named KBFM123, which binds to the GTP-bound form of H-Ras. The solution structure of its complex with the guanosine 5'-(β,γ-imide) triphosphate-bound form of H-RasT35S (H-RasT35S·GppNHp) indicates that the naphthalene ring of KBFM123 interacts directly with a hydrophobic pocket located between switch I and switch II and allosterically inhibits the effector interaction by inducing conformational changes in switch I and its flanking region in strand β2, which are directly involved in recognition of the effector molecules, including c-Raf-1. In particular, Asp38 of H-Ras, a crucial residue for the interaction with c-Raf-1 via the formation of a salt bridge with Arg89 of the Ras-binding domain (RBD) of c-Raf-1, shows a drastic conformational change: its side chain orients toward the opposite direction. Consistent with these results, KBFM123 exhibits an activity to inhibit, albeit weakly, the association of H-RasG12V·GppNHp with the c-Raf-1 RBD. The binding of the naphthalene ring to the hydrophobic pocket of H-RasT35S·GppNHp is further supported by nuclear magnetic resonance analyses showing that two other naphthalene-containing compounds with distinct structures also exhibit similar binding properties with KBFM123. These results indicate that the naphthalene ring could become a promising scaffold for the development of Ras inhibitors.

This paper describes an embodied conversational agent enhanced with specific conversational strategies aiming to foster learners’ readiness towards communication in a second language (L2). Willingness to communicate (WTC) in a second language is believed to have a direct and sustained influence on learners’ actual usage frequency of the target language. To help overcome the lack of suitable environments for increasing L2 learners’ WTC, our approach is to build embodied conversational agents that can help learners surmount their apprehension towards communication in L2. Here, we focus on the dialogue management aspects of our approach and propose a model based on a set of communication strategies (CS) and affective backchannels (AB) to foster such agents’ ability to carry on natural and WTC-friendly conversations with learners. We examined learners’ expected WTC after interacting with one of the following versions of the system: an agent featuring both CS and AB; an agent featuring only CS; and an agent featuring only AB. The results suggested that combining CS and AB empowers the conversational agent and leads to higher expected WTC among L2 learners. We also found that even the AB-only version of the system had the potential to enhance WTC to some extent. These findings are evidence of the feasibility of enhancing L2 learners’ engagement towards communication using a computer-based environment coupled with appropriate conversational strategies.

Highly strained hydrocarbons with two di/tribenzocycloheptatriene units were designed as electrochromic overcrowded ethylenes that undergo reversible interconversion with stable dicationic dyes. Due to severe steric repulsion, two configurational isomers (anti,anti-folded and syn,anti-folded forms) were isolated as stable entities. Photo- and thermal interconversion of these isomers proceeded cleanly: one-way photo-isomerization occurred from anti,anti- to syn,anti-form and one-way thermal isomerization was observed from syn,anti- to anti,anti-form. Even though both isomers undergo two-electron oxidation into the same twisted dications, quite different oxidation potentials enable completely selective oxidation of syn,anti-isomers. Thus, the present multiconfigurational strained hydrocarbons are capable of switching of activation/deactivation of their electrochromic properties by light/heat.