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In recent years, there has been a growing interest in renewable energy resources, which are becoming increasingly popular. With the increase of power generation using distributed energy resources (DER), there is a concern about the lack of inertia in the power system. Virtual synchronous generator (VSG)control is known to improve the stability of the grid by providing virtual inertia to the inverters that link DER to the grid. However, in the event of an accident, the inverter is required to instantaneously generate more power than its rated capacity. When power exceeding the rated power is generated, the inverter may be damaged, and operation cannot be continued. In this paper, the stability of the inverter was verified by setting a power limit above the rated power. As a result, it was found that although it was less than ideal VSG control, it was quicker to return to normal operation than conventional inverters.

OBJECTIVES Lateral medullary infarction mainly impairs the pharyngeal phase of swallowing. We aimed to investigate the utility of the assessment tools of swallowing function in patients with lateral medullary infarction and to determine the factors that could predict the outcomes of swallowing function. MATERIALS AND METHODS 15 patients with lateral medullary infarction who were admitted to Suiseikai Kajikawa Hospital between August 1, 2016, and March 31, 2020 (age 62.7 ± 14.8 years, 5 women) were enrolled in this prospective study. The diagnosis was made using brain magnetic resonance imaging. We analyzed the factors associated with severe swallowing dysfunction, which was defined as the necessity for tube feeding on the 90th day from admission, with multiple logistic regression analysis. RESULTS Multivariate analyses identified the repetitive saliva swallowing test, modified water swallowing test, and vertical spread of stroke lesions as independent significant factors affecting severe swallowing dysfunction (p = 0.002, 0.016, and 0.011, respectively). The sub-scores of the pharyngeal phase of the Mann Assessment of Swallowing Ability were also significantly associated with severe swallowing dysfunction (p < 0.001). However, tongue pressure, severe passage pattern abnormality on videofluoroscopic examination, and vertebral artery dissection were not significantly associated with swallowing dysfunction. CONCLUSIONS Since lateral medullary infarction presents with swallowing dysfunction mainly in the pharyngeal phase, tools that can be used to evaluate the pharyngeal phase of swallowing, such as repetitive saliva swallowing test and modified water swallowing test, are moreuseful than tongue pressure measurement.

Background The onset of carious lesions and periodontal disease originates in plaque formed from dental bacteria. Appropriate plaque control is therefore important. Dental floss is one instrument used to control plaque. The influence of guardians is an important factor in whether children use dental floss regularly. However, the use of dental floss among school-age children and the relationship between use and family background has yet to be examined. Aim In this study, we conducted a questionnaire survey to examine rates of dental floss use and other related factors among elementary school children and their guardians. Methods Surveys were sent to 298 guardians of children in grades 1–6 at an elementary school in Japan and 283 valid responses were received. Statistical analyses were carried out, with child’s use of dental floss as a dependent variable and grade, sex, guardian assistance with child's tooth brushing, frequency of child’s dental check-ups, and guardian's use of dental floss as independent variables. Results The results revealed that 18.4% of children used dental floss compared with 52.7% of guardians, suggesting that the rate of usage among children is much lower than that among guardians. Logistic regression analysis further revealed that guardian's use of dental floss was significantly related to dental floss use among children. Conclusion The guardian's use of dental floss was associated with dental floss use among their children in this group of Japanese elementary school.

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.

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 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.

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.

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".

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

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.

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 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.

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.

Objective In this study, we investigated the determinants of remission and discontinuation of paroxetine pharmacotherapy in outpatients with panic disorder (PD). Methods Subjects were 79 outpatients diagnosed with PD who took 10-40 mg/day of paroxetine for 12 months. The candidate therapeutic determinants included the serotonin transporter gene-linked polymorphic region and the -1019C/G promoter polymorphism of the serotonin receptor 1A as genetic factors, educational background and marital status as environmental factors, and early improvement (EI) at 2 weeks as a clinical factor were assessed. The Clinical Global Impression scale was used to assess the therapeutic effects of the pharmacotherapy. Results Cox proportional hazards regression was performed to investigate the significant predictive factors of remission and discontinuation. EI was only a significant predictive factor of remission. EI was a significant predictive factor of remission (hazard ratio [HR], 2.709; 95% confidence interval [CI], 1.177-6.235). Otherwise, EI and marital status were significant predictive factors of the discontinuation. EI (HR, 0.266; 95% CI, 0.115-0.617) and being married (HR, 0.437; 95% CI, 0.204-0.939) were considered to reduce the risk of treatment discontinuation. In married subjects, EI was a significant predictive factor of the discontinuation (HR, 0.160; 95% CI, 0.045-0.565). However, in unmarried subjects, EI was not a significantly predictive factor for the discontinuation. Conclusion EI achievement appears to be a determinant of PD remission in paroxetine treatment. In married PD patients, EI achievement also appears to reduce a risk of discontinuation of paroxetine treatment.

BACKGROUND Although the survival of patients with cholangiocarcinoma has improved, the prognosis remains unfavorable. The overexpression of mesenchymal-epithelial transition factor (MET) and recepteur d'origine nantais (RON) has been considered to be indicative of a poor prognosis in some types of cancer. On the other hand, some studies have shown that the expression of MET and RON is a favorable prognostic factor in certain types of tumors. MATERIALS AND METHODS Based on the immunohistochemical analysis of MET and RON, 290 patients who underwent resection for extrahepatic cholangiocarcinoma were divided into three groups: MET/RON-negative, -intermediate, and -positive. The associations between MET/RON expression and clinicopathological features, including prognosis, were analyzed. RESULTS MET/RON-negativity was associated with nodal metastasis and advanced pathological stage. The overall 5-year survival rates were significantly lower in the MET/RON-negative and MET/RON-positive groups than in the MET/RON-intermediate group (28.3%, 32.4% and 48.5%, respectively; p=0.01). CONCLUSION The complete loss of one or both MET and RON, as well as their overexpression, is a poor prognostic factor in patients with extrahepatic cholangiocarcinoma, probably due to the high rate of lymph-node metastasis.

This paper presents a method using logistic regression to predict and detect "startup readiness" of researchers in the biopharmaceutical domain, and to suggest determinants to improve their "startup readiness," using databases of start-up finances, research papers, patents, academic organizations, and national socioeconomics. This method sorts specific industry segments by which financing activities are active, and by which related growing research topics attract increased academic attention. In research domains such as the biopharmaceutical field, which include pursuit of fundamental scientific understanding and applications intended for immediate use, abundant startups with intense scientific linkage have attracted venture capital financing and entrepreneurship for further R&D opportunities and commercialization. We hypothesized that variables composed of several features of papers, patents, research institutes, and nations related to this domain can well reflect researchers' "startup readiness." Our logistic regression model based on our selected and constructed explanatory variables yielded good predictive and classifying performance, with an AUC value of 0.73. Results carried specific implications about what variables and their combinations demand attention, to encourage the "startup readiness" of researchers. More than conventional research methods, our computational approach might provide global, comprehensive, but convenient and real-time understanding of the "start-up readiness" of researchers in user-inspired fundamental research.

Haptic-based vibrotactile biofeedback (BF) is a promising technique to improve rehabilitation of balance in stroke patients. However, the extent to which BF training changes temporal structure of the center of pressure (CoP) trajectories remains unknown. This study aimed to investigate the effect of vibrotactile BF training on the temporal structure of CoP during quiet stance in chronic stroke patients using detrended fluctuation analysis (DFA). Nine chronic stroke patients (age; 81.56 ± 44 months post-stroke) received a balance training regimen using a vibrotactile BF system twice a week over 4 weeks. A Wii Balance board was used to record five 30 s trials of quiet stance pre- and post-training at 50 Hz. DFA revealed presence of two linear scaling regions in CoP indicating presence of fast- and slow-scale fluctuations. Averaged across all trials, fast-scale fluctuations showed persistent dynamics (α = 1.05 ± 0.08 for ML and α = 0.99 ± 0.17 for AP) and slow-scale fluctuations were anti-persistent (α = 0.35 ± 0.05 for ML and α = 0.32 ± 0.05 for AP). The slow-scale dynamics of ML CoP in stroke patients decreased from pre-training to post-BF training (α = 0.40 ± 0.13 vs. 0.31 ± 0.09). These results suggest that the vibrotactile BF training affects postural control strategy used by chronic stroke patients in the ML direction. Results of the DFA are further discussed in the context of balance training using vibrotactile BF and interpreted from the perspective of intermittent control of upright stance.

The objective of this research is to use current linked open data (LOD) to generate questions automatically to support history learning. This paper tries to clarify the potential of LOD as a learning resource. By linking LOD to natural language documents, we created an open learning space where learners have access to machine understandable natural language information about many topics. The learning environment supports learners with content-dependent questions. In this paper, we describe the question generation method that creates natural language questions using LOD. The integrated data is combined to a history domain ontology and a history dependent question ontology to generate content-dependent questions. To prove whether the generated questions have a potential to support learning, a human expert conducted an evaluation comparing our automatically generated questions with questions generated manually. The results of the evaluation showed that the generated questions could cover more than 80% of the questions supporting knowledge acquisition generated by humans. In addition, we confirmed the automatically generated questions have a potential to reinforce learners’ deep historical understanding.

Input/output (I/O) devices such as a graphics processing unit and a solid-state drive are inserted into I/O slots of a host in data center platforms. With this sort of configuration the I/O devices are used exclusively by the host with resultant inefficient resource usage. In addition, the maximum number of I/O devices that can be assigned to each host is limited by the number of its I/O slots. This paper proposes a method to solve the resource usage inefficiency and assignment limitation by disaggregating I/O devices from hosts. An I/O device accommodated in a device pool is interconnected with multiple hosts by a standard Ethernet and can be flexibly assigned to one of them. Introducing assignment flexibility of I/O devices among hosts improves the resource usage efficiency and enables as many I/O devices as desired being assigned to each host. The authors further propose a method that enables an I/O device to be simultaneously shared among multiple hosts and multiple I/O packets to be aggregated into an Ethernet frame to suppress the performance overhead of the device disaggregation. Evaluation results showed that I/O devices that are compliant to PCI Express are shared with the overhead up to 27 percent.

Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disorder that is characterized by the selective death of motor neurons. While the fundamental cause of the disorder is still unclear, the first identified risk gene, Cu,Zn superoxide dismutase (SOD1), has led to the proposal of several mechanisms that are relevant to its pathogenesis. These include excitotoxicity, oxidative stress, ER stress, mitochondrial dysfunction, axonal transport disruption, prion-like propagation, and non-cell autonomous toxicity of neuroglia. Recent evidence suggests that the toxicity of the misfolded wild-type SOD1 (SOD1(WT)) is involved in the pathogenesis of sporadic cases. Yet to what extent SOD1 contributes to neurotoxicity in ALS cases generally is unknown. This review discusses the toxic mechanisms of mutant SOD1 (SOD1(mut)) and misfolded SOD1(WT) in the context of ALS as well as the potential implication of these mechanisms in SOD1 mutation-negative ALS.

This paper presents an assessment, using global databases of start-up finances and academic research papers of "start-up readiness" of research topics and researchers related to commercialization-oriented fundamental research. For research domains such as life sciences that pursue fundamental scientific understanding and applications intended for immediate use, academic entrepreneurship has played a pivotal role in commercialization. Case studies of start-ups in the biopharmaceutical research domain suggest that the biopharmaceutical field has abundant opportunities stemming from scientific research, commercialization, and entrepreneurship in life sciences. This assessment 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 the research topics we surveyed demonstrated that authors in the top 10% of degree centrality ranking in both networks are far more likely to be start-up participants than other authors. More than conventional research methods, our computational approach might provide convenient, dynamic comprehensive, global and real-time understanding of "start-up readiness" of research topics and researchers in user-inspired fundamental research.

Pulp regeneration by stem cell transplantation declines due to age-related reduction. We hypothesized that administration of a cytokine together with the cell transplantation may improve the stem cell niche microenvironment and promote regeneration. CCL11 is implicated as a factor in aging. This investigation was performed to investigate the changes in the quality of the regenerated pulp by administration of CCL11 antibody in the aged mice and elucidate the underlying mechanisms.Mobilized dental pulp stem cell (MDPSC) transplants were characterized in an ectopic tooth root transplantation model in both the aged and young mice. The amount of regenerated pulp tissue was analyzed in the transplants with continuous administration of CCL11 antibody compared with those without the antibody administration. Blood CCL11 levels were assessed at the onset of the experiment. Furthermore, immunostaining of CD68 together with CD11c or CD206 for M1 and M2 macrophage, respectively, were performed. Each double-positive cell count of M1 and M2 macrophages and M1/M2 ratio in the transplants with administration were compared with those without administration both in the aged and young mice.The administration of CCL11 antibody enhanced pulp regeneration and significantly reduced the blood CCL11 level in the aged mice. As the number of M1 macrophages decreased, the M1/M2 ratio in the treated aged mouse was less than that in the untreated aged mouse. There was, however, significant difference between the treated aged mouse and the untreated young mouse.CCL11 antibody has the potential to enhance and stimulate pulp regeneration in the aged mice.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD., Inflammatory bowel disease (IBD) is initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Here, the authors show that inhibition of the calreticulin binding to integrin α subunits ameliorates the severity of IBD in animal models.

Takamasa Kinoshita,1,2 Hiroko Imaizumi,1 Hirotomo Miyamoto,1 Utako Okushiba,1 Yuki Hayashi,2 Takashi Katome,2 Yoshinori Mitamura2 1Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan; 2Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan Purpose: To determine the correlation between the changes in metamorphopsia in daily life environment and the M-CHARTS scores after epiretinal membrane (ERM) removal, and to determine the criterion for determining whether clinically significant changes in the metamorphopsia score have occurred in M-CHARTS. Methods: We studied 65 eyes undergoing vitrectomy for unilateral ERM. Self-administered questionnaires were used to examine the metamorphopsia in their daily life. The degree of metamorphopsia was determined by M-CHARTS. The receiver operating characteristic curve was used to determine the best predictor of the changes in metamorphopsia in daily life. To determine the reproducibility of the M-CHARTS score, another set of 56 eyes with ERM was tested twice on two different days. Results: The postoperative changes in the logarithm of the M-CHARTS score was defined as M2-value. The area under the receiver operating characteristic curve for the M2-value as a predictor of the changes in metamorphopsia in daily life was larger than area under the receiver operating characteristic curve obtained for any other parameter. The optimal cutoff value was -0.4. The 95% limits of agreement between test and retest measurements had a reproducibility of ±0.3 logarithm of the M-CHARTS score. Taking into account not only the reproducibility but also the consistency with the subjective changes, we determined the criterion for clinically significant changes in the M-CHARTS scores as a change of the M2-value by ≥0.4. Conclusion: Evaluating the changes in the M-CHARTS scores in logarithmic form is favorable not only theoretically but also from the perspective of consistency with the subjective changes. Keywords: metamorphopsia score, ERM, criterion, vitrectomy&nbsp

Many people would like to live long with healthy body and mind. If you help people live well, you should take psychological stress into account. In this paper, we will support people in the situation of shopping activities. We propose the Shopping Chat Method and let a participant perform shopping along this method. Finally, we consider how to extract “novel” information about shopping activities from participants.