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Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE.

This study investigated the effects of animated food consumption on human psychology. We developed a movable, edible robot and evaluated the participants' impressions induced by the visualization of its movements and eating of the robot. Although several types of edible robots have been developed, to the best of our knowledge, the psychological effects associated with the eating of a robot have not been investigated. We developed a pneumatically driven edible robot using gelatin and sugar. We examined its perceived appearance and the participants' impressions when it was eaten. In the robot-eating experiment, we evaluated two conditions: one in which the robot was moved and one in which it was stationary. Our results showed that participants perceived the moving robot differently from the stationary robot, leading to varied perceptions, when consuming it. Additionally, we observed a difference in perceived texture when the robot was bitten and chewed under the two conditions. These findings provide valuable insights into the practical applications of edible robots in various contexts, such as the medical field and culinary entertainment.

This study examines baseball players' recognition framework of out, ball, and strike counts in baseball games and clarifies the differences in psychological perspectives between batters and pitchers. The participants were 396 players (294 batters and 102 pitchers) belonging to baseball clubs at eight universities. Participants answered 288 questions for all game situations by combining out, ball, and strike counts and runner position. The advantages for batters or pitchers were evaluated using a 7-point Likert scale (from very advantageous for batters to very advantageous for pitchers). Factor analysis indicated four significant factors (36 items): "Batter's advantage count," "Pitcher's advantage count," "2 out young count," and "0 out young count." In a direct comparison of these factors between batters and pitchers, batters were more aware of their advantage over pitchers in the factors "Batter's advantage count" and "0 out young count" and disadvantage in the "Pitcher's advantage count." Significant differences in recognition of these factors were observed between batters and pitchers. Batters were more susceptible to game situations than were pitchers. Our findings suggest that baseball players recognize several types of game situations, although not an infinite number. [ABSTRACT FROM AUTHOR]

BackgroundIt is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC.MethodsElderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more.ResultsWe enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11).ConclusionAlthough several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC.Trial registrationUnique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089.

BackgroundAboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV) infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of comorbidities that increase the risk of HCC in this population is incompletely defined.MethodsThis cross-sectional study was performed in remote tropical Queensland, Australia in January 2021. All individuals living with chronic HBV in the region were identified; the prevalence of relevant comorbidities was determined by reviewing medical records.ResultsAll 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Australians; their median (interquartile range (IQR)) age was 48 (40-62) years; 120/236 (50.9%) were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236 (30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/236 (29.7%) had ≥2 of these additional risk factors for HCC, only 43/236 (18.2%) had none. Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were currently-or had a history of-drinking alcohol hazardously and 5 (26.3%) were current smokers. Patients also had a median (IQR) of 3 (2-4) cardiovascular risk factors (cigarette smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/proteinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities.ConclusionsAboriginal and Torres Strait Islander Australians living with chronic HBV in this region of remote Australia have a high engagement with HBV care and the majority of individuals eligible for antiviral therapy are receiving it. However, a significant comorbidity burden increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate chronic HBV care with management of these comorbidities-rather than focusing on HBV alone-to achieve optimal health outcomes.

International patent classifications (IPCs) are assigned to patent documents; however, since the procedure for assigning classifications is manually done by the patent examiner, it takes a lot of time and effort to select some IPCs from about 70,000 IPCs. Hence, some research has been conducted on patent classification with machine learning. However, patent documents are very voluminous, and learning with all the claims (the part describing the content of the patent) as input would run out of the necessary memory, even if the batch size is set to a very small size. Therefore, most of the existing methods learn by excluding some information, such as using only the first claim as input. In this study, we propose a model that considers the contents of all claims by extracting important information for input. In addition, we focus on the hierarchical structure of the IPC, and propose a new decoder architecture to consider it. Finally, we conducted an experiment using actual patent data to verify the accuracy of the prediction. The results showed a significant improvement in accuracy compared to existing methods, and the actual applicability of the method was also discussed.

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.

Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE. [ABSTRACT FROM AUTHOR]

Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma. [ABSTRACT FROM AUTHOR]

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

Multiple pregnancies pose a high risk of morbidity and mortality in both mothers and infants; thus, obtaining reliable information based on a large population is essential to improve management. We used the maternal and child health statistics, which are published annually, from the database of the Ministry of Health, Labor, and Welfare. The data obtained were aggregated in 5-year intervals, and we used them to analyze the proportion of the number of births for each week of pregnancy to the total of each singleton and multiple pregnancy. For perinatal health indicators (perinatal mortality, stillbirth, and neonatal mortality), the obtained data were calculated and plotted on graphs for each week of pregnancy. Moreover, these indicators were calculated by dividing them into first twin and second twin fetuses. Stillbirth weights were aggregated in several groups, and a histogram was displayed. Between 2000 and 2019, there were 21,068,275 live births, 67,666 stillbirths, and 16,443 early neonatal deaths, excluding 7,148 (7,104 singletons, 44 multiple births) cases, in which the exact gestational weeks at birth were unknown. More than 95% of multiple pregnancies were twin births. Perinatal mortality, stillbirth, and early neonatal mortality rates in multiple pregnancies were the lowest at approximately 37 weeks of gestation and lower than those of single pregnancies at approximately 36 weeks of gestation. Perinatal mortality and stillbirth rates were higher during the delivery of the second twins than the first-born twins, but the early neonatal mortality rate remained approximately the same during the delivery of both twins. As the data in the government database are accumulated and published continuously, indicators can be calculated in the future using the method presented in this study. Further, our findings may be useful for policymaking related to managing multiple pregnancies.

Individuals with high fatigue resistance against a high-intensity conditioning activity (CA) may be able to avoid experiencing significant fatigue and enhance their voluntary performance. We examined whether the optimal contraction duration of dynamic knee extension exercises to maximize subsequent voluntary performance varies depending on the strength level of an individual. The study participants were 22 male American college football players. Initially, all participants performed a 10-s maximal isometric knee extension exercise and were classified as stronger individuals (n = 8) and weaker individuals (n = 8) based on their relative muscle strength. Each group then performed three types of dynamic CA with different contraction durations (6 s [6-CA], 12 s [12-CA], and 18 s [18-CA]) in random order. To observe the time-course changes in post-activation potentiation and performance enhancement, the twitch torques induced by electrical stimulation and isokinetic knee extension torques at 180°/s were recorded before and after each CA. The twitch torque increased at 10 s (29.5% ± 9.3%) and 1 min (18.5% ± 6.8%) after 6-CA for the stronger individuals (p < 0.05). However, no post-activation potentiation was induced in the weaker individuals in either protocol. Voluntary performance increased at 4 (7.0% ± 4.5%) and 7 (8.2% ± 4.3%) min after 18-CA for stronger individuals (p < 0.05). However, there was no post-activation performance enhancement in either protocol for weaker individuals. Thus, CA with a relatively long contraction duration was optimal to maximize the subsequent voluntary performance for stronger individuals. It remains unknown whether CAs performed with relatively short or long contraction durations were optimal for weaker individuals.

Background Strokes are common in people with atrial fibrillation (AF), and can have devastating consequences, especially in the elderly and if AF is untreated. However, community-based studies on screening for untreated AF have not been conducted in Japan, and there has been no evaluation of the effectiveness of early screening for AF in the elderly (≥65 years). Methods The Kyoto Prefectural University of Medicine (KPUM) Education Initiative has conducted an AF awareness campaign consisted of screening tests using a blood pressure (BP) monitor with electrocardiogram (ECG) (the Complete, Omron Healthcare Co., Ltd., Kyoto, Japan) and educational lectures for the elderly (≥65 years) from 2019 to 2020. A modeled effectiveness analysis was performed comparing the life-years and QALYs (quality-adjusted life-years) between direct-acting oral anticoagulation (DOAC)-treated AF and untreated AF in a Japanese setting. The basic description of the Markov model was used for the analysis. Results A total of 1648 participants were screened, and after excluding those with missing information or data (n = 41), 1607 were finally enrolled. The mean (± standard deviation) age of participants was 72.4±5.8 years, 827 (51.5%) were female, 628 (39.1%) had hypertension, and 1368 (85.1%) had CHA2DS2-VASc score ≥2. After cardiologists’ evaluation of all ECG recordings of the Complete, 15 (0.93%) AF were newly detected. For each AF treated with DOAC, 0.859 QALYs gained over the lifetime for 65 years-old men, and 0.856 QALYs for 65 years-old women compared to non-treatment. Conclusion A moderate number of untreated AF were identified in the community-based study. Identification of an increased number of patients with AF, if properly treated with DOAC, ultimately leads to a reduction in the number of strokes occurred over subjects’ lifetime.

Staphylococcus epidermidis is a commensal bacterium in humans. To persist in the bacterial flora of the host, some bacteria produce antibacterial factors such as the antimicrobial peptides known as bacteriocins. In this study, we tried to isolate bacteriocin-producing S. epidermidis strains. Among 150 S. epidermidis isolates from the oral cavities of 287 volunteers, we detected two bacteriocin-producing strains, KSE56 and KSE650. Complete genome sequences of the two strains confirmed that they carried the epidermin-harboring plasmid pEpi56 and the nukacin IVK45-like-harboring plasmid pNuk650. The amino acid sequence of epidermin from KSE56 was identical to the previously reported sequence, but the epidermin synthesis-related genes were partially different. The prepeptide amino acid sequences of nukacin KSE650 and nukacin IVK45 showed one mismatch, but both mature peptides were entirely similar. pNuk650 was larger and had an additional seven ORFs compared to pIVK45. We then investigated the antibacterial activity of the two strains against several skin and oral bacteria and found their different activity patterns. In conclusion, we report the complete sequences of 2 plasmids coding for bacteriocins from S. epidermidis, which were partially different from those previously reported. Furthermore, this is the first report to show the complete sequence of an epidermin-carrying plasmid, pEpi56.

Although it is known that assessment and management of the nutritional status of patients are important for treatment of patients with heart failure (HF), there are currently no established indicators. Therefore, we investigated the effects of nutritional parameters as well as conventional parameters on the prognosis of HF patients. A total of 1954 consecutive HF patients with left ventricular ejection fraction (LVEF) less than 50% were enrolled in this study. Transthoracic echocardiography was performed and conventional parameters for HF patients and parameters to assess nutritional status were measured in all patients. Patients were followed up with a primary endpoint of lethal cardiac events (CEs) for 30.2 months. During the follow-up period, cardiac events were documented in 619 HF patients. The CEs group had a lower level of cholinesterase (201.5U/L vs 265.2U/L, P

Quantum annealing has gained considerable attention because it can be applied to combinatorial optimization problems, which have numerous applications in logistics, scheduling, and finance. In recent years, with the technical development of quantum annealers, research on solving practical combinatorial optimization problems using them has accelerated. However, researchers struggle to find practical combinatorial optimization problems, for which quantum annealers outperform mathematical optimization solvers. Moreover, there are only a few studies that compare the performance of quantum annealers with the state-of-the-art solvers, such as Gurobi and CPLEX. This study determines that quantum annealing demonstrates better performance than the solvers in that the solvers take longer to reach the objective function value of the solution obtained by the quantum annealers for the break minimization problem in a mirrored double round-robin tournament. We also explain the desirable performance of quantum annealing for the sparse interaction between variables and a problem without constraints. In this process, we demonstrate that this problem can be expressed as a 4-regular graph. Through computational experiments, we solve this problem using our quantum annealing approach and two-integer programming approaches, which were performed using the latest quantum annealer D-Wave Advantage, and Gurobi, respectively. Further, we compare the quality of the solutions and the computational time. Quantum annealing was able to determine the exact solution in 0.05 seconds for problems with 20 teams, which is a practical size. In the case of 36 teams, it took 84.8 s for the integer programming method to reach the objective function value, which was obtained by the quantum annealer in 0.05 s. These results not only present the break minimization problem in a mirrored double round-robin tournament as an example of applying quantum annealing to practical optimization problems, but also contribute to find problems that can be effectively solved by quantum annealing.

Expressing emotions through various modalities is a crucial function not only for humans but also for robots. The mapping method from facial expressions to the basic emotions is widely used in research on robot emotional expressions. This method claims that there are specific facial muscle activation patterns for each emotional expression and people can perceive these emotions by reading these patterns. However, recent research on human behavior reveals that some emotional expressions, such as the emotion “intense”, are difficult to judge as positive or negative by just looking at the facial expression alone. Nevertheless, it has not been investigated whether robots can also express ambiguous facial expressions with no clear valence and whether the addition of body expressions can make the facial valence clearer to humans. This paper shows that an ambiguous facial expression of an android can be perceived more clearly by viewers when body postures and movements are added. We conducted three experiments and online surveys among North American residents with 94, 114 and 114 participants, respectively. In Experiment 1, by calculating the entropy, we found that the facial expression “intense” was difficult to judge as positive or negative when they were only shown the facial expression. In Experiments 2 and 3, by analyzing ANOVA, we confirmed that participants were better at judging the facial valence when they were shown the whole body of the android, even though the facial expression was the same as in Experiment 1. These results suggest that facial and body expressions by robots should be designed jointly to achieve better communication with humans. In order to achieve smoother cooperative human-robot interaction, such as education by robots, emotion expressions conveyed through a combination of both the face and the body of the robot is necessary to convey the robot’s intentions or desires to humans.

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months-15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%-46%) and 74% (95% CI, 39%-89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%-77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.

We investigated modality differences in the N2 and P3 components of event-related potentials (ERPs) between somatosensory and auditory Go/No-go paradigms in eighteen healthy prepubescent children (mean age: 125.9±4.2 months). We also evaluated the relationship between behavioral responses (reaction time, reaction time variability, and omission and commission error rates) and amplitudes and latencies of N2 and P3 during somatosensory and auditory Go/No-go paradigms. The peak latency of No-go-N2 was significantly shorter than that of Go-N2 during somatosensory paradigms, but not during auditory paradigms. The peak amplitude of P3 was significantly larger during somatosensory than auditory paradigms, and the peak latency of P3 was significantly shorter during somatosensory than auditory paradigms. Correlations between behavioral responses and the P3 component were not found during somatosensory paradigms. On the other hand, in auditory paradigms, correlations were detected between the reaction time and peak amplitude of No-go-P3, and between the reaction time variability and peak latency of No-go-P3. A correlation was noted between commission error and the peak latency of No-go-N2 during somatosensory paradigms. Compared with previous adult studies using both somatosensory and auditory Go/No-go paradigms, the relationships between behavioral responses and ERP components would be weak in prepubescent children. Our data provide findings to advance understanding of the neural development of motor execution and inhibition processing, that is dependent on or independent of the stimulus modality.

Using event-related potentials (ERPs), we investigated the effects of passive heat stress and recovery on the human cognitive function with Flanker tasks, involving congruent and incongruent stimuli. We hypothesized that modulation of the peak amplitude and latency of the P300 component in ERP waveforms would differ with task difficulty during passive heat stress and recovery. Subjects performed the Flanker tasks before (Pre), at the end of whole body heating (Heat: internal temperature increase of ~1.2°C from the pre-heat baseline), and after the internal temperature had returned to the pre-heat baseline (Recovery). The internal temperature was regulated by a tube-lined suit by perfusing 50°C water for heat stress and 25°C water for recovery immediately after the heat stress. Regardless of task difficulty, the reaction time (RT) was shortened during Heat rather than Pre and Recovery, and standard deviations of RT (i.e., response variability) were significantly smaller during Heat than Pre. However, the peak amplitudes of the P300 component in ERPs, which involved selective attention, expectancy, and memory updating, were significantly smaller during Heat than during Pre, suggesting the impairment of neural activity in cognitive function. Notably, the peak amplitudes of the P300 component were higher during Recovery than during Heat, indicating that the impaired neural activity had recovered after sufficient whole-body cooling. An indicator of the stimulus classification/evaluation time (peak latency of P300) and the RT were shortened during Heat stress, but such shortening was not noted after whole-body cooling. These results suggest that hyperthermia affects the human cognitive function, reflected by the peak amplitude and latency of the P300 component in ERPs during the Flanker tasks, but sufficient treatment such as whole-body cooling performed in this study can recover those functions.

It is difficult for university hospitals to recruit and retain technically efficient surgeons because their missions include teaching and research as well as clinical services. The authors hypothesized that technically efficient surgeons do not continue to provide active clinical services in a university hospital. The authors collected data from all the surgical procedures performed at Teikyo University Hospital from April 1 through September 30 in 2013-2018. The dependent variable was defined as a length of each surgeon's active clinical services measured by month. Data envelopment analysis was employed to calculate each surgeon's technical efficiency score. Five control variables were selected; experience, medical school, surgical volume, gender, and academic ranks. Multiple regression analysis was performed. Efficiency scores had significantly negative association with length of active clinical services. Experience and surgical volume had significantly positive association with length of active clinical services. The other coefficients of control variables were insignificant. Technically efficient surgeons provide shorter active clinical services in a university hospital.

BACKGROUND:Necroptosis is a form of programmed cell death that is accompanied by release of intracellular contents, and reportedly contributes to various diseases. Here, we investigate the significance of necroptosis in pancreatic cancer. METHODS:We used immunohistochemistry and western blot analysis to evaluate expression of the key mediators of necroptosis-receptor-interacting serine/threonine protein kinase 3 (RIP3) and mixed lineage kinase domain-like (MLKL)-in human pancreatic cancer. We also tested the effects of conditioned media (CM) from necroptotic cells on pancreatic cancer cells in Transwell migration and Matrigel invasion assays. Protein array analysis was used to investigate possible mediators derived from necroptotic cells. RESULTS:RIP3 and MLKL are highly expressed in human pancreatic cancer tissues compared with normal pancreas. MLKL expression was particularly intense at the tumor invasion front. CM derived from necroptotic cells promoted cancer cell migration and invasion, but not CM derived from apoptotic cells. C-X-C motif chemokine 5 (CXCL5) was upregulated in CM derived from necroptotic cells compared with CM derived from control or apoptotic cells. Moreover, expression of the receptor for CXCL5, C-X-C-motif chemokine receptor-2 (CXCR2), was upregulated in pancreatic cancer cells. Inhibition of CXCR2 suppressed cancer cell migratory and invasive behavior enhanced by necroptosis. CONCLUSION:These findings indicate that necroptosis at the pancreatic cancer invasion front can promote cancer cell migration and invasion via the CXCL5-CXCR2 axis.

[This corrects the article DOI: 10.1371/journal.pone.0140942.].

Vibration acceleration through whole body vibration has been reported to promote fracture healing. However, the mechanism responsible for this effect remains unclear. Purpose of this study was to determine whether vibration acceleration directly affects cells around the fracture site and promotes endochondral ossification. Four-week-old female Wistar Hannover rats were divided into two groups (vibration [V group] and control [C group]). The eighth ribs on both sides were cut vertically using scissors. From postoperative day 3 to 11, vibration acceleration using Power Plate® (30 Hz, low amplitude [30-Low], 10 min/day) was applied in the V group. Mature calluses appeared earlier in the V group than in the C group by histological analysis. The GAG content in the fracture callus on day 6 was significantly higher in the V group than in the C group. The mRNA expressions of SOX-9, aggrecan, and Col-II in the fracture callus on day 6 and Col-X on day 9 were significantly higher in the V group than in the C group. For in vitro analysis, four different conditions of vibration acceleration (30 or 50 Hz with low or high amplitude [30-Low, 30-High, 50-Low, and 50-High], 10 min/day) were applied to a prechondrogenic cell (ATDC5) and an undifferentiated cell (C3H10T1/2). There was no significant difference in cell proliferation between the control and any of the four vibration conditions for both cell lines. For both cell lines, alcian blue staining was greater under 30-Low and 50-Low conditions than under control as well as 30-High and 50-High conditions on days 7 and 14. Vibration acceleration under 30-L condition upregulated chondrogenic gene expressions of SOX-9, aggrecan, Col-II, and Col-X. Low-amplitude vibration acceleration can promote endochondral ossification in the fracture healing in vivo and chondrogenic differentiation in vitro.

BACKGROUND:The drawback of the delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG) is the presence of intraoperative duodenal injury and postoperative anastomotic stenosis, which can occur due to a relatively short duodenal bulb diameter. MATERIALS AND METHODS:From June 2013 to June 2019, 35 patients with gastric cancer underwent TLDG with a modified DSG consisting of linear stapling and single-layer hand suturing in our institution. All anastomotic procedures were performed by the right hand of the operator positioned between the patient's legs. Linear stapling of the posterior walls of the remnant stomach and duodenum without creating a gap was performed using a 45-mm linear stapler, considering the prevention of intraoperative duodenal injury. The stapler entry hole was closed using a single-layer full-thickness hand suturing technique with knotted sutures and a knotless barbed suture. We described the clinical data and outcomes in the present retrospective patient series. RESULTS:No intraoperative duodenal injury occurred in any of the 35 patients. The median staple length at linear stapling of the posterior walls of the remnant stomach and duodenum was 41.7 ± 4.2 (30-45) mm, and 2 patients (5.7%) had a staple length of 30 mm. There were no incidences of postoperative anastomotic stenosis. CONCLUSIONS:We suggest that a modified DSG consisting of linear stapling and single-layer hand suturing performed by an operator positioned between the patient's legs can be one option for B-Ⅰ reconstruction following TLDG because it can aid in preventing both intraoperative duodenal injury and postoperative anastomotic stenosis.

Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and β-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H2O2) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of β-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.

Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Pa•s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.

Growth hormone (GH) activates multiple signal transduction pathways. To investigate these pathways, we identified novel genes whose transcription was induced by GH in the liver of hypophysectomized (HPX) rats using the suppression subtractive hybridization technique. We found that regulator of calcineurin 1 (Rcan1) mRNA was upregulated by GH administration. RCAN1 regulates the activity of calcineurin, a Ca/calmodulin-dependent phosphatase. Rcan1 encodes two major transcripts, Rcan1-1 and Rcan1-4, resulting from differential promoter use and first exon choice. We found that a single injection of GH increased the levels of Rcan1-4 mRNA and RCAN1-4 protein transiently, but did not increase Rcan1-1 mRNA in HPX rat liver. Then the molecular mechanism of GH to induce Rcan1-4 transcription was examined in rat hepatoma H4IIE cells. Experiments using inhibitors suggested that c-JUN N-terminal kinase was required for the induction of Rcan1-4 mRNA by GH. GH increased the levels of phosphorylated c-JUN protein and c-Jun mRNA in HPX rat liver. The luciferase and electrophoretic mobility shift assays showed that c-JUN upregulated Rcan1-4 mRNA by binding to the cAMP-responsive element in the upstream of Rcan1 exon 4. These results indicate that GH activates c-JUN to affect the activity of calcineurin by the induction of Rcan1-4 in rat liver.

ObjectivesPouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients.Materials and methodsUC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW).ResultsForty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7-47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01-1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31-9.89; P = 0.01).ConclusionsNLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice.

BackgroundFibromyalgia patients experience cardiovascular complications in addition to musculoskeletal pain. This study aimed to investigate the cardiac effects of a prolonged shallow water gait in a fibromyalgia-induced young mouse model.MethodsTo produce a fibromyalgia mouse model, wild-type mice were administered an intraperitoneal injection of reserpine once a day for three days, and two primary experiments were performed. First, three types of gait tests were performed before and after the reserpine injections as follows: (i) 5 minutes of free gait outside the water, (ii) 1 minute of free gait in shallow warm water, and (iii) 5 minutes of free gait in shallow warm water. Second, electrocardiogram recordings were taken before and after the three gait tests. The average heart rate and heart rate irregularity scores were analyzed.ResultsExercise-induced cardiac arrhythmia was observed at 1-minute gait in shallow water during the acute stage of induced FM in young mice. Further, both cardiac arrhythmia and a decrease in HR have occurred at 5-minute gait in shallow water at the same mice. However, this phenomenon was not observed in the wild-type mice under any test conditions.ConclusionAlthough a short-term free gait in shallow warm water may be advantageous for increasing the motor activity of FM-model mice, we should be aware of the risk of prolonged and excessive exercise-induced cardiac arrhythmia. For gait exercises in shallow water as a treatment in FM patients. We suggest a gradual increase in exercise duration may be warranted.

Here, we report a rapid and ultra-sensitive detection technique for fluorescent molecules called scanning single molecular counting (SSMC). The method uses a fluorescence-based digital measurement system to count single molecules in a solution. In this technique, noise is reduced by conforming the signal shape to the intensity distribution of the excitation light via a circular scan of the confocal region. This simple technique allows the fluorescent molecules to freely diffuse into the solution through the confocal region and be counted one by one and does not require statistical analysis. Using this technique, 28 to 62 aM fluorescent dye was detected through measurement for 600 s. Furthermore, we achieved a good signal-to-noise ratio (S/N = 2326) under the condition of 100 pM target nucleic acid by only mixing a hybridization-sensitive fluorescent probe, called Eprobe, into the target oligonucleotide solution. Combination of SSMC and Eprobe provides a simple, rapid, amplification-free, and high-sensitive target nucleic acid detection system. This method is promising for future applications to detect particularly difficult to design primers for amplification as miRNAs and other short oligo nucleotide biomarkers by only hybridization with high sensitivity.

Background: After issuing the "Global action plan on antimicrobial resistance" in 2015, the World Health Organization (WHO) established a priority pathogens list for supporting research and development of novel antimicrobials. We conducted a comprehensive analysis of the WHO priority organisms in a Japanese tertiary hospital to apprehend the local AMR epidemiology. Methods: Data were obtained from electrical medical records in Osaka University Hospital between January 2010 and March 2021. The critical, high, and medium "priority pathogens list" categories of the WHO were used to compare results between the early (2010–2015) and late (2016–2021) phases. Results: Out of 52,130 culture-positive specimens, a total of 9,872 (18.9%) contained WHO priority isolates. In comparison to early phases, late phases were likely to have higher rates of carbapenem resistance in Pseudomonas aeruginosa (15.7% vs 25.0%, P<0.001), 3rd generation cephalosporin resistance in Escherichia coli (11.5% vs 17.8%, P<0.001) as well as Klebsiella pneumoniae (1.6% vs 4.4%, P<0.001), and ampicillin resistance in Haemophilus influenzae (2.4% vs 3.9%, P<0.001). After 2015, however, the proportion of methicillin-resistant and vancomycin-intermediate Staphylococcus aureus was low. In this study, in-hospital mortality was comparable among patients with resistance to the three WHO priority pathogen types: critical (5.9%), high (3.9%), and medium (3.8%), and no significant change was observed between two phases in each category. However, significant interactions for in-hospital mortality were observed in subgroup analyses between "critical priority" AMR and the presence of comorbid conditions, such as chronic kidney disease or diabetes mellitus. Conclusions: To implement better antimicrobial stewardship policies and practices, local priority pathogens and "high-risk" patients for in-hospital death need to be acknowledged and evaluated periodically. [ABSTRACT FROM AUTHOR]

The present study used functional near-infrared spectroscopy (fNIRS), and investigated the differences in neural activation of ipsi- or contralateral hemispheres between right dominant and left non-dominant hands among right-handed subjects using consecutive motor tasks with muscle contraction and relaxation. The subjects performed tasks under four conditions: (1) right hand up (R-Up), (2) left hand up (L-Up), (3) right hand down (R-Down), and (4) left hand down (L-Down). The peak amplitude of oxy-Hb was significantly larger at the contralateral than ipsilateral hemisphere in the premotor area (PM) under the R-Up condition, and no significant differences were observed between contra- and ipsilateral hemispheres under the L-Up condition. In addition, the peak amplitude was more negative at the contra- than ipsilateral hemisphere in the PM under the R-Down condition, while the peak amplitude was significantly more negative at the ipsi- than contralateral hemisphere in the PM under the L-Down condition. These results suggest that the PM of the left hemisphere among right-handed subjects plays an important role in muscle contraction and relaxation with force control.

Atlantoaxial instability (AAI)/subluxation commonly occurs in small breed dogs. Ventral stabilization techniques using screws and/or pins and a plate or, more commonly, polymethylmethacrylate are considered to provide the most favorable outcome. However, the implantation of screws of sufficient sizes for long-term stability becomes challenging in toy breed dogs (e.g.

The present study employed functional magnetic resonance imaging (fMRI) to examine the characteristics of negative blood oxygen level-dependent (Negative BOLD) signals during motor execution. Subjects repeated extension and flexion of one of the following: the right hand, left hand, right ankle, or left ankle. Negative BOLD responses during hand movements were observed in the ipsilateral hemisphere of the hand primary sensorimotor area (SMI), medial frontal gyrus (MeFG), middle frontal gyrus (MFG), and superior frontal gyrus (SFG). Negative BOLD responses during foot movements were also noted in the bilateral hand SMI, MeFG, MFG, SFG, inferior frontal gyrus, middle temporal gyrus, parahippocampal gyrus, anterior cingulate cortex, cingulate gyrus (CG), fusiform gyrus, and precuneus. A conjunction analysis showed that portions of the MeFG and CG involving similar regions to those of the default mode network were commonly deactivated during voluntary movements of the right/left hand or foot. The present results suggest that three mechanisms are involved in the Negative BOLD responses observed during voluntary movements: (1) transcallosal inhibition from the contralateral to ipsilateral hemisphere in the SMI, (2) the deactivated neural network with several brain regions, and (3) the default mode network in the MeFG and CG.

Gliadin, a component of wheat gluten known to be an important factor in the etiology of celiac disease, is related to several other diseases through its enhancing effect on intestinal paracellular permeability. We investigated the significance of gliadin in non-steroidal anti-inflammatory drug (NSAID)-induced small-intestinal damage in mice. 7-week-old C57BL/6 male mice were divided into the following groups: standard diet group, in which mice were fed with wheat-containing standard rodent diet (CE-2); gluten-free diet group, in which mice were fed with gluten-free diet (AIN-76A); and gliadin-administered group, in which mice fed with gluten-free diet were administered with gliadin (~250 mg/kg BW). Each group was subdivided into negative, healthy control group and NSAID-treated group. To some mice fed with gluten-free diet and administered with gliadin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was administered for clarification of the significance of EGFR in NSAID-induced small intestinal damage and intestinal permeability. In mice fed with a gluten-free diet, indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheat-containing standard diet. Gliadin exacerbated the NSAID-induced small-intestinal damage in mice fed with a gluten-free diet. With the administration of indomethacin, MPO activity, a marker of neutrophil infiltration into the mucosa and mRNA expression level of tumor necrosis factor α and interleukin-1β in the small intestine were higher in the gliadin-administered mice. Gliadin increased the intestinal paracellular permeability without indomethacin administration (4.3-fold) and further increased the permeability after indomethacin administration (2.1-fold). Gliadin induced phosphorylation of epidermal growth factor receptor (EGFR) in small-intestinal tissues, and erlotinib (an EGFR tyrosine kinase inhibitor) attenuated the indomethacin-induced intestinal damage and permeability exacerbated by gliadin, accompanied by inhibition of EGFR phosphorylation. These results suggest that gliadin plays an important role in the induction and exacerbation of NSAID-induced small-intestinal damage, and that increase in intestinal permeability via the EGFR signalling pathway is involved in its mechanism.

The food habits of the Asiatic black bear (Ursus thibetanus) are well studied, but there is a little evidence of dietary specialization-that is, when individuals use a narrower set of resources compared to the population as a whole. To examine the dietary composition at the individual level, seasonal patterns of dietary specialization, and sex-based dietary differences in Asiatic black bears, we attached Global Positioning System (GPS) collars to 15 Asiatic black bears and collected their scats in Nagano Prefecture, Japan from 2017 to 2018. Our results showed that the dietary composition differed among individuals, although seasonal changes in dietary composition were observed at the population level. Dietary specialization was high in summer (resources less abundant) and low in spring and autumn (resources more abundant), indicating a relationship with general food abundance and the dietary diversity of bears. In spring, all bears consumed green vegetation and/or seed of Fagaceae family from previous autumn; in early- and late- summer, dietary composition, such as green vegetation, insects, and fruits, greatly differed among individuals. In autumn, most bears heavily depended on seeds of Fagaceae which is high-quality food for bears. Although we did not find statistical differences between sexes in terms of dietary specialization and diversity, we found variations in the timing of feeding on the Fagaceae family, being earlier in females compared with males. We also found considerable variation in dietary composition within sexes, suggesting that dietary specialization depends on multiple factors besides food abundance, food diversity, and sex.

BackgroundThere is no proven management for mild cases of Mycobacterium avium complex (MAC) pulmonary disease, who do not immediately receive treatment and are managed with observation alone, because its long term-natural course, factors predictive of deterioration, and the effect of treating the disease remain unclear. Thus, we sought to investigate the natural course of mild cases of MAC pulmonary disease.MethodsWe conducted a multicenter retrospective study. Sixty-five patients with mild MAC pulmonary disease in whom treatment was withheld for at least 6 months after diagnosis were retrospectively recruited after a review of 747 medical records. Longitudinal changes in clinical features were evaluated by using a mixed effects model.ResultsMean follow-up was 6.9 ± 5.7 years. During the follow-up period, 15 patients (23%) required treatment and 50 (77%) were managed with observation alone. At diagnosis, 65 patients had nodular bronchiectatic disease without fibrocavitary lesions. Among clinical features, mean body mass index (BMI), forced expiratory volume in 1 second as percent of forced vital capacity (%FEV1), nodular lung lesions, and bronchiectasis worsened significantly in the observation group during follow-up. In the treatment group, BMI, and %FEV1 were stable, but bronchiectasis significantly worsened. At diagnosis, the polyclonal MAC infection rate in the treatment group was higher than that in the observation group. Other microbiological factors, such as insertion sequences, did not differ significantly between the groups.ConclusionsMild MAC pulmonary disease progresses slowly but substantially without treatment. Treatment prevents the deterioration of the disease but not the progression of bronchiectasis. Polyclonal MAC infection is a predictor of disease progression.