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Objective. The linear energy transfer (LET) of proton therapy beams increases rapidly from the Bragg peak to the end of the beam. Although the LET can be determined using analytical or computational methods, a technique for efficiently measuring its spatial distribution has not yet been established. Thus, the purpose of this study is to develop a technique to measure the two-dimensional LET distribution in proton therapy in real time using a combination of multiple scintillators with different quenching. Approach. Inorganic and organic scintillator sheets were layered and irradiated with proton beams. Two-color signals of the CMOS sensor were obtained from the scintillation light and calibration curves were generated using LET. LET was calculated using Monte Carlo simulations asLETtandLETdweighted by fluence and dose, respectively. The accuracy of the calibration curve was evaluated by comparing the calculated and measured LET values for the 200 MeV monoenergetic and spread-out Bragg peak (SOBP) beams. LET distributions were obtained from the calibration curves. Main results. The deviation between the calculated and measured LET values was evaluated. For bothLETtandLETd, the deviation in the plateau region of the monoenergetic and SOBP beams tended to be larger than those in the peak region. The deviation was smaller forLETd. In the obtainedLETddistribution, the deviation between the calculated and measured values agreed within 3% in the peak region, while the deviation was larger in other regions. Significance. The LET distribution can be measured with a single irradiation using two scintillator sheets. This method may be effective for verifying LET in daily clinical practice and for quality control., (Creative Commons Attribution license.)

Given the rapid advancement of artificial intelligence, understanding the foundations of intelligent behaviour is increasingly important. Active inference, regarded as a general theory of behaviour, offers a principled approach to probing the basis of sophistication in planning and decision-making. This paper examines two decision-making schemes in active inference based on "planning" and "learning from experience". Furthermore, we also introduce a mixed model that navigates the data complexity trade-off between these strategies, leveraging the strengths of both to facilitate balanced decision-making. We evaluate our proposed model in a challenging grid-world scenario that requires adaptability from the agent. Additionally, our model provides the opportunity to analyse the evolution of various parameters, offering valuable insights and contributing to an explainable framework for intelligent decision-making.

Interpersonal space (IPS) refers to the area surrounding the body in which we engage in social interactions while maintaining our comfort. Numerous previous studies have reported the psychological and physiological changes associated with the proximity of two people engaged in face-to-face interaction. Currently, there is limited knowledge about how the relative position between two socially intimate individuals affects their psychological and physiological states. This research measured the subjective discomfort and electrocardiographic responses of participants when standing static at various relative positions. The highest discomfort, lowest heart rate, and highest heart rate variability (HRV; parasympathetic activity index) were observed when the friend stood in the face-to-face position. Interestingly, heart rate also decreased when the friend stood on the right side, although HRV did not change. We interpreted the results as suggesting that the presence of a familiar person elicits the electrocardiographic responses associated with an increase in parasympathetic activity., (© 2024. The Author(s).)

This paper concerns the distributed intelligence or federated inference that emerges under belief-sharing among agents who share a common world-and world model. Imagine, for example, several animals keeping a lookout for predators. Their collective surveillance rests upon being able to communicate their beliefs-about what they see-among themselves. But, how is this possible? Here, we show how all the necessary components arise from minimising free energy. We use numerical studies to simulate the generation, acquisition and emergence of language in synthetic agents. Specifically, we consider inference, learning and selection as minimising the variational free energy of posterior (i.e., Bayesian) beliefs about the states, parameters and structure of generative models, respectively. The common theme-that attends these optimisation processes-is the selection of actions that minimise expected free energy, leading to active inference, learning and model selection (a.k.a., structure learning). We first illustrate the role of communication in resolving uncertainty about the latent states of a partially observed world, on which agents have complementary perspectives. We then consider the acquisition of the requisite language-entailed by a likelihood mapping from an agent's beliefs to their overt expression (e.g., speech)-showing that language can be transmitted across generations by active learning. Finally, we show that language is an emergent property of free energy minimisation, when agents operate within the same econiche. We conclude with a discussion of various perspectives on these phenomena; ranging from cultural niche construction, through federated learning, to the emergence of complexity in ensembles of self-organising systems., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Empirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli-generated by mixing two hidden sources-neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting., (© 2023. The Author(s).)

Purpose: Contributing to public health by supporting people's health is the social mission of community pharmacists. This multicenter, prospective case series study aimed to evaluate changes in people's behavior and health states through community pharmacists' self-care support for healthy lifestyles., Methods: The participants were recruited from voluntary adults aged ≥20 years who agreed to participate in the study, at community pharmacies in Gifu, Japan, between June and September 2021. Participants self-managed their lifestyles for six months while recording their health data, including blood pressure (BP), daily using devices (home BP monitor, body composition monitor, and activity meter) and a diet-recording app. They received lifestyle modification support at pharmacies at least once per month. Participants' subjective health status, attitudes, and behavioral changes were evaluated using self-report questionnaires. Due to the exploratory nature of this study, data were primarily analyzed descriptively., Results: Fifty-four participants aged 20 to 77 (mean age: 49.6 years; female participant proportion: 55.6%) participated in this study. Their mean weekly BP shifted almost horizontally from baseline to week 24 (systolic BP: 118.8 to 121.5 mmHg; diastolic BP: 76.1 to 77.5 mmHg). At six months, 38.9% and 35.2% of the participants reported better overall health and mental health, respectively, than at baseline. Over 85% of the participants became more proactive in improving their lifestyles regarding salt intake, diet, weight loss, and exercise, although drinking and smoking habits were more challenging to change. All the participants reported that they intended to continue to improve their lifestyle., Conclusion: The participants' responses suggested that community pharmacists' support helped increase participants' health awareness and promote their health-enhancing behaviors. However, its impact on health parameters should be further examined in future studies. More vigorous, tailored self-care support may be worth considering in developing a more effective, community-fitted health/well-being support system in Japan., Competing Interests: Takamasa Nakamura is an employee of Clinical Study Support, Inc. Yoshihito Kato is an employee of Kowa Company, Ltd. Tatsuya Isomura is a board member of Clinical Study Support, Inc. Michiko Hori is a board member of SIC Co., Ltd. The other authors have no conflicts of interest to declare., (© 2023 Hibino et al.)

Objective: The benefit of adding ganglionated plexi ablation to the maze procedure remains controversial. This study aims to compare the outcomes of the maze procedure with and without ganglionated plexi ablation., Methods: This multicenter randomized study included 74 patients with atrial fibrillation associated with structural heart disease. Patients were randomly allocated to the ganglionated plexi ablation group (maze with ganglionated plexi ablation) or the maze group (maze without ganglionated plexi ablation). The lesion sets in the maze procedure were unified in all patients. High-frequency stimulation was applied to clearly identify and perform ganglionated plexi ablation. Patients were followed up for at least 6 months. The primary endpoint was a recurrence of atrial fibrillation., Results: The intention-to-treat analysis included 69 patients (34 in the ganglionated plexi ablation group and 35 in the maze group). No surgical mortality was observed in either group. After a mean follow-up period of 16.3 ± 7.9 months, 86.8% of patients in the ganglionated plexi ablation group and 91.4% of those in the maze group did not experience atrial fibrillation recurrence. Kaplan-Meier atrial fibrillation-free curves showed no significant difference between the two groups (P = .685). Cox proportional hazards regression analysis indicated that left atrial dimension was the only risk factor for atrial fibrillation recurrence (hazard ratio: 1.106, 95% confidence interval 1.017-1.024, P = .019)., Conclusion: The addition of ganglionated plexi ablation to the maze procedure does not improve early outcome when treating atrial fibrillation associated with structural heart disease., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: Dementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donepezil to patients with severe hyposmia can reduce the development of PDD., Methods: This was a multi-centre, randomized, double-blind, parallel group, placebo-controlled trial in patients with non-demented PD with severe hyposmia (The Donepezil Application for Severe Hyposmic Parkinson's Disease [DASH-PD] study). A total of 201 patients were randomly allocated to receive donepezil or placebo in addition to standard therapy for PD. Patients were followed up every 6 months until the onset of PDD or for a maximum of 4 years. The primary endpoint was the onset of dementia. The secondary endpoint was cognitive impairment measured by Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Clinical Dementia Rating (CDR).(UMIN000009958: February 2013 to May 2019)., Findings: A total of 201 hyposmic patients with PD were randomly assigned to a treatment: 103 to donepezil and 98 to placebo. Overall, 141 (70%) patients completed the 4-year intervention. During follow-up, 7 of 103 (6.8%) patients in the donepezil group and 12 of 98 (12.2%) patients in the placebo group developed PDD; however, the hazard ratio of PDD incidence was not statistically significant (hazard ratio (HR), 0.609; 95% confidence interval, 0.240 to 1.547; p  = 0.2969). At week 208, the patients in the donepezil group had better scores on the ACE-R ( p  < 0.005) and the CDR ( p  < 0.005) than those taking placebo., Interpretation: Administration of donepezil to PD patients with severe olfactory dysfunction for 4 years did not change the incidence of dementia but had a beneficial effect on neuropsychological function, with good tolerability., Funding: The Ministry of Health Labour and Welfare and the Japan Agency for Medical Research and Development provided funding for this study., Competing Interests: This study was investigator-initiated and we declare no competing interests. T.B. reports research grants from AbbVie, Co., Ltd., and Eisai, Co., Ltd., Honoraria for lectures from Ono Pharmaceutical Co., Ltd., AbbVie, Co., Ltd., Kyowa Kirin, Co., Ltd., Sumitomo Pharma Co., Ltd., Takeda Pharma, Otsuka Pharma, and Eisai, Co., Ltd., outside the submitted work. AT reports scholarship funds from AbbVie Inc., Eisai, Co., Ltd., Kyowa Kirin, Co., Ltd., and Sumitomo Pharma Co., Ltd. Consulting fees from AbbVie Inc., Kyowa Kirin Co., Ltd., Ono Pharmaceutical Co. Ltd., and Sony Co. Honoraria for lectures from AbbVie Inc., Eizai Co. Ltd., Ono Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., Sumitomo Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd. A.M., T.K. and T.I. have nothing to disclose. E.M. reports Honoraria for lectures from Eisai, and Sumitomo Pharma Co., Ltd. outside the submitted work., (© 2022 The Author(s).)

In Japan, an increasing interest in real-world evidence for hypothesis generation and decision-making has emerged in order to overcome limitations and restrictions of clinical trials. We sought to characterize the context and concrete considerations of when to use Medical Data Vision (MDV) and JMDC databases, the main Japanese real-world data (RWD) sources accessible by pharmaceutical companies. Use cases for these databases, and related issues and considerations, were identified and summarized based on a literature search and experience-based knowledge. Studies conducted using MDV or JMDC were mostly descriptive in nature, or explored potential risk factors by evaluating associations with a target outcome. Considerations such as variable ascertainment at different time points, including issues relating to treatment identification and missing data, were highlighted for these two databases. Although several issues were commonly shared (e.g., only month of event occurrence reported), some database-specific issues were also identified and need to be accounted for. In conclusion, MDV and JMDC present limitations that are relatively typical of RWD sources, though some of them are unique to Japan, such as the identification of event occurrence and the inability to track patients visiting different healthcare settings. Addressing study design and careful result interpretation with respect to the specificities and uniqueness of the Japanese healthcare system is of particular importance. This aspect is especially relevant with respect to the growing global interest of conducting RWD studies in Japan., (© 2022. The Author(s).)

The neuronal substrates that implement the free-energy principle and ensuing active inference at the neuron and synapse level have not been fully elucidated. This Review considers possible neuronal substrates underlying the principle. First, the foundations of the free-energy principle are introduced, and then its ability to empirically explain various brain functions and psychological and biological phenomena in terms of Bayesian inference is described. Mathematically, the dynamics of neural activity and plasticity that minimise a cost function can be cast as performing Bayesian inference that minimises variational free energy. This equivalence licenses the adoption of the free-energy principle as a universal characterisation of neural networks. Further, the neural network structure itself represents a generative model under which an agent operates. A virtue of this perspective is that it enables the formal association of neural network properties with prior beliefs that regulate inference and learning. The possible neuronal substrates that implement prior and posterior beliefs and how to empirically examine the theory are discussed. This perspective renders brain activity explainable, leading to a deeper understanding of the neuronal mechanisms underlying basic psychology and psychiatric disorders in terms of an implicit generative model., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

This work considers a class of canonical neural networks comprising rate coding models, wherein neural activity and plasticity minimise a common cost function-and plasticity is modulated with a certain delay. We show that such neural networks implicitly perform active inference and learning to minimise the risk associated with future outcomes. Mathematical analyses demonstrate that this biological optimisation can be cast as maximisation of model evidence, or equivalently minimisation of variational free energy, under the well-known form of a partially observed Markov decision process model. This equivalence indicates that the delayed modulation of Hebbian plasticity-accompanied with adaptation of firing thresholds-is a sufficient neuronal substrate to attain Bayes optimal inference and control. We corroborated this proposition using numerical analyses of maze tasks. This theory offers a universal characterisation of canonical neural networks in terms of Bayesian belief updating and provides insight into the neuronal mechanisms underlying planning and adaptive behavioural control., (© 2022. The Author(s).)

Background: The use of the left internal thoracic artery (LITA) is the gold standard in coronary artery bypass graft surgery (CABG). Multiarterial grafting for CABG is being increasingly emphasized. This study aimed to resolve the utility of the right internal thoracic artery (RITA) for multiple CABG as "free" RITA and described new evidence., Methods: One hundred sixty-three patients received solo CABG with bilateral internal thoracic arteries between 2005 and 2018. The RITA was used as in situ RITA, group A (n = 62), and the composite graft created with saphenous vein graft (SVG), group B (n = 101). The patency rate and graft size of the composite free RITA and SVG were examined by coronary computed tomography angiography., Results: The average number of distal anastomoses per patient was 3.4 ± 1.0 in group A, and 4.2 ± 1.1 in group B (P < .001). The sequential grafting with free RITA was in 86 patients. The patency rate of both LITA and RITA was similar in both groups. In group B, 40 patients received late computed tomography angiography at a mean of 46 months (range, 17 to 175). The late patency rate was 95.1% in LITA and 96.9% in free RITA. The diameter of free RITA increased from 2.06 ± 0.34 mm to 2.37 ± 0.23 mm (P = .036); that of in situ LITA increased from 2.08 ± 0.51 mm to 2.44 ± 0.49 mm (P = .047); and that of composite SVG decreased from 4.1 ± 0.9 mm to 2.6 ± 0.7 mm (P < .001)., Conclusions: Multiple bypass grafting can be sufficiently achieved with LITA and free RITA. The growth potential of free RITA and in situ LITA might play the important role of expected long-term patency., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Minimally invasive surgery/coronary artery bypass grafting (MICS CABG) via left thoracotomy and multiple CABG is a reported alternative to the standard sternotomy approach. However, harvesting the right internal thoracic artery (RITA) under direct vision requires high surgical skill. We describe MICS CABG with the left internal thoracic artery (LITA) and a composite graft using the in situ right gastroepiploic artery (GEA) and radial artery (RA) to achieve complete coronary revascularization. No complications occurred, and postoperative computed tomography showed patency of all grafts. Our experience suggests that this composite graft can be used safely and effectively in MICS CABG for complete arterial revascularization without difficulty.

Animals make decisions under the principle of reward value maximization and surprise minimization. It is still unclear how these principles are represented in the brain and are reflected in behavior. We addressed this question using a closed-loop virtual reality system to train adult zebrafish for active avoidance. Analysis of the neural activity of the dorsal pallium during training revealed neural ensembles assigning rules to the colors of the surrounding walls. Additionally, one third of fish generated another ensemble that becomes activated only when the real perceived scenery shows discrepancy from the predicted favorable scenery. The fish with the latter ensemble escape more efficiently than the fish with the former ensembles alone, even though both fish have successfully learned to escape, consistent with the hypothesis that the latter ensemble guides zebrafish to take action to minimize this prediction error. Our results suggest that zebrafish can use both principles of goal-directed behavior, but with different behavioral consequences depending on the repertoire of the adopted principles., (© 2021. The Author(s).)

Long-duration spaceflight is associated with an increased risk of urolithiasis, and the pain caused by urinary calculi could result in loss of human performance and mission objectives. The present study investigated the risk of urolithiasis in astronauts during 6 months on the International Space Station, and evaluated whether the suppression of bone resorption by the bisphosphonate, alendronate (ALN), can reduce the risk. A total of 17 astronauts were included into the analysis: exercise using the advanced resistive exercise device (ARED) plus weekly oral 70 mg alendronate (ARED+ALN group, n  = 7) was compared to resistive exercise alone (ARED group, n  = 10). Urine volume decreased in both groups during spaceflight but recovered after return. The ARED group showed increased urinary calcium excretion from the 15th to 30th day of spaceflight, whereas urinary calcium was slightly decreased in the ARED+ALN group. Urinary N-terminal telopeptide (NTX) and helical peptide (HP) of type I collagen, as bone resorption markers, were elevated in the ARED group during and until 0 days after spaceflight, while there was no elevation in these parameters in the ARED+ALN group. Urinary oxalate and uric acid excretion tended to be higher in the ARED group than in the ARED+ALN group during spaceflight. These results demonstrate that astronauts on long-duration spaceflights may be at high risk for the formation of urinary calcium oxalate and calcium phosphate stones through increased urinary excretion of oxalate and uric acid, from degraded type I collagen, as well as of calcium from enhanced bone resorption. Our findings suggest that increased bone resorption during spaceflight, as a risk factor for urinary calculus formation, could be effectively prevented by an inhibitor of bone resorption. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: AO, TM, HO, TI, TK, TY, KK, AL, JS, ES, JJ, and LS have no conflict of interest related to this study., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

For many years, a combination of principal component analysis (PCA) and independent component analysis (ICA) has been used for blind source separation (BSS). However, it remains unclear why these linear methods work well with real-world data that involve nonlinear source mixtures. This work theoretically validates that a cascade of linear PCA and ICA can solve a nonlinear BSS problem accurately-when the sensory inputs are generated from hidden sources via nonlinear mappings with sufficient dimensionality. Our proposed theorem, termed the asymptotic linearization theorem, theoretically guarantees that applying linear PCA to the inputs can reliably extract a subspace spanned by the linear projections from every hidden source as the major components-and thus projecting the inputs onto their major eigenspace can effectively recover a linear transformation of the hidden sources. Then subsequent application of linear ICA can separate all the true independent hidden sources accurately. Zero-element-wise-error nonlinear BSS is asymptotically attained when the source dimensionality is large and the input dimensionality is sufficiently larger than the source dimensionality. Our proposed theorem is validated analytically and numerically. Moreover, the same computation can be performed by using Hebbian-like plasticity rules, implying the biological plausibility of this nonlinear BSS strategy. Our results highlight the utility of linear PCA and ICA for accurately and reliably recovering nonlinearly mixed sources and suggest the importance of employing sensors with sufficient dimensionality to identify true hidden sources of real-world data., (© 2021 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Recent remarkable advances in experimental techniques have provided a background for inferring neuronal couplings from point process data that include a great number of neurons. Here, we propose a systematic procedure for pre- and postprocessing generic point process data in an objective manner to handle data in the framework of a binary simple statistical model, the Ising or generalized McCulloch-Pitts model. The procedure has two steps: (1) determining time bin size for transforming the point process data into discrete-time binary data and (2) screening relevant couplings from the estimated couplings. For the first step, we decide the optimal time bin size by introducing the null hypothesis that all neurons would fire independently, then choosing a time bin size so that the null hypothesis is rejected with the strict criteria. The likelihood associated with the null hypothesis is analytically evaluated and used for the rejection process. For the second postprocessing step, after a certain estimator of coupling is obtained based on the preprocessed data set (any estimator can be used with the proposed procedure), the estimate is compared with many other estimates derived from data sets obtained by randomizing the original data set in the time direction. We accept the original estimate as relevant only if its absolute value is sufficiently larger than those of randomized data sets. These manipulations suppress false positive couplings induced by statistical noise. We apply this inference procedure to spiking data from synthetic and in vitro neuronal networks. The results show that the proposed procedure identifies the presence or absence of synaptic couplings fairly well, including their signs, for the synthetic and experimental data. In particular, the results support that we can infer the physical connections of underlying systems in favorable situations, even when using a simple statistical model.

This letter considers a class of biologically plausible cost functions for neural networks, where the same cost function is minimized by both neural activity and plasticity. We show that such cost functions can be cast as a variational bound on model evidence under an implicit generative model. Using generative models based on partially observed Markov decision processes (POMDP), we show that neural activity and plasticity perform Bayesian inference and learning, respectively, by maximizing model evidence. Using mathematical and numerical analyses, we establish the formal equivalence between neural network cost functions and variational free energy under some prior beliefs about latent states that generate inputs. These prior beliefs are determined by particular constants (e.g., thresholds) that define the cost function. This means that the Bayes optimal encoding of latent or hidden states is achieved when the network's implicit priors match the process that generates its inputs. This equivalence is potentially important because it suggests that any hyperparameter of a neural network can itself be optimized-by minimization with respect to variational free energy. Furthermore, it enables one to characterize a neural network formally, in terms of its prior beliefs.

Direct-gaze signals are known to modulate human cognition, including self-awareness. In the present study, we specifically focused on 'bodily' self-awareness and examined whether direct gaze would modulate one's interoceptive accuracy (IAcc)-the ability to accurately monitor internal bodily sensations. While viewing a photograph of a frontal face with a direct gaze, an averted face or a mere white cross as a baseline, participants were required to count their heartbeats without taking their pulse. The results showed higher IAcc in the direct-gaze condition than in the averted-face or baseline condition. This was particularly the case in participants with low IAcc at baseline, indicating that direct gaze enhanced the participants' IAcc. Importantly, their heart rate was not different while viewing the direct gaze and averted face, suggesting that sensitivity to interoceptive signals, rather than physiological arousal, is heightened by direct gaze. These findings demonstrate the role of social signals in our bodily interoceptive processing and support the notion of the social nature of self-awareness., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

A 79-year-old man underwent repair surgery for a left ventricular free wall rupture after an acute myocardial infarction. The surgical procedure followed for ventricular rupture was according to the rupture type. The patient showed slowly oozing bleeding through small holes. Epicardial echocardiography detected the color signals that crossed the left ventricular wall. Two channels were directly connected from the ventricular cavity to the epicardial hole. Although the bleeding hole was covered with collagen hemostats using a sutureless technique, the bleeding remained, probably because of the pressure exerted by the left ventricle on the channels connected to the epicardial hole. The suture closure technique might be better in cases with channels across the ventricular wall, as detected on echocardiography. We describe a case of left ventricular rupture followed by acute myocardial infarction in which the channel connected to the ruptured ventricular tear was detected on epicardial echocardiography.

To exhibit social intelligence, animals have to recognize whom they are communicating with. One way to make this inference is to select among internal generative models of each conspecific who may be encountered. However, these models also have to be learned via some form of Bayesian belief updating. This induces an interesting problem: When receiving sensory input generated by a particular conspecific, how does an animal know which internal model to update? We consider a theoretical and neurobiologically plausible solution that enables inference and learning of the processes that generate sensory inputs (e.g., listening and understanding) and reproduction of those inputs (e.g., talking or singing), under multiple generative models. This is based on recent advances in theoretical neurobiology-namely, active inference and post hoc (online) Bayesian model selection. In brief, this scheme fits sensory inputs under each generative model. Model parameters are then updated in proportion to the probability that each model could have generated the input (i.e., model evidence). The proposed scheme is demonstrated using a series of (real zebra finch) birdsongs, where each song is generated by several different birds. The scheme is implemented using physiologically plausible models of birdsong production. We show that generalized Bayesian filtering, combined with model selection, leads to successful learning across generative models, each possessing different parameters. These results highlight the utility of having multiple internal models when making inferences in social environments with multiple sources of sensory information.

To propose a concept for correcting the twist between the head and neck and the body frequently occurring in radiotherapy patients and to develop a prototype device for achieving this. Furthermore, the operational accuracy of this device under no load was evaluated. We devised a concept for correcting the twist of patients by adjustment of the three rotation (pitch, roll, and yaw) angles in two independent plates connected by a joint (fulcrum). The two plates (head and neck plate and body plate) rotate around the fulcrum by adjusting screws under each of them. A prototype device was created to materialize this concept. First, after all adjusting screws were set to the zero position, the rotation angle of each plate was measured by a digital goniometer. Repeatability was evaluated by performing 20 repeated measurements. Next, to confirm the rotational accuracy of each plate of the prototype device, the calculated rotation angles for 20 combinations of patterns of traveled distances of the adjusting screws were compared with those measured by the digital goniometer and cone-beam computed tomography (CT). The repeatability (standard deviation: SD) of the pitch, roll, and yaw angles of the head and neck plate was 0.04°, 0.05°, and 0.03°, and the repeatability (SD) of the body plate was 0.05°, 0.04°, and 0.04°, respectively. The mean differences ± SD between the calculated and measured pitch, roll, and yaw angles for the head and neck plate with the digital goniometer were 0.00 ± 0.06°, -0.01 ± 0.06°, and -0.04 ± 0.04°, respectively. The differences for the body plate were -0.03 ± 0.04°, 0.03 ± 0.05°, and 0.02 ± 0.05°, respectively. Results of the cone-beam CT were similar to those of the digital goniometer. The prototype device exhibited good performance regarding the rotational accuracy and repeatability under no load. The clinical implementation of this concept is expected to reduce the residual error of the patient position due to the twist., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objective: We aimed to examine missing data in FFQ and to assess the effects on estimating dietary intake by comparing between multiple imputation and zero imputation., Design: We used data from the Okazaki Japan Multi-Institutional Collaborative Cohort (J-MICC) study. A self-administered questionnaire including an FFQ was implemented at baseline (FFQ1) and 5-year follow-up (FFQ2). Missing values in FFQ2 were replaced by corresponding FFQ1 values, multiple imputation and zero imputation., Setting: A methodological sub-study of the Okazaki J-MICC study.ParticipantsOf a total of 7585 men and women aged 35-79 years at baseline, we analysed data for 5120 participants who answered all items in FFQ1 and at least 50% of items in FFQ2., Results: Among 5120 participants, the proportion of missing data was 3·7%. The increasing number of missing food items in FFQ2 varied with personal characteristics. Missing food items not eaten often in FFQ2 were likely to represent zero intake in FFQ1. Most food items showed that the observed proportion of zero intake was likely to be similar to the probability that the missing value is zero intake. Compared with FFQ1 values, multiple imputation had smaller differences of total energy and nutrient estimates, except for alcohol, than zero imputation., Conclusions: Our results indicate that missing values due to zero intake, namely missing not at random, in FFQ can be predicted reasonably well from observed data. Multiple imputation performed better than zero imputation for most nutrients and may be applied to FFQ data when missing is low.

Animals need to adjust their inferences according to the context they are in. This is required for the multi-context blind source separation (BSS) task, where an agent needs to infer hidden sources from their context-dependent mixtures. The agent is expected to invert this mixing process for all contexts. Here, we show that a neural network that implements the error-gated Hebbian rule (EGHR) with sufficiently redundant sensory inputs can successfully learn this task. After training, the network can perform the multi-context BSS without further updating synapses, by retaining memories of all experienced contexts. This demonstrates an attractive use of the EGHR for dimensionality reduction by extracting low-dimensional sources across contexts. Finally, if there is a common feature shared across contexts, the EGHR can extract it and generalize the task to even inexperienced contexts. The results highlight the utility of the EGHR as a model for perceptual adaptation in animals.

This paper considers the emergence of a generalised synchrony in ensembles of coupled self-organising systems, such as neurons. We start from the premise that any self-organising system complies with the free energy principle, in virtue of placing an upper bound on its entropy. Crucially, the free energy principle allows one to interpret biological systems as inferring the state of their environment or external milieu. An emergent property of this inference is synchronisation among an ensemble of systems that infer each other. Here, we investigate the implications of neuronal dynamics by simulating neuronal networks, where each neuron minimises its free energy. We cast the ensuing ensemble dynamics in terms of inference and show that cardinal behaviours of neuronal networks - both in vivo and in vitro - can be explained by this framework. In particular, we test the hypotheses that (i) generalised synchrony is an emergent property of free energy minimisation; thereby explaining synchronisation in the resting brain: (ii) desynchronisation is induced by exogenous input; thereby explaining event-related desynchronisation and (iii) structure learning emerges in response to causal structure in exogenous input; thereby explaining functional segregation in real neuronal systems.

Objectives: The postoperative left ventricular end-systolic volume index and ejection fraction are benchmarks of surgical ventricular reconstruction but remain unpredictable. This study aimed to identify who could be associated with a higher long-term survival by adding surgical ventricular reconstruction to coronary artery bypass grafting than coronary artery bypass grafting alone (responders to surgical ventricular reconstruction)., Methods: The subjects were 293 patients (median age, 63 years; 255 men) who underwent coronary artery bypass grafting for ischemic heart disease with left ventricular dysfunction in 16 cardiovascular centers in Japan. The relationships among surgical ventricular reconstruction, postoperative end-systolic volume index, ejection fraction, and survival were analyzed to identify responders to surgical ventricular reconstruction., Results: Surgical ventricular reconstruction was performed in 165 patients (56%). The end-systolic volume index and ejection fraction significantly improved (end-systolic volume index, 91 to 64 mL/m 2 ; ejection fraction, 28% to 35%) for all patients. The postoperative end-systolic volume index and ejection fraction were estimated, and surgical ventricular reconstruction was found to be significantly associated with both end-systolic volume index (14.5 mL/m 2 reduction, P < .001) and ejection fraction (3.1% increase, P = .003). During the median follow-up of 6.8 years, 69 patients (24%) died. Only the postoperative ejection fraction was significantly associated with survival (hazard ratio, 0.925; 95% confidence interval, 0.885-0.968), although this effect was limited to those with postoperative end-systolic volume index of 40 to 80 mL/m 2 in the subgroup analysis (hazard ratio, 0.932; 95% confidence interval, 0.894-0.973)., Conclusions: Adding surgical ventricular reconstruction to coronary artery bypass grafting could reduce the mortality risk by increasing ejection fraction for those with a postoperative end-systolic volume index within a specific range. The postoperative end-systolic volume index could demarcate responders to surgical ventricular reconstruction, and its estimation can help in surgical decision making., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

In this work, we address the neuronal encoding problem from a Bayesian perspective. Specifically, we ask whether neuronal responses in an in vitro neuronal network are consistent with ideal Bayesian observer responses under the free energy principle. In brief, we stimulated an in vitro cortical cell culture with stimulus trains that had a known statistical structure. We then asked whether recorded neuronal responses were consistent with variational message passing based upon free energy minimisation (i.e., evidence maximisation). Effectively, this required us to solve two problems: first, we had to formulate the Bayes-optimal encoding of the causes or sources of sensory stimulation, and then show that these idealised responses could account for observed electrophysiological responses. We describe a simulation of an optimal neural network (i.e., the ideal Bayesian neural code) and then consider the mapping from idealised in silico responses to recorded in vitro responses. Our objective was to find evidence for functional specialisation and segregation in the in vitro neural network that reproduced in silico learning via free energy minimisation. Finally, we combined the in vitro and in silico results to characterise learning in terms of trajectories in a variational information plane of accuracy and complexity.

Humans have flexible control over cognitive functions depending on the context. Several studies suggest that the prefrontal cortex (PFC) controls this cognitive flexibility, but the detailed underlying mechanisms remain unclear. Recent developments in machine learning techniques allow simple PFC models written as a recurrent neural network to perform various behavioral tasks like humans and animals. Computational modeling allows the estimation of neuronal parameters that are crucial for performing the tasks, which cannot be observed by biologic experiments. To identify salient neural-network features for flexible cognition tasks, we compared four PFC models using a context-dependent integration task. After training the neural networks with the task, we observed highly plastic synapses localized to a small neuronal population in all models. In three of the models, the neuronal units containing these highly plastic synapses contributed most to the performance. No common tendencies were observed in the distribution of synaptic strengths among the four models. These results suggest that task-dependent plastic synaptic changes are more important for accomplishing flexible cognitive tasks than the structures of the constructed synaptic networks.

The mutual information between the state of a neural network and the state of the external world represents the amount of information stored in the neural network that is associated with the external world. In contrast, the surprise of the sensory input indicates the unpredictability of the current input. In other words, this is a measure of inference ability, and an upper bound of the surprise is known as the variational free energy. According to the free-energy principle (FEP), a neural network continuously minimizes the free energy to perceive the external world. For the survival of animals, inference ability is considered to be more important than simply memorized information. In this study, the free energy is shown to represent the gap between the amount of information stored in the neural network and that available for inference. This concept involves both the FEP and the infomax principle, and will be a useful measure for quantifying the amount of information available for inference.

Recently, in Japan, the J Graft Open Stent Graft (JOSG) was commercialized for surgical repair of an aortic aneurysm and aortic dissection and the frozen elephant trunk technique was applied. Kinking of the JOSG is a rare adverse event that requires additional intervention. We experienced 2 patients who developed kinking of a JOSG after translocated total arch replacement with the frozen elephant trunk technique for acute Type A aortic dissection. Both patients had intermittent claudication with a decreased ankle-brachial pressure index after the operation. Computed tomography angiography showed kinking between the non-stent and stent parts of the JOSG. Therefore, we performed endovascular repair. A severely angulated arch preserved by a translocated technique may lead to kinking of a JOSG. This suggests that the removed non-stent part should be as short as possible to prevent kinking of the JOSG.

Oral lichen planus (OLP) is an autoimmune inflammatory disease of the oral mucosa whose etiology remains unknown. Moreover, the possibility of OLP being a premalignant change is under debate. Various types of immune cells infiltrate the OLP lesion and affect its clinicopathological features. However, the diversity of infiltrating immune cells has not been fully clarified in relation to OLP diagnosis. In this study, we quantitatively examined CD8+ lymphocyte infiltration by immunohistochemistry, which is the principal effector of cytotoxic immune reaction in 123 cases of OLP specimens. Our examination revealed that high-grade intraepithelial CD8+ lymphocyte infiltration was associated with a high remission rate. Evaluation of the infiltration of T-bet+ and FoxP3+ lymphocytes, which corresponded to the Th1 and Treg CD4+ subsets, respectively, showed that intraepithelial CD8+ lymphocytes were associated with the remission rate in the subgroup with a higher T-bet/FoxP3 subset balance that is inducible for cytotoxic immunity. We also investigated the cutoff value of CD8+ lymphocyte infiltration for histopathological diagnosis. By microscopic counting, 16 cells/high-power field, which was also confirmed in the validation cohort, was established as the cutoff value for intraepithelial CD8+ lymphocyte infiltration for predicting the remission of OLP. Remitting OLP might be different from refractory OLP in terms of etiology and clinical behavior. Thus, intraepithelial CD8+ lymphocytes may serve not only as a predictive biomarker for remission but also as an area for further biomedical research regarding the etiology and premalignant potential of OLP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Synthetic accessibility evaluation is a process to assess the ease of synthesis of compounds. A rapid method for the assessment of synthetic accessibility for a vast number of chemical compounds is expected to bring about a breakthrough in the drug discovery. Although several computational methods have been proposed, the compound evaluation has still been processed by medicinal chemists; however, the low throughput of the human evaluation due to the lack of chemists is a critical issue for handling a large number of compounds. We propose the use of crowdsourcing for addressing this problem, and we conducted experiments to investigate the feasibility of incorporating semi-experts and a statistical aggregation method into the synthetic accessibility evaluation. Our experimental results show that we can obtain accurate synthetic accessibility scores through the statistical aggregation of judgments from semi-experts., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We developed a biologically plausible unsupervised learning algorithm, error-gated Hebbian rule (EGHR)-β, that performs principal component analysis (PCA) and independent component analysis (ICA) in a single-layer feedforward neural network. If parameter β = 1, it can extract the subspace that major principal components span similarly to Oja's subspace rule for PCA. If β = 0, it can separate independent sources similarly to Bell-Sejnowski's ICA rule but without requiring the same number of input and output neurons. Unlike these engineering rules, the EGHR-β can be easily implemented in a biological or neuromorphic circuit because it only uses local information available at each synapse. We analytically and numerically demonstrate the reliability of the EGHR-β in extracting and separating major sources given high-dimensional input. By adjusting β, the EGHR-β can extract sources that are missed by the conventional engineering approach that first applies PCA and then ICA. Namely, the proposed rule can successfully extract hidden natural images even in the presence of dominant or non-Gaussian noise components. The results highlight the reliability and utility of the EGHR-β for large-scale parallel computation of PCA and ICA and its future implementation in a neuromorphic hardware.

Background: Synchrony within neuronal networks is thought to be a fundamental feature of neuronal networks. In order to quantify synchrony between spike trains, various synchrony measures were developed. Most of them are time scale dependent and thus require the setting of an appropriate time scale. Recently, alternative methods have been developed, such as the time scale independent SPIKE-distance by Kreuz et al., New Method: In this study, a novel time-scale independent spike train synchrony measure called Spike-contrast is proposed. The algorithm is based on the temporal "contrast" (activity vs. non-activity in certain temporal bins) and not only provides a single synchrony value, but also a synchrony curve as a function of the bin size., Results: For most test data sets synchrony values obtained with Spike-contrast are highly correlated with those of the SPIKE-distance (Spearman correlation value of 0.99). Correlation was lower for data containing multiple time scales (Spearman correlation value of 0.89). When analyzing large sets of data, Spike-contrast performed faster., Comparison of Existing Method: Spike-contrast is compared to the SPIKE-distance algorithm. The test data consisted of artificial spike trains with various levels of synchrony, including Poisson spike trains and bursts, spike trains from simulated neuronal Izhikevich networks, and bursts made of smaller bursts (sub-bursts)., Conclusions: The high correlation of Spike-contrast with the established SPIKE-distance for most test data, suggests the suitability of the proposed measure. Both measures are complementary as SPIKE-distance provides a synchrony profile over time, whereas Spike-contrast provides a synchrony curve over bin size., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Invasive ductal carcinomas of breast with marked stromal lymphocytic infiltration have come to be classified as lymphocyte-predominant breast cancer (LPBC) because it obtains high pathological complete response rates with neoadjuvant chemotherapy. Medullary carcinoma (MC), which is independent from LPBC, is a rare histological subtype of invasive breast carcinoma accompanied by abundant lymphoplasmacytic infiltration as LPBC. Although MC shows marked cellular and structural atypia, it usually has a favorable outcome. It is occasionally difficult to distinguish MC from LPBC because both subtypes have nonspecific morphological features according to the present diagnostic criteria. Herein, we adopted multiplexed fluorescent immunohistochemistry to perform quantitative and simultaneous analyses of tumor-infiltrating lymphocytes (TILs) considering their spatial distribution and examined focal immune reaction differences between MC and LPBC. We found that CD8+ TILs are predominant in the intratumoral region, whereas CD4+ TILs are less common in MC. In non-luminal-type cancers, the numbers of stromal and intratumoral CD8+ TILs were significantly higher in MC than in LPBC. Stratified analyses by CD4+ TIL subsets showed robust infiltration of intratumoral CD8+ TILs in non-luminal-type MC even in suppressive environments, such a low T helper 1-to-regulatory T cell ratio. Our results suggest that extensive intratumoral CD8+ TIL infiltration might well be a promising biomarker for distinguishing MC from LPBC, especially in non-luminal-type cancers. Intratumoral CD8+ TILs and nonluminal intrinsic subtypes may serve as diagnostic characteristics allowing reliable histological criteria to be established for reproducibly diagnosing MC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Adult neurogenesis in the hippocampus facilitates cognitive functions such as pattern separation in mammals. However, it remains unclear how newborn neurons mediate changes in neural networks to enhance pattern separation ability. Here, we developed an in vitro model of adult neurogenesis using rat hippocampal cultures in order to investigate whether newborn neurons can be directly incorporated into neural networks related to pattern separation to produce functional improvements., Method: We optimized at schedule of basic fibroblast growth factor (bFGF) administration to enhance neurogenesis, and then used a microelectrode array system to evaluate the responses of neural cultures to two different spatial pattern stimuli (L and inverted L shapes) before and after training., Results: We found that early synaptic response times to a given pattern were shortened after training, and that this effect was more pronounced in cultures treated with bFGF. Furthermore, bFGF-treated cultures showed improved response specificity after training as indicated by calculated Kullback-Leibler divergence values, suggesting that pattern separation was better achieved in cultures with enhanced neurogenesis., Conclusion: Neural networks containing greater numbers of immature neurons exhibited higher response specificity to spatial pattern stimulation, suggesting the improvement of the pattern separation by neurogenesis enhancement., Significance: These results are the first in vitro demonstration that neurogenesis improves pattern separation. Our novel in vitro system will be a useful tool for investigating the contribution of adult neurogenesis to cognitive functions.

Synaptic plasticity is a central theme in neuroscience. A framework of three-factor learning rules provides a powerful abstraction, helping to navigate through the abundance of models of synaptic plasticity. It is well-known that the dopamine modulation of learning is related to reward, but theoretical models predict other functional roles of the modulatory third factor; it may encode errors for supervised learning, summary statistics of the population activity for unsupervised learning or attentional feedback. Specialized structures may be needed in order to generate and propagate third factors in the neural network., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To assess the psychometric properties of the Japanese version of the Revised Fibromyalgia Impact Questionnaire (JFIQR) in fibromyalgia (FM) patients., Method: The reliability and validity of the JFIQR were assessed using online data collected from Japanese FM patients. Reliability was evaluated based on test-retest reliability results and internal consistency; validity was evaluated on the basis of concurrent and known-group validity., Results: A total of 105 patients completed the online questionnaire. Intra-class correlation coefficients for test-retest were 0.91 for the JFIQR total score with a range of 0.84-0.90 in three domains: function, overall impact and symptoms. Internal consistency results indicated a Cronbach's alpha of 0.90 for the total score with a range of 0.83 and 0.85 for the domains. Concurrent validity results showed that the total score was correlated to all external criteria (Japanese version of the Fibromyalgia Impact Questionnaire, Fibromyalgia Activity Scale-31, Medical Outcomes Study 36-item Short-Form health survey) from a moderate to strong degree with most indicating a strong correlation. Results of known-group validity showed that the JFIQR total score is capable of discriminating between FM and the other groups, such as rheumatic arthritis and no chronic pain (P < 0.0001 for all pairwise comparisons)., Conclusion: The current psychometric assessment of the JFIQR demonstrated that it is a reliable and valid questionnaire in Japanese patients with FM. Usefulness of the JFIQR in clinical studies and medical practice for Japanese-speaking populations is expected., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Over the last few decades, because of the significant development of anion exchange membranes, increasing efforts have been devoted the realization of anion exchange membrane fuel cells (AEMFCs) that operate with the supply of hydrogen generated on-site. In this paper, ammonia was selected as a hydrogen source, following which the effect of conceivable impurities, unreacted NH 3 and atmospheric CO 2 , on the performance of AEMFCs was established. As expected, we show that these impurities worsen the performance of AEMFCs significantly. Furthermore, with the help of in situ attenuated total reflection infrared (ATR-IR) spectroscopy, it was revealed that the degradation of the cell performance was primarily due to the inhibition of the hydrogen oxidation reaction (HOR). This is attributed to the active site occupation by CO-related adspecies derived from (bi)carbonate adspecies. Interestingly, this degradation in the HOR activity is suppressed in the presence of both NH 3 and HCO 3 - because of the bicarbonate ion consumption reaction induced by the existence of NH 3 . Further analysis using in situ ATR-IR and electrochemical methods revealed that the poisonous CO-related adspecies were completely removed under NH 3 -HCO 3 - conditions, accompanied by the improvement in HOR activity. Finally, a fuel cell test was conducted by using the practical AEMFC with the supply of NH 3 -contained H 2 gas to the anode and ambient air to the cathode. The result confirmed the validity of this positive effect of NH 3 -HCO 3 - coexistence on CO 2 -tolerence of AEMFCs. The cell performance achieved nearly 95% of that without any impurity in the fuels. These results clearly show the impact of the chemically induced bicarbonate ion consumption reaction on the realization of highly CO 2 -tolerent AEMFCs.

Background: Most studies of risk factors for new low back pain (LBP) have been conducted in Western populations, but because of cultural and environmental differences, the impact of causal factors may not be the same in other countries. We used longitudinal data from the Cultural and Psychosocial Influences on Disability (CUPID) study to assess risk factors for new onset of disabling LBP among Japanese workers., Methods: Data came from a 1-year prospective follow-up of nurses, office workers, sales/marketing personnel, and transportation workers, initially aged 20-59 years, who were employed in or near Tokyo. A baseline questionnaire included items on past history of LBP, personal characteristics, ergonomic work demands, and work-related psychosocial factors. Further information about LBP was collected at follow-up. Analysis was restricted to participants who had been free from LBP during the 12 months before baseline. Logistic regression was used to assess baseline risk factors for new onset of disabling LBP (i.e. LBP that had interfered with work) during the 12 months of follow-up., Results: Among 955 participants free from LBP during the 12 months before baseline, 58 (6.1%) reported a new episode of disabling LBP during the 12-month follow-up period. After mutual adjustment in a multivariate logistic regression analysis, which included the four factors that showed associations individually (p < 0.1) in analyses adjusted only for gender and age, the highest odds ratio (OR) was for past history of LBP (2.8, 95% [confidence interval {CI}]: 1.6-4.9), followed by working ≥60 h per week (1.8, 95% CI: 1.0-3.5) and lifting weights ≥25 kg by hand (1.6, 95% CI: 0.9-3.0). When past history of LBP was excluded from the model, ORs for the remaining risk factors were virtually unchanged., Conclusions: Our findings suggest that among Japanese workers, as elsewhere, past history of LBP is a major risk factor for the development of new episodes of disabling back pain. They give limited support to the association with occupational lifting that has been observed in earlier research, both in Japan and in Western countries. In addition, they suggest a possible role of long working hours, which merits further investigation.

Objective: We aimed to assess the diagnostic utility of the linguistically validated Japanese version of the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS-J) as a screening tool for neuropathic pain in the clinical setting., Methods: Patients with neuropathic pain or nociceptive pain who were 20 to 85 years of age were included. Sensitivity and specificity using the original cutoff value of 12 were assessed to evaluate the diagnostic utility of the LANSS-J. Sensitivity and specificity with possible cutoff values were calculated, along with area under the receiver operating characteristic curve. We then evaluated agreement regarding assessment of the LANSS-J by two investigators. We used the intraclass correlation coefficient (ICC) for the total score and Cohen's kappa coefficient for each item., Results: Data for patients with neuropathic pain (n = 30) and those with nociceptive pain (n = 29) were analyzed. With a cutoff of 12, the sensitivity was 63.3% (19/30) and the specificity 93.1% (27/29). Sensitivity improved substantially with a cutoff of ≤ 11 (≥ 83.3%, 25/30). High specificity (93.1%, 27/29) was sustained with a cutoff of 9 to 12. The ICC for the total score was 0.85, indicating sufficient agreement. Kappa coefficients ranged from 0.68 to 0.84., Conclusions: The LANSS-J is a valid screening tool for detecting neuropathic pain. Our results suggest that employing the original cutoff value provides high specificity, although a lower cutoff value of 10 or 11 (with its high specificity maintained) may be more beneficial when pain attributed to neuropathic mechanisms is suspected in Japanese patients., (© 2016 World Institute of Pain.)

Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period. However, the relationship among these phenomena remains unclear because it is difficult to experimentally show how the developmental shift of inhibitory transmission influences neural activities and whether the activities promote synapse elimination and neurite pruning. In this study, we modeled synapse elimination in neuronal circuits using the modified Izhikevich's model with functional shifting of GABAergic transmission. The simulation results show that synaptic pruning within a specified period like the critical period is spontaneously generated as a function of the developmentally shifting inhibitory transmission and that the specific firing rate and increasing synchronization of neural circuits are seen at the initial stage of the critical period. This temporal relationship was experimentally supported by an in vitro primary culture of rat cortical neurons in a microchannel on a multi-electrode array (MEA). The firing rate decreased remarkably between the 18-25 days in vitro (DIV), and following these changes in the firing rate, the neurite density was slightly reduced. Our simulation and experimental results suggest that decreasing neural activity due to developing inhibitory synaptic transmission could induce synapse elimination and neurite pruning at particular time such as the critical period. Additionally, these findings indicate that we can estimate the maturity level of inhibitory transmission and the critical period by measuring the firing rate and the degree of synchronization in engineered neural networks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of computational molecular design is the identification of promising hypothetical molecules with a predefined set of desired properties. We address the issue of accelerating the material discovery with state-of-the-art machine learning techniques. The method involves two different types of prediction; the forward and backward predictions. The objective of the forward prediction is to create a set of machine learning models on various properties of a given molecule. Inverting the trained forward models through Bayes' law, we derive a posterior distribution for the backward prediction, which is conditioned by a desired property requirement. Exploring high-probability regions of the posterior with a sequential Monte Carlo technique, molecules that exhibit the desired properties can computationally be created. One major difficulty in the computational creation of molecules is the exclusion of the occurrence of chemically unfavorable structures. To circumvent this issue, we derive a chemical language model that acquires commonly occurring patterns of chemical fragments through natural language processing of ASCII strings of existing compounds, which follow the SMILES chemical language notation. In the backward prediction, the trained language model is used to refine chemical strings such that the properties of the resulting structures fall within the desired property region while chemically unfavorable structures are successfully removed. The present method is demonstrated through the design of small organic molecules with the property requirements on HOMO-LUMO gap and internal energy. The R package iqspr is available at the CRAN repository.

Congestive heart failure (CHF) is one of the major causes of death and occurs in more than 15,000,000 patients worldwide. The incidence is expected to increase in parallel with the aging population. Most current therapies for CHF are medications, and biventricular pacing implantation as appropriated by cardiologists, or surgical interventions. The heart transplantation for indicated patients is still gold standard surgery although the 10-year survival rate is approximately 60% based on the worldwide data. However, the cardiac transplantation remains epidemiologically insignificant because of donor pool limitations. New strategies for treating CHF are needed. In addition to conventional cardiac surgery, surgical ventricular restoration was reported as a promising surgical therapy in 1990s. After the first report of partial left ventriculectomy in which posterior wall was widely resected for dilated heart, many controversial clinical and animal research studies have been reported. In this review, the principles of posterior cardiac restoration therapy will be discussed. An overview of posterior cardiac restoration, structure, and torsion are presented. By understanding the structure of cardiac muscle, shape, and torsion of left ventricle for surgical restoration, the procedure can be performed based on appropriate indication and this knowledge can be used to optimize and improve its efficacy. The use of mechanical support devices has recently become commonplace in many centers, and the use of implantable ventricular assist devices as destination therapy will increase. Surgeons will be able to select several options of the treatment for CHF by understanding the advantages and disadvantages of those surgical treatments.

Human adults automatically mimic others' emotional expressions, which is believed to contribute to sharing emotions with others. Although this behaviour appears fundamental to social reciprocity, little is known about its developmental process. Therefore, we examined whether infants show automatic facial mimicry in response to others' emotional expressions. Facial electromyographic activity over the corrugator supercilii (brow) and zygomaticus major (cheek) of four- to five-month-old infants was measured while they viewed dynamic clips presenting audiovisual, visual and auditory emotions. The audiovisual bimodal emotion stimuli were a display of a laughing/crying facial expression with an emotionally congruent vocalization, whereas the visual/auditory unimodal emotion stimuli displayed those emotional faces/vocalizations paired with a neutral vocalization/face, respectively. Increased activation of the corrugator supercilii muscle in response to audiovisual cries and the zygomaticus major in response to audiovisual laughter were observed between 500 and 1000 ms after stimulus onset, which clearly suggests rapid facial mimicry. By contrast, both visual and auditory unimodal emotion stimuli did not activate the infants' corresponding muscles. These results revealed that automatic facial mimicry is present as early as five months of age, when multimodal emotional information is present., (© 2016 The Author(s).)

The tricuspid regurgitation (TR) is so-called 'functional' rather than organic. And therefore, it was originally thought that in most patients with secondary TR, surgical treatment of the left side heart valve would correct the problems of the TR. However, in recent study, the residual or recurrent TR showed poor prognosis after the surgery and the tricuspid valve is called 'forgotten' valve. The anatomy and pathophysiology of the tricuspid valve are shown as three-dimensional structure which is different from the "saddle-shaped" mitral annulus, and the finding suggests that an annuloplasty for TR is different from that for mitral regurgitation. The indication of tricuspid annuloplasty (TAP) for TR is not only the degree of TR but also annular dilatation without TR at the time of surgery. Tricuspid annuloplasty shows better long-term results after surgery than replacement and additional procedure may be required to prevent recurrence of TR after TAP. In this review, indication, the therapeutic procedures and prognosis depend on surgical procedure with or without ring or additional procedures are reviewed.