Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice.

The regulatory network of genes and molecules in sleep/wakefulness remains to be elucidated. Here we describe the methodology and workflow of the dominant screening of randomly mutagenized mice and discuss theoretical basis of forward genetics research for sleep in mice. Our high-throughput screening employs electroencephalogram (EEG) and electromyogram (EMG) to stage vigilance states into a wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS). Based on their near-identical sleep/wake behavior, C57BL/6J (B6J) and C57BL/6N (B6N) are chosen as mutagenized and counter strains, respectively. The total time spent in the wake and NREMS, as well as the REMS episode duration, shows sufficient reproducibility with small coefficients of variance, indicating that these parameters are most suitable for quantitative phenotype-driven screening. Coarse linkage analysis of the quantitative trait, combined with whole-exome sequencing, can identify the gene mutation associated with sleep abnormality. Our simulations calculate the achievable LOD score as a function of the phenotype strength and the numbers of mice examined. A pedigree showing a mild decrease in total wake time resulting from a heterozygous point mutation in the Cacna1a gene is described as an example.

Modelling state-transition dynamics in resting-state brain signals by the hidden Markov and Gaussian mixture models.

Recent studies have proposed that one can summarize brain activity into dynamics among a relatively small number of hidden states and that such an approach is a promising tool for revealing brain function. Hidden Markov models (HMMs) are a prevalent approach to inferring such neural dynamics among discrete brain states. However, the impact of assuming Markovian structure in neural time series data has not been sufficiently examined. Here, to address this situation and examine the performance of the HMM, we compare the model with the Gaussian mixture model (GMM), which is with no temporal regularization and thus a statistically simpler model than the HMM, by applying both models to synthetic time series generated from empirical resting-state functional magnetic resonance imaging (fMRI) data. We compared the GMM and HMM for various sampling frequencies, lengths of recording per participant, numbers of participants and numbers of independent component signals. We find that the HMM attains a better accuracy of estimating the hidden state than the GMM in a majority of cases. However, we also find that the accuracy of the GMM is comparable to that of the HMM under the condition that the sampling frequency is reasonably low (e.g., TR = 2.88 or 3.60 s) or the data are relatively short. These results suggest that the GMM can be a viable alternative to the HMM for investigating hidden-state dynamics under this condition.

Bridging the Micro-Macro Gap between Single-Molecular Behavior and Bulk Hydrolysis Properties of Cellulase.

The microscopic kinetics of enzymes at the single-molecule level often deviate considerably from those expected from bulk biochemical experiments. Here, we propose a coarse-grained-model approach to bridge this gap, focusing on the unexpectedly slow bulk hydrolysis of crystalline cellulose by cellulase, which constitutes a major obstacle to mass production of biofuels and biochemicals. Building on our previous success in tracking the movements of single molecules of cellulase on crystalline cellulose, we develop a mathematical description of the collective motion and function of enzyme molecules hydrolyzing the surface of cellulose. Model simulations robustly explained the experimental findings at both the microscopic and macroscopic levels and revealed a hitherto-unknown mechanism causing a considerable slowdown of the reaction, which we call the crowding-out effect. The size of the cellulase molecule impacted significantly on the collective dynamics, whereas the rate of molecular motion on the surface did not.

Age-related changes in the ease of dynamical transitions in human brain activity.

Executive functions, a set of cognitive processes that enable flexible behavioral control, are known to decay with aging. Because such complex mental functions are considered to rely on the dynamic coordination of functionally different neural systems, the age-related decline in executive functions should be underpinned by alteration of large-scale neural dynamics. However, the effects of age on brain dynamics have not been firmly formulated. Here, we investigate such age-related changes in brain dynamics by applying "energy landscape analysis" to publicly available functional magnetic resonance imaging data from healthy younger and older human adults. We quantified the ease of dynamical transitions between different major patterns of brain activity, and estimated it for the default mode network (DMN) and the cingulo-opercular network (CON) separately. We found that the two age groups shared qualitatively the same trajectories of brain dynamics in both the DMN and CON. However, in both of networks, the ease of transitions was significantly smaller in the older than the younger group. Moreover, the ease of transitions was associated with the performance in executive function tasks in a doubly dissociated manner: for the younger adults, the ability of executive functions was mainly correlated with the ease of transitions in the CON, whereas that for the older adults was specifically associated with the ease of transitions in the DMN. These results provide direct biological evidence for age-related changes in macroscopic brain dynamics and suggest that such neural dynamics play key roles when individuals carry out cognitively demanding tasks.

Reinforcement Learning Explains Conditional Cooperation and Its Moody Cousin.

Direct reciprocity, or repeated interaction, is a main mechanism to sustain cooperation under social dilemmas involving two individuals. For larger groups and networks, which are probably more relevant to understanding and engineering our society, experiments employing repeated multiplayer social dilemma games have suggested that humans often show conditional cooperation behavior and its moody variant. Mechanisms underlying these behaviors largely remain unclear. Here we provide a proximate account for this behavior by showing that individuals adopting a type of reinforcement learning, called aspiration learning, phenomenologically behave as conditional cooperator. By definition, individuals are satisfied if and only if the obtained payoff is larger than a fixed aspiration level. They reinforce actions that have resulted in satisfactory outcomes and anti-reinforce those yielding unsatisfactory outcomes. The results obtained in the present study are general in that they explain extant experimental results obtained for both so-called moody and non-moody conditional cooperation, prisoner's dilemma and public goods games, and well-mixed groups and networks. Different from the previous theory, individuals are assumed to have no access to information about what other individuals are doing such that they cannot explicitly use conditional cooperation rules. In this sense, myopic aspiration learning in which the unconditional propensity of cooperation is modulated in every discrete time step explains conditional behavior of humans. Aspiration learners showing (moody) conditional cooperation obeyed a noisy GRIM-like strategy. This is different from the Pavlov, a reinforcement learning strategy promoting mutual cooperation in two-player situations.

Functional coupling between auditory memory and verbal transformations.

The ability to parse sound mixtures into coherent auditory objects is fundamental to cognitive functions, such as speech comprehension and language acquisition. Yet, we still lack a clear understanding of how auditory objects are formed. To address this question, we studied a speech-specific case of perceptual multistability, called verbal transformations (VTs), in which a variety of verbal forms is induced by continuous repetition of a physically unchanging word. Here, we investigated the degree to which auditory memory through sensory adaptation influences VTs. Specifically, we hypothesized that when memory persistence is longer, participants are able to retain the current verbal form longer, resulting in sensory adaptation, which in turn, affects auditory perception. Participants performed VT and auditory memory tasks on different days. In the VT task, Japanese participants continuously reported their perception while listening to a Japanese word (2- or 3-mora in length) played repeatedly for 5 min. In the auditory memory task, a different sequence of three morae, e.g., /ka/, /hi/, and /su/, was presented to each ear simultaneously. After some period (0-4 s), participants were visually cued to recall one of the sequences, i.e., in the left or right ear. We found that delayed recall accuracy was negatively correlated with the number of VTs, particularly under 2-mora conditions. This suggests that memory persistence is important for formation and selection of perceptual objects.

Striatal GABA levels correlate with risk sensitivity in monetary loss.

Background: Decision-making under risk is a common challenge. It is known that risk-taking behavior varies between contexts of reward and punishment, yet the mechanisms underlying this asymmetry in risk sensitivity remain unclear. Methods: This study used a monetary task to investigate neurochemical mechanisms and brain dynamics underpinning risk sensitivity. Twenty-eight participants engaged in a task requiring selection of visual stimuli to maximize monetary gains and minimize monetary losses. We modeled participant trial-and-error processes using reinforcement learning. Results: Participants with higher subjective utility parameters showed risk preference in the gain domain (r = -0.59) and risk avoidance in the loss domain (r = -0.77). Magnetic resonance spectroscopy (MRS) revealed that risk avoidance in the loss domain was associated with γ-aminobutyric acid (GABA) levels in the ventral striatum (r = -0.42), but not in the insula (r = -0.15). Using functional magnetic resonance imaging (fMRI), we tested whether risk-sensitive brain dynamics contribute to participant risky choices. Energy landscape analyses demonstrated that higher switching rates between brain states, including the striatum and insula, were correlated with risk avoidance in the loss domain (r = -0.59), a relationship not observed in the gain domain (r = -0.02). Conclusions: These findings from MRS and fMRI suggest that distinct mechanisms are involved in gain/loss decision making, mediated by subcortical neurometabolite levels and brain dynamic transitions.

Quality of gastric cancer care in designated cancer care hospitals in Japan.

OBJECTIVE: To develop a set of process-of-care quality indicators (QIs) that would cover a wide range of gastric cancer care modalities and to examine the current state of the quality of care provided by designated cancer care hospitals in Japan. DESIGN: A retrospective medical record review. SETTING: Eighteen designated cancer care hospitals throughout Japan. PARTICIPANTS: A total of 1685 patients diagnosed with gastric cancer in 2007. MAIN OUTCOME MEASURES: Provision of care to eligible patients as described in the 29 QIs, which were developed using an adaptation of the RAND/UCLA (University of California, Los Angeles) appropriateness method by a panel of nationally recognized experts in Japan. RESULTS: Overall, the patients received 68.3% of the care processes recommended by the QIs. While 'deep venous thrombosis prophylaxis before major surgery' was performed for 99% of the cases, 'documentation before endoscopic resection' was completed for only 12% of the cases. The chemotherapy care was less likely to meet the QI standards (61%) than pre-therapeutic care (76%), surgical treatment (66%) and endoscopic resection (71%; overall difference: P < 0.001). A comparison based on the types of care showed that documentation and patient explanation were performed less frequently (60 and 53%, respectively) than were diagnostic and therapeutic processes as recommended in the QIs (85%; overall P < 0.001). CONCLUSIONS: Although many required care processes were provided, some areas with room for improvement were revealed, especially with respect to chemotherapy, documentation and patient explanation. Continuous efforts to improve the quality and develop a system to monitor this progress would be beneficial in Japan.

Pedunculated hamartomatous polyp of the appendix: report of a case.

We experienced a rare case of a pedunculated polyp of the appendix, which had been incidentally found by preventive appendectomy performed when providing surgical treatment for rectal carcinoma. A pathological investigation of this polypoid lesion demonstrated branches of fibro-muscular stalks connecting with the lamina muscularis covered by a hyperplastic mucosa, which proved to be consistent with the features of hamartoma. The patient had no external characteristics of Peutz-Jeghers syndrome, including mucocutaneous pigmentation and gastrointestinal polyposis, observed by endoscopy. This case is considered to be a Peutz-Jeghers type polyp of the appendix with a pedunculated form, which is very rare.

[Combined therapy of lapatinib and capecitabine effective against local recurrence of breast cancer].

A 67-year-old woman after mastectomy was afflicted with local recurrence of left breast cancer during adjuvant trastuzumab therapy. Oral administration of lapatinib and capecitabine served to distinguish the recurrent tumor and also reduce the patient's distressing symptoms. This combined anti-cancer therapy may be available for patients with breast cancer for whom trastuzumab therapy was not adequately effective.

Impact of high preoperative steroid doses on postoperative complications among patients on prolonged preoperative steroid therapy.

Corticosteroids are essential to maintain the organic homeostasis. Steroid, glucocorticoid or its synthetic analog is widely used for inflammatory and autoimmune diseases. Prolonged steroid therapy is reported to cause the susceptibility to infection, impaired wound healing and psychoneurosis, however whether the quantity of taking the preoperative steroid is associated the postoperative complication is still unknown. The aim of this study was to elucidate whether the steroid dose in patients on prolonged preoperative steroid therapy is associated postoperative morbidity and mortality. Twenty-five patients taking steroid for various illnesses and underwent the surgery under general anesthesia were selected in this study. The mean +/- standard deviation and the median of the steroid dose converted into hydrocortisone (mg/day) were 39.2 +/- 31.0 and 20, respectively. Of 25 cases, postoperative complications were seen in 10 cases. The postoperative complication was severe based on the grade of Clavien and Dindo by ANOVA as the doses of taking steroid increased (p = 0.0171). The grave postoperative complication classified as Clavien and Dindo grade III occurred with 100% sensitivity and 87% specificity for the steroid dose converted into hydrocortisone > 80 mg/day. Preoperative taking the large amount of steroid (> 80 mg/day) could cause a grave complication. More careful selection of the operative procedure might improve the mobidity rate.

Pathological Prognostic Score: a rational criteria to stratify survival in colorectal carcinoma.

PURPOSE: The aim of this study is to certify a rationality of Pathological Prognostic Score (PPS) in determining the prognosis of patients with colorectal carcinoma. METHODS: Three hundred and thirty-one patients with colorectal carcinoma, which had been treated by surgical resection, were enrolled. One point was added for each element among four tumor-related pathological factors of depth of tumor, lymph node metastasis, venous invasion, and lymphatic invasion. PPS was determined by an aggregate of the points. RESULTS: There existed a significant difference both between survivals of patients with PPS 0 or 1 and 2 or 3 (P = 0.0005) and between survivals of patients with PPS 2 or 3 and 4 (P < 0.0001). CONCLUSIONS: PPS could be an easy and useful criteria to stratify prognosis of patients with colorectal carcinoma.

Analysis of the impact of the body mass index in patients with gastric carcinoma.

BACKGROUND: Body mass index (BMI) has been suggested to provide clinicopathological information in tumor development and progression in patients with gastric carcinoma. METHODS: The correlation of BMI with clinicopathological features and operation-related factors was analyzed in 308 patients with gastric carcinoma who had undergone distal or total gastrectomy. RESULTS: There was no significant correlation of obesity, indicated by a high value of BMI, with tumor-related factors including survival, or with operation-related factors. On the other hand, more advanced tumors and worse preoperative nutritional and immunological conditions were found in patients with a lower value of BMI. CONCLUSIONS: BMI might be a representation of the physical condition brought about by the extent of tumor progression rather than a factor influencing the factors related to gastric carcinoma.

The prognostic nutritional index can be a prognostic indicator in colorectal carcinoma.

PURPOSE: Preoperative assessments regarding a patient's immunological and nutritional condition are required to predict the outcomes of patients with malignant tumors. The aim of the current study was to clarify the significance of Onodera's prognostic nutritional index (OPNI), which can simply account for the immunological and nutritional conditions, in patients with colorectal carcinoma. METHODS: The correlations of the preoperative OPNI value with clinicopathological features were examined in 219 patients with colorectal carcinoma who had been surgically treated. RESULTS: Not only the tumor stage (P = 0.028) and venous invasion (P = 0.002), but also an OPNI of less than 40 (P = 0.002) were found to be independently correlated with a worse prognosis of patients with colorectal carcinoma. CONCLUSION: The preoperative OPNI can be used as a simple prognostic indicator in colorectal carcinoma.

Dynamic Transitions Between Brain States Predict Auditory Attentional Fluctuations.

Achievement of task performance is required to maintain a constant level of attention. Attentional level fluctuates over the course of daily activities. However, brain dynamics leading to attentional fluctuation are still unknown. We investigated the underlying mechanisms of sustained attention using functional magnetic resonance imaging (fMRI). Participants were scanned with fMRI while performing an auditory, gradual-onset, continuous performance task (gradCPT). In this task, narrations gradually changed from one to the next. Participants pressed a button for frequent Go trials (i.e., male voices) as quickly as possible and withheld responses to infrequent No-go trials (i.e., female voices). Event-related analysis revealed that frontal and temporal areas, including the auditory cortex, were activated during successful and unsuccessful inhibition of predominant responses. Reaction-time (RT) variability throughout the auditory gradCPT was positively correlated with signal changes in regions of the dorsal attention network: superior frontal gyrus and superior parietal lobule. Energy landscape analysis showed that task-related activations could be clustered into different attractors: regions of the dorsal attention network and default mode network. The number of alternations between RT-stable and erratic periods increased with an increase in transitions between attractors in the brain. Therefore, we conclude that dynamic transitions between brain states are closely linked to auditory attentional fluctuations.

Preoperative elevation of serum C-reactive protein as an independent prognostic indicator for gastric cancer.

PURPOSE: Preoperative elevation of serum C-reactive protein (CRP) is a prognostic indicator for some malignant tumors. We investigated the clinicopathologic importance of an elevated preoperative serum CRP value in gastric carcinoma patients. METHODS: We studied the relationship between the preoperative serum CRP value and clinicopathologic characteristics in 204 patients who underwent curative resection of gastric carcinoma. RESULTS: The patients with preoperative CRP elevation had significantly poorer survival than those without CRP elevation (P < 0.0001). According to multivariate analysis, the factors independently associated with an unfavorable prognosis were a high preoperative CRP value (P = 0.024), lymphatic invasion (P = 0.017) and advanced tumor stage (P = 0.016). CONCLUSION: Preoperative serum CRP elevation can be an independent prognostic indicator in patients with gastric carcinoma.

Primary neuroendocrine carcinoma of the breast: report of a case.

Primary neuroendocrine carcinoma (NEC) of the breast appears to be a rare neoplasm. Due to the limited number of the cases, a definitive therapeutic option for the disease has not yet been established. We herein report the case of a 57-year-old female patient with primary NEC of the breast who underwent a surgical resection and for whom the suitable adjuvant therapy is now being considered.

Gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis.

Surgical palliation of malignant obstructive pancreatitis poses a considerable burden to patients, especially those with extensive disease. We herein present a novel technique for performing gastro-pancreaticostomy using a tube stent as a less invasive palliative treatment for malignant obstructive pancreatitis. The main pancreatic duct was punctured via the wall of the pyloric antrum. After the insertion of a guidewire, a double pigtail-type tube stent with side holes was inserted into the main pancreatic duct through the wall of the pyloric antrum. This technique was useful as a means of accomplishing less invasive palliative treatment, and has the potential to improve the quality of life for patients with malignant obstructive pancreatitis.

[Prominent efficacy from capecitabine mono-therapy for a case with lymphangiosis carcinomatosa derived from recurrent breast cancer].

We met a 61-year-old woman who had been suffering from dyspnea due to pleuritis carcinomatosa derived from recurrent breast cancer for which no former chemotherapy had been effective. Capecitabine mono-therapy could exert a drastic anticancer effect for lymphangiosis carcinomatosa causing more severe symptoms of dyspnea. This therapeutic option could be selected for patients with recurrent breast cancer for which the first- or second-line chemotherapy could not provide a sufficient anti-cancer efficacy and possibly serve to sustain the life quality of the patients.