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A 16-year-old male with no previous medical history developed sudden fever and urinary dysfunction. He was admitted to our hospital due to bilateral leg weakness and sensory disturbance on the third day of weakness onset. A sagittal T 2 -weighted image displayed a longitudinal extensive lesion of transverse myelitis in the spinal column from the upper cervical (C2) to the thoracic region (Th9). The patient was diagnosed with autoimmune myelitis and treated with four courses of intravenous methylprednisolone (1 g/day for three consecutive days per week). This improved his signs, and his serum sample tested negative for anti-aquaporin-4 (AQP-4) antibody but positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody in cell-based assays. We report this case of longitudinally extensive transverse myelitis involving fifteen vertebral bodies positive for anti-MOG antibody.

Thalidomide is a teratogen that causes multiple malformations in the developing baby through its interaction with cereblon (CRBN), a substrate receptor subunit of the CRL4 E3 ubiquitin ligase complex. CRBN was originally reported as a gene associated with autosomal recessive non-syndromic mild mental retardation. However, the function of CRBN during brain development remains largely unknown. Here we demonstrate that CRBN promotes brain development by facilitating the proliferation of neural stem cells (NSCs). Knockdown of CRBN in zebrafish embryos impaired brain development and led to small brains, as did treatment with thalidomide. By contrast, overexpression of CRBN resulted in enlarged brains, leading to the expansion of NSC regions and increased cell proliferation in the early brain field and an expanded expression of brain region-specific genes and neural and glial marker genes. These results demonstrate that CRBN functions in the determination of brain size by regulating the proliferation of NSCs during development., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

A 71-year-old male with no previous medical history was admitted to our hospital for paralysis of the right upper extremity. Although DWI of the brain revealed high-intensity signals in the bilateral frontal and left parietal lobes, CT revealed a hyperdense spot in the anterior superior sagittal sinus (SSS). Because CT venography revealed SSS occlusion, he was diagnosed with cerebral venous thrombosis (CVT). In addition, laboratory findings, including free triiodothyronine, 8.85 pg/ml; thyroxine, 3.39 pg/dl, thyroid-stimulating hormone (TSH), < 0.02 μU/ml; and anti-TSH receptor antibody, 5.7 IU/l, led to the diagnosis of hyperthyroidism for the first time. Moreover, factor VIII procoagulant protein levels exhibited a marked increase (187.5%). Based on these findings, the patient was diagnosed with CVT due to Graves' disease.

The stochastic multicolor labeling method 'Brainbow' is a powerful strategy to label multiple neurons differentially with fluorescent proteins; however, the fluorescence levels provided by the original attempts to use this strategy were inadequate. In the present study, we developed a stochastic multicolor labeling method with enhanced expression levels that uses a tetracycline-operator system (Tetbow). We optimized Tetbow for either plasmid or virus vector-mediated multicolor labeling. When combined with tissue clearing, Tetbow was powerful enough to visualize the three-dimensional architecture of individual neurons. Using Tetbow, we were able to visualize the axonal projection patterns of individual mitral/tufted cells along several millimeters in the mouse olfactory system. We also developed a Tetbow system with chemical tags, in which genetically encoded chemical tags were labeled with synthetic fluorophores. This was useful in expanding the repertoire of the fluorescence labels and the applications of the Tetbow system. Together, these new tools facilitate light-microscopy-based neuronal tracing at both a large scale and a high resolution., Competing Interests: RS, ML, TI No competing interests declared, (© 2018, Sakaguchi et al.)

Tissue clearing techniques are useful for large-scale three-dimensional fluorescence imaging of thick tissues. However, high-resolution imaging deep inside tissues has been challenging, as it is extremely sensitive to light scattering and spherical aberrations. Here, we present a water-based optical clearing and mounting media, SeeDB2, which is designed for high numerical aperture (NA) objective lenses with oil or glycerol immersion. Using quick and simple soaking procedures, the refractive indices of samples can be matched either to that of immersion oil (1.52) or glycerol (1.46), thus minimizing light scattering and spherical aberrations. Fine morphology and various fluorescent proteins are highly preserved during the clearing and imaging process. Our method is useful for the three-dimensional fluorescence imaging of neuronal circuitry at synaptic resolution using confocal and super-resolution microscopy. SeeDB2 is also useful as a mounting media for the super-resolution imaging of fluorescent proteins., Competing Interests: Competing interestsM.-T.K. and T.I. have filed a patent application on SeeDB2, assigned to RIKEN., (Copyright © 2018 The Authors; exclusive licensee Bio-protocol LLC.)

A 63-year-old woman presented to our hospital with sudden symptoms of unsteadiness while walking. Based on the neurological findings, i.e., ataxia and absence of tendon reflex in the extremities accompanied by antecedent infection at the time, she was tentatively diagnosed with Fisher syndrome. Following intravenous immunoglobulin (IVIg) therapy for 5 days, her ataxic symptoms improved. Laboratory data were negative for antiganglioside antibody against GQ1b in the IgG subclass. Six months after her first admission, cognitive impairment gradually developed. She was re-admitted owing to new onset of unsteadiness while walking 1.5 years after her first admission. Diffusion-weighted brain MRI (DWI) revealed linear high-intensity signals in the region of the corticomedullary junction. Cutaneous skin biopsy revealed intranuclear inclusion bodies in sweat gland cells. Considering her family history along with the examination results, we diagnosed with adult-onset sporadic neuronal intranuclear inclusion disease (NIID). Retrospective investigation of the previous DWI obtained at the first admission had also shown slight linear high-intensity areas, suggesting that a series of events, including repeated sudden-onset transient ataxia, resulted due to NIID.

The aim of this study was to investigate the efficacy of a trunk stabilization exercise warm-up program in reducing the incidence of lower extremity injuries among male junior soccer players. Two junior soccer teams participated in this study. The intervention (INT) team performed three trunk stabilization exercises before practice sessions and games, while a control (CON) team performed their usual warm-up without trunk exercises. Both teams engaged in regular soccer training and games, and were followed for the incidence of injury. As a result, overall injury incidence rates (IRs) were 2.65 injuries/1,000 h and 4.94 injuries/1,000 h in the INT and CON teams, respectively (incidence rate ratio [IRR]=0.54, 95% confidence interval [CI]=0.32-0.89, p=0.013). The IR of acute injuries was significantly lower in the INT team (1.91 injuries/1,000 h) than in the CON team (4.06 injuries/1,000 h) (IRR=0.47, 95%CI=0.26-0.84, p=0.009). Regarding injury sites, the IRs of ankle injuries in the INT team (0.32 injuries/1,000 h) were significantly lower than that in the CON team (2.28 injuries/1,000 h) (IRR=0.14, 95%CI=0.04-0.47, p<0.001). These results suggest that a warm-up program comprising trunk stabilization exercises alone can prevent acute injuries, especially ankle injuries., Competing Interests: The authors declare no conflict of interest, (© Georg Thieme Verlag KG Stuttgart · New York.)

After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery., Competing Interests: The authors declare no conflicts of interest.

Mitral and tufted (M/T) cells in the olfactory bulb produce rich temporal patterns of activity in response to different odors. However, it remains unknown how these temporal patterns are generated and how they are utilized in olfaction. Here we show that temporal patterning effectively discriminates between the two sensory modalities detected by olfactory sensory neurons (OSNs): odor and airflow-driven mechanical signals. Sniff-induced mechanosensation generates glomerulus-specific oscillatory activity in M/T cells, whose phase was invariant across airflow speed. In contrast, odor stimulation caused phase shifts (phase coding). We also found that odor-evoked phase shifts are concentration invariant and stable across multiple sniff cycles, contrary to the labile nature of rate coding. The loss of oscillatory mechanosensation impaired the precision and stability of phase coding, demonstrating its role in olfaction. We propose that phase, not rate, coding is a robust encoding strategy of odor identity and is ensured by airflow-induced mechanosensation in OSNs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The low redox potential of selenide and selenol is physiologically important, as it confers efficient catalytic abilities to selenoproteins. Quantitative determination of selenol and selenide provide important clues for understanding the metabolism and physiological function of selenium. However, selective detection of selenol and selenide is extremely difficult because of their chemical similarity to thiol and sulfide. In this study, we established a highly sensitive, selective, quantitative, and simple method for detection of selenol and selenide, using a reaction with monochlorobimane (MCB), followed by ethyl acetate extraction of the product syn-(methyl,methyl)bimane. We analyzed selenide production from selenite, catalyzed by human glutathione reductase, and also determined selenide and selenol concentrations in Hepa1-6 cells using the MCB method, to demonstrate its practical applications. This study provides a new tool for selenium detection in biology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Phenotyping is an automated technique that can be used to distinguish patients based on electronic health records. To improve the quality of medical care and advance type 2 diabetes mellitus (T2DM) research, the demand for T2DM phenotyping has been increasing. Some existing phenotyping algorithms are not sufficiently accurate for screening or identifying clinical research subjects., Objective: We propose a practical phenotyping framework using both expert knowledge and a machine learning approach to develop 2 phenotyping algorithms: one is for screening; the other is for identifying research subjects., Methods: We employ expert knowledge as rules to exclude obvious control patients and machine learning to increase accuracy for complicated patients. We developed phenotyping algorithms on the basis of our framework and performed binary classification to determine whether a patient has T2DM. To facilitate development of practical phenotyping algorithms, this study introduces new evaluation metrics: area under the precision-sensitivity curve (AUPS) with a high sensitivity and AUPS with a high positive predictive value., Results: The proposed phenotyping algorithms based on our framework show higher performance than baseline algorithms. Our proposed framework can be used to develop 2 types of phenotyping algorithms depending on the tuning approach: one for screening, the other for identifying research subjects., Conclusions: We develop a novel phenotyping framework that can be easily implemented on the basis of proper evaluation metrics, which are in accordance with users' objectives. The phenotyping algorithms based on our framework are useful for extraction of T2DM patients in retrospective studies.

Background: Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems., Methods: We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases., Results: We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images., Conclusions: Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information from a variety of sources.

To estimate a diagnostic probability similarly to experts using answers to interviews, we developed a system that fundamentally behaves as a Bayesian model. For predefined interviews, we defined the sensitivity and specificity related to one or more diagnoses. Additionally, we used a predefined parent-child relation between diagnoses to decrease the number of parameters to set. After calculating the disease probability, we trained the model using the difference of post-test probability between computer calculations and three experts' opinions. We evaluated the effects of setting up tree structures. When using a tree structure, the model trained faster and produced better fitting results than the model without tree structure. Training with multiple raters' training data confused the model. The scores worsened in later epochs. Herein, we present the new method's benefits and characteristics.

Disease ontology, defined as a causal chain of abnormal states, is believed to be a valuable knowledge base in medical information systems. Automatic mapping between electronic health records (EHR) and disease ontology is indispensable for applying disease ontology in real clinical settings. Based on an analysis of ontologies of 148 chronic diseases, approximately 41% of abnormal states require information extraction from clinical narratives. This paper presents a semi-automatic framework to identify abnormal states in clinical narratives. This framework aims to effectively build mapping modules between EHR and disease ontology. We show that the proposed method is effective in data mapping for 18%-33% of the abnormal states in the ontologies of chronic diseases. Moreover, we analyze the abnormal states for which our method is invalid in extracting information from clinical narratives.

Phenotyping is an automated technique for identifying patients diagnosed with a particular disease based on electronic health records (EHRs). To evaluate phenotyping algorithms, which should be reproducible, the annotation of EHRs as a gold standard is critical. However, we have found that the different types of EHRs cannot be definitively annotated into CASEs or CONTROLs. The influence of such "possible patients" on phenotyping algorithms is unknown. To assess these issues, for four chronic diseases, we annotated EHRs by using information not directly referring to the diseases and developed two types of phenotyping algorithms for each disease. We confirmed that each disease included different types of possible patients. The performance of phenotyping algorithms differed depending on whether possible patients were considered as CASEs, and this was independent of the type of algorithms. Our results indicate that researchers must share annotation criteria for classifying the possible patients to reproduce phenotyping algorithms.

The glomerular map in the olfactory bulb (OB) is the basis for odor recognition. Once established during development, the glomerular map is stably maintained throughout the life of an animal despite the continuous turnover of olfactory sensory neurons (OSNs). However, traumatic damage to OSN axons in the adult often leads to dysosmia, a qualitative and quantitative change in olfaction in humans. A mouse model of dysosmia has previously indicated that there is an altered glomerular map in the OB after the OSN axon injury; however, the underlying mechanisms that cause the map distortion remain unknown. In this study, we examined how the glomerular map is disturbed and how the odor information processing in the OB is affected in the dysosmia model mice. We found that the anterior-posterior coarse targeting of OSN axons is disrupted after OSN axon injury, while the local axon sorting mechanisms remained. We also found that the connectivity of mitral/tufted cell dendrites is reduced after injury, leading to attenuated odor responses in mitral/tufted cells. These results suggest that existing OSN axons are an essential scaffold for maintaining the integrity of the olfactory circuit, both OSN axons and mitral/tufted cell dendrites, in the adult.

Background: Health level seven version 2.5 (HL7 v2.5) is a widespread messaging standard for information exchange between clinical information systems. By applying Semantic Web technologies for handling HL7 v2.5 messages, it is possible to integrate large-scale clinical data with life science knowledge resources., Objective: Showing feasibility of a querying method over large-scale resource description framework (RDF)-ized HL7 v2.5 messages using publicly available drug databases., Methods: We developed a method to convert HL7 v2.5 messages into the RDF. We also converted five kinds of drug databases into RDF and provided explicit links between the corresponding items among them. With those linked drug data, we then developed a method for query expansion to search the clinical data using semantic information on drug classes along with four types of temporal patterns. For evaluation purpose, medication orders and laboratory test results for a 3-year period at the University of Tokyo Hospital were used, and the query execution times were measured., Results: Approximately 650 million RDF triples for medication orders and 790 million RDF triples for laboratory test results were converted. Taking three types of query in use cases for detecting adverse events of drugs as an example, we confirmed these queries were represented in SPARQL Protocol and RDF Query Language (SPARQL) using our methods and comparison with conventional query expressions were performed. The measurement results confirm that the query time is feasible and increases logarithmically or linearly with the amount of data and without diverging., Conclusions: The proposed methods enabled query expressions that separate knowledge resources and clinical data, thereby suggesting the feasibility for improving the usability of clinical data by enhancing the knowledge resources. We also demonstrate that when HL7 v2.5 messages are automatically converted into RDF, searches are still possible through SPARQL without modifying the structure. As such, the proposed method benefits not only our hospitals, but also numerous hospitals that handle HL7 v2.5 messages. Our approach highlights a potential of large-scale data federation techniques to retrieve clinical information, which could be applied as applications of clinical intelligence to improve clinical practices, such as adverse drug event monitoring and cohort selection for a clinical study as well as discovering new knowledge from clinical information.

Super-resolution imaging deep inside tissues has been challenging, as it is extremely sensitive to light scattering and spherical aberrations. Here, we report an optimized optical clearing agent for high-resolution fluorescence imaging (SeeDB2). SeeDB2 matches the refractive indices of fixed tissues to that of immersion oil (1.518), thus minimizing both light scattering and spherical aberrations. During the clearing process, fine morphology and fluorescent proteins were highly preserved. SeeDB2 enabled super-resolution microscopy of various tissue samples up to a depth of >100 μm, an order of magnitude deeper than previously possible under standard mounting conditions. Using this approach, we demonstrate accumulation of inhibitory synapses on spine heads in NMDA-receptor-deficient neurons. In the fly medulla, we found unexpected heterogeneity in axon bouton orientations among Mi1 neurons, a part of the motion detection circuitry. Thus, volumetric super-resolution microscopy of cleared tissues is a powerful strategy in connectomic studies at synaptic levels., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Estrogens play central roles in sexual development, reproduction, and hepatocyte proliferation. The ovaries are one of the main organs for estradiol (E2) production. Ovariectomies (OVXs) were performed on the female mice, and hepatocyte proliferation was analyzed. The ovariectomized mice exhibited delayed hepatocyte proliferation after partial hepatectomy (PH) and also exhibited delayed and reduced E2 induction. Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα). The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH. Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle. Taken together, these findings indicate that E2 accelerated ERα expression in periportal hepatocytes and hepatocyte proliferation in the female mice.

Background: Matrix metalloproteinase-9 (MMP-9) plays a key role for the blood-brain barrier disruption and intravenous tissue plasminogen activator (iv-tPA) therapy increases MMP-9. Edaravone, a free radical scavenger, reduces MMP-9-related blood-brain barrier disruption. We aimed to investigate whether edaravone would suppress the MMP-9 increase after iv-tPA using low-dose alteplase (0.6 mg/kg)., Subjects: Patients hospitalized within 12 hours after ischemic stroke onset between April 2008 and June 2013 were retrospectively examined. Patients with slight deficits (National Institutes of Health Stroke Scale score ≤ 4), stroke caused by arterial dissection, severe inflammatory disease or autoimmune disease, or regular use of steroid were excluded. Serum concentrations of high-sensitivity C-reactive protein, interleukin-6, MMP-2, and MMP-9 were serially measured at admission, after 24 hours, day 7, and day 14. General linear models were used to compare changes in concentrations of these biomarkers over time., Results: A total of 63 patients (38 men, aged 74.48 ± 13.8 years) were studied. Patients were divided into 2 groups according to the iv-tPA therapy, that is, tPA group (n = 32) and non-tPA group (n = 31). Edaravone was administered routinely except for contraindication (90.6% in the tPA group and 87.1% in the non-tPA group). Significant interaction of group × time factor was observed only in MMP-9 concentrations by repeated-measure analysis of variance (P = .004). Association between iv-tPA therapy and subsequent hemorrhagic transformation was highly significant, but MMP-9 concentrations at any point did not predictive of subsequent hemorrhagic transformation (area under the receiver operating characteristic curve, .681)., Conclusions: Low-dose iv-tPA increases MMP-9 concentration even in combination with Edaravone. The effect of higher dosage of Edaravone on circulating MMP-9 concentration and subsequent hemorrhagic transformation should be investigated., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ∼1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. We aimed to determine the specific needs for telestroke networks and to estimate the effects on the number of thrombolytic therapies. Five of the 47 Japanese prefectures with various population densities to estimate the nationwide effect of telestroke networks were selected. The questionnaire survey was administered at hospitals in these prefectures that are authorized to admit patients with acute stroke. Low-volume hospitals that annually treated fewer than 12 patients with acute stroke had never used tissue plasminogen activator (tPA). The number of days when telestroke support might have been needed varied depending on the size of the population aged 65 years or older within a 30-minute-driving-time area of a hospital and the annual number of patients treated within 3 hours of onset. The geographic information system analysis showed that .6%-8.3% of the population lived in areas where they could not reach a hospital for acute stroke treatment within 60 minutes. If 24/7 full telestroke support was introduced to the existing hospitals, 6.8-69.3 more patients could be treated by intravenous (IV) tPA annually. These numbers exceeded the estimated annual increases of .8-13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving-time area. This study uncovered that many Japanese stroke hospitals, especially low-volume facilities located in rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support to these hospitals may be highly effective compared with the drip-and-ship network in an underserved area., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The over-65 population stands at 29 million, more than 20% of the total population in Japan. This is the highest rate in the world. One-person households and older couple households will be increasing. The aim of the present study was to identify whether life and family background are significant factors for delayed presentation to hospital after stroke onset. A total of 253 patients (mean age, 70.7 ± 13.2 years) with stroke was examined. Patients who presented to hospital within 3 hours of onset were categorized as the early presentation group, and the other patients were categorized as the late presentation group. Life and family background were classified into 3 categories, namely 1-person households, 2-person households, and patients living with 3 or more persons. Two-person households were further subdivided by the age of family members. Multivariate logistic regression analysis demonstrated that 1-person households (odds ratio [OR]: 2.980, 95% confidence interval [CI]: 1.108-8.011) and 2-person households with individuals 65 years and older (OR: 3.059, 95% CI: 1.297-7.217) were significant independent factors for delayed presentation, in addition to stroke subtype, time of stroke onset, and route of admission. Onset-to-door time in patients with night-time onset was significantly different among different types of households. Significant delay was demonstrated in 2-person households with 2 individuals 65 years and older compared with that in patients living with 3 or more persons (P = .038). Our findings show that delayed presentation to hospital is more likely in stroke patients living in an elderly couple household, especially those with evening onset in an aging society., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils--the olfactory glomeruli--that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.

This paper presents: (1) a framework of formal representation of ICD10, which functions as a bridge between ontological information and natural language expressions; and (2) a methodology to use formally described ICD10 for computer-assisted ICD coding. First, we analyzed and structurized the meanings of categories in 15 chapters of ICD10. Then we expanded the structured ICD10 (S-ICD10) by adding subordinate concepts and labels derived from Japanese Standard Disease Names. The information model to describe formal representation was refined repeatedly. The resultant model includes 74 types of semantic links. We also developed an ICD coding module based on S-ICD10 and a 'Coding Principle,' which achieved high accuracy (>70%) for four chapters. These results not only demonstrate the basic feasibility of our coding framework but might also inform the development of the information model for formal description framework in the ICD11 revision.

ICD-coding is a complex and difficult task. Coding results vary a great deal depending on each coder's ability. Although the Japanese Standard Disease-Code Master facilitates the coding tasks, it also engenders post-coordination problems derived from combinations of basic diseases (with ICD code) and modifiers. Post-coordination sometimes alters the original ICD code dramatically. To solve this problem, this paper presents a proposal for using internal structures of disease names to correct the ICD code. First, we built an internal structure analyzer, which achieved high (83.7%) accuracy. Results demonstrated that the analyzed output is helpful for precise ICD-coding tasks.

The International Classification of Diseases 10th version (ICD-10) is one of the standard and most important disease classifications. Since computerized ICD-10 coding systems have drawn a great deal of attention in the medical field, a great number of different coding systems have been proposed. This paper proposes a hybrid architecture of different coding systems. First, given an input disease name, three coding systems output codes with their confidence scores. A C4.5-based system selector then selects the best output by using both input statistics and the confidence score from each system. The experimental results demonstrated that the selector significantly boosts the overall performance (+3.4 points).

Radiology reports are written primarily in natural language. Automated extraction of malignant findings from narrative reports is an important technique for clinical support or alert generation for physicians. This paper proposes a method for automatically extracting malignant findings from narrative radiological reports written in Japanese. First, sentences are parsed and a medical attribute of each phrase is determined. Next, sub-trees related to radiological findings are extracted from a dependency tree using medical attributes. Finally, the malignant findings in each sub tree are extracted with their positive or negative assertions, each of which is determined by the multiplication of pos/neg signs along a path in a sub-tree. The recall and precision for the extraction of malignant findings with their positive or negative assertions were 76% and 91% respectively. The experimental results showed the validity of the proposed method for extracting malignant findings with correct assertions.

The peroxisome proliferator-activated receptor gamma (PPARgamma) mediates the activity of the insulin-sensitizing thiazolidinediones and plays an important role in adipocyte differentiation and fat accretion. The analysis of PPARgamma functions in mature adipocytes is precluded by lethality of PPARgamma(-/-) fetuses and tetraploid-rescued pups. Therefore we have selectively ablated PPARgamma in adipocytes of adult mice by using the tamoxifen-dependent Cre-ER(T2) recombination system. We show that mature PPARgamma-null white and brown adipocytes die within a few days and are replaced by newly formed PPARgamma-positive adipocytes, demonstrating that PPARgamma is essential for the in vivo survival of mature adipocytes, in addition to its well established requirement for their differentiation. Our data suggest that potent PPARgamma antagonists could be used to acutely reduce obesity.

This study is aimed at extracting diagnosis with positive or negative assertion from radiological report written in Japanese Natural Language. We get frequency of verb patterns that indicate pos/neg assertion, and extract a rule in order of the occurrence. We made customized dictionary of 36,152 terms relating to disease names or radiological findings, and tried to extract pairs of (pos/neg, disease and verb pattern ) by using rules according to the most frequent pattern from 1,524/5,000 CT reports (each report consists of 15.1 words on the average). We tried only a few rules so far, and continue to find other rules.