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Background Junctional epidermolysis bullosa is a rare skin and mucosal disorder characterized by blister formation in response to minor trauma and extracutaneous manifestations. There have been no reports of cardiac surgery and prognostication in patients with epidermolysis bullosa due to skin and mucosal fragility. Case presentation: A 55-year-old man presented with congenital junctional epidermolysis bullosa, hypertension, and vasospastic angina. He complained of dyspnea on exertion, and transthoracic echocardiography revealed severe aortic valve regurgitation, moderate aortic valve stenosis (tricuspid valve), and severe mitral valve regurgitation. Considering that the skin condition in the right chest wall was relatively healthy, the right thoracotomy approach was preferred and totally endoscopic concomitant mitral valve repair and aortic valve replacement were performed using a sutureless bioprosthetic valve (Perceval™ (Corcym, Group, Milan, Italy)). Polyurethane and silicon dressing foams were used to protect the skin at the site of contact with the bag valve mask, arterial pressure catheter, intravenous catheter, and the tracheal intubation tube. Vertical mattress sutures were used for the skin sutures. The postoperative course was uneventful, and the patient was discharged nine days after the operation. There was no indication for reoperation until three years follow-up period. Conclusions The totally endoscopic concomitant aortic and mitral valve surgery using Perceval™ prosthesis can be performed safely in patients with junctional epidermolysis bullosa by adequate protection of the skin and mucosa.

Prolongation is a speech disfluency that lengthens some portions of speech utterances. It is frequently observed in children's spontaneous speech, while it is rare in read speech. To make acoustic models more robust to children's spontaneous speech, collecting a large amount of children's speech data containing prolongation is usually required, which is very impractical in many cases. To tackle this problem, we propose a novel data augmentation method that virtually generates additional data by simulating prolongation. The method inserts pseudo frames into specific positions of speech utterances to simulate prolongation. The acoustic features of the inserted frames are calculated from the original frames on both sides. This is based on our analysis that many of vowels are actually stretched in children's spontaneous speech. Our proposed procedure can generate partially stretched utterances with low computational costs, unlike a conventional speed or tempo perturbation method that extends and shrinks entire utterances at a uniform rate. The effectiveness of the proposed method were confirmed with the experiments of acoustic model adaptations, in which our proposed method focusing on vowel stretch showed consistent improvement compared with conventional speed and tempo perturbation approach.

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.

Although neural language models have emerged, n-gram language models are still used for many speech recognition tasks. This paper proposes four methods to improve n-gram language models using text generated from a recurrent neural network language model (RNNLM). First, we use multiple RNNLMs from different domains instead of a single RNNLM. The final n-gram language model is obtained by interpolating generated n-gram models from each domain. Second, we use subwords instead of words for RNNLM to reduce the out-of-vocabulary rate. Third, we generate text templates using an RNNLM for template-based data augmentation for named entities. Fourth, we use both forward RNNLM and backward RNNLM to generate text. We found that these four methods improved performance of speech recognition up to 4% relative in various tasks.

Praziquantel is widely used for treating parasitic infections globally, especially in countries with endemic schistosomiasis. However, severe hypersensitivity to praziquantel has rarely been reported. We report the case of a 30-year-old Japanese man who developed acute generalized exanthematous pustulosis (AGEP), which is a rare and severe cutaneous reaction usually triggered by drugs, after taking praziquantel. During medical examination, eggs of Diphyllobothrium nihonkaiense were found in his stool. He took praziquantel 600 mg for 1 day and developed skin rashes and fever the next day. Pruritic generalized maculopapular erythematous eruptions were observed over the entire body. He had elevated white blood cell count, liver enzymes, and C-reactive protein level. We prescribed acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and topical ointments including difluprednate and hydrocortisone. Over the next 3 days, he developed pinhead-sized, non-follicular pustules on his diffusely erythematous skin. Histological findings of the pustular lesion showed spongiform subcorneal pustules with perivascular inflammatory cells. Approximately 8 days after taking praziquantel, the pustules resolved with desquamation. He became afebrile on day 9 and his laboratory parameters returned to normal levels on day 16. He was diagnosed with AGEP caused by praziquantel. Physicians need to be aware that praziquantel could cause AGEP, although it is generally considered a safe drug.

Background: A prior phase I/IIa clinical trial provided evidence for safety, feasibility and potential efficacy of i.m. injection of granulocyte colony-stimulating factor (G-CSF)-mobilized CD34+ cells in patients with critical limb ischemia (CLI). Methods and Results: A phase II trial of CD34+ cell therapy was conducted in patients with CLI to explore endpoint selection and timing. No-option CLI patients (n=11) underwent i.m. transplantation of G-CSF-mobilized CD34+ cells isolated by magnetic sorting. Ischemic rest pain scales improved from week 2 vs. baseline (P

Background Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and potentially effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome of the cell therapy has yet to be reported. Methods and results Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with Buerger's disease died by week 208 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and 104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant improvement of toe brachial pressure index versus baseline was sustained up to week 208 and that of transcutaneous partial oxygen pressure was kept up to week 156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance significantly improved at week 52, the final evaluation time point, compared with baseline. Subgroup analysis revealed the similar outcome in patients with Buerger's disease. Conclusions Favorable clinical outcomes as well as physiological evidences strongly indicate the long-term benefit of GCSF-mobilized CD34+ cell transplantation for retrieval from CLI, especially in patients with Buerger's disease.

Background The majority of patients with cholinergic urticaria presents with strong hypersensitivity to autologous sweat. Patients with severe cholinergic urticaria are frequently resistant to H1 antagonists which are used in conventional therapies for various types of urticaria. It has been reported that desensitization using partially purified sweat antigen was effective in a patient with cholinergic urticaria. Methods The aim of this study is to determine the usefulness of rapid desensitization with autologous sweat in severe cholinergic urticaria, because rapid desensitization has proven to be a quick and effective immunotherapy for allergies to various allergens. Six patients with severe cholinergic urticaria who are resistant to H1 antagonists and have sweat hypersensitivity were enrolled in a rapid desensitization protocol. Results In all six patients, the responses for skin tests with autologous sweat were attenuated after rapid desensitization with autologous sweat. Two of the three cholinergic urticaria patients showed reduced histamine release with autologous sweat after the rapid desensitization with autologous sweat. Further, the rapid desensitization and subsequent maintenance treatment reduced the symptoms in five of the six patients. Conclusions This study provides evidence that rapid desensitization with autologous sweat is beneficial for treating cholinergic urticaria patients resistant to conventional therapy who have sweat hypersensitivity.

We present herein a Japanese case of Rosai-Dorfman disease (RDD) in which cutaneous manifestations completely remitted after treatment with low-dose oral corticosteroid. A 69-year-old Japanese man presented with a 1-year history of enlarged submandibular lymph nodes and subsequent nasal and pharyngeal bleeding. RDD was diagnosed based on biopsy results from a lymph node in the left parotid region. The patient had also noted several skin eruptions that repeatedly appeared and disappeared on the face and arms. Biopsies were taken from skin eruptions on the face and cuboidal fossa. Both biopsy specimens showed dense, well-demarcated infiltration of histiocytes, lymphocytes and multinucleated giant cells from just under the epidermis to the subcutaneous tissue. These histiocytes were positive for CD68 and S-100, but negative for CD1a, and some displayed emperipolesis. Given the histopathological findings and the fact that the patient was suffering from RDD, skin lesions were diagnosed as cutaneous manifestations of RDD. Cutaneous lesions gradually began to persist concomitant with enlargement of extranodal lymphadenopathy in the nasopharyngeal area. Increasing respiratory obstruction prompted a trial with oral prednisolone commencing at 0.4 mg/kg per day. Both the lymphadenopathy and skin lesions responded quickly. Within 3 months, all his skin lesions disappeared completely with almost complete resolution of lymphadenopathy. Twelve months after the beginning of oral prednisolone therapy, slight recurrence of mucosal and cutaneous lesions appeared, but disappeared quickly with an increase in prednisolone to 0.3 mg/kg per day. Low-dose prednisolone appeared very effective in the case of RDD.

Automatic prosody labeling is the task of automatically annotating prosodic labels such as syllable stresses or break indices into speech corpora. Prosody-labeled corpora are important for speech synthesis and automatic speech understanding. However, the subtleness of physical features makes accurate labeling difficult. Since errors in the prosodic labels can lead to incorrect prosody estimation and unnatural synthetic sound, the accuracy of the labels is a key factor for text-to-speech (TTS) systems. In particular, mora accent labels relevant to pitch are very important for Japanese, since Japanese is a pitch-accent language and Japanese people have a particularly keen sense of pitch accents. However, the determination of the mora accents of Japanese is a more difficult task than English stress detection in a way. This is because the context of words changes the mora accents within the word, which is different from English stress where the stress is normally put at the lexical primary stress of a word. In this paper, we propose a method that can accurately determine the prosodic labels of Japanese using both acoustic and linguistic models. A speaker-independent linguistic model provides mora-level knowledge about the possible correct accentuations in Japanese, and contributes to reduction of the required size of the speaker-dependent speech corpus for training the other stochastic models. Our experiments show the effectiveness of the combination of models.

68歳男性。2003年5月中旬より右腎部に腫瘤を自覚し, 右鼠径部にリンパ節が腫脹してきたので2003年6月23日当科を受診した。初診時3.4×3.7cm大で弾性硬の紅褐色皮下腫瘤を呈し, 生検にてメルケル細胞癌と診断した。2003年7月30日広範囲切除, 右鼠径・外腸骨リンパ節郭清術を施行し, 右鼠径部リンパ節転移を認めたため, 術後放射線療法を追加した。その後再発転移なく経過したが, 2005年4月血清NSE値が上昇し, CT上で多発肝転移像を認めた。エトポシド・シスプラチン療法は効果なく, シクロフォスファミド・ドキソルビシン・ビンクリスチン療法が著効し, 一旦CRとなった。しかし, 10月に肝転移が再発し, 胸腔内転移も認め, アムルビシンを投与するも効果なく, 2005年12月永眠された。多発肝転移を来した症例で, 化学療法の選択に難渋した。

This paper describes the application of IBM TAKMI® for Biomedical Documents to facilitate knowledge discovery from the very large text databases characteristic of life science and healthcare applications. This set of tools, designated MedTAKMI, is an extension of the TAKMI (Text Analysis and Knowledge MIning) system originally developed for text mining in customer-relationship-management applications. MedTAKMI dynamically and interactively mines a collection of documents to obtain characteristic features within them. By using multifaceted mining of these documents together with biomedically motivated categories for term extraction and a series of drill-down queries, users can obtain knowledge about a specific topic after seeing only a few key documents. In addition, the use of natural language techniques makes it possible to extract deeper relationships among biomedical concepts. The MedTAKMI system is capable of mining the entire MEDLINE® database of 11 million biomedical journal abstracts. It is currently running at a customer site.

Large text databases potentially contain a great wealth of knowledge. However, text represents factual information (and information about the author's communicative intentions) in a complex, rich, and opaque manner. Consequently, unlike numerical and fixed field data, it cannot be analyzed by standard statistical data mining methods. Relying on human analysis results in either huge workloads or the analysis of only a tiny fraction of the database. We are working on text mining technology to extract knowledge from very large amounts of textual data. Unlike information retrieval technology that allows a user to select documents that meet the user's requirements and interests, or document clustering technology that organizes documents, we focus on finding valuable patterns and rules in text that indicate trends and significant features about specific topics. By applying our prototype system named TAKMI (Text Analysis and Knowledge Mining) to textual databases in PC help centers, we can automatically detect product failures; determine issues that have led to rapid increases in the number of calls and their underlying reasons; and analyze help center productivity and changes in customers' behavior involving a particular product, without reading any of the text. We have verified that our framework is also effective for other data such as patent documents.

Depletion of the ozone layer has been observed on a global scale. Ozone depletion increases the amount of biologically harmful solar ultraviolet radiation (UV) that reaches the surface of the Earth, leading to an increased incidence of skin cancer. We previously reported the prevalence and incidence of actinic keratosis (AK) in Kasai City, which is located almost at the center of Japan. To evaluate the effects of different ambient annual UV doses on the prevalence and incidence of non-melanoma skin cancer and AK in Japan, we screened for skin cancer on Ie Island in Okinawa at the southern end of Japan, where the annual cumulative dose of UV is assumed to be the highest in Japan. The island had a population of 5562 in 1993. A prospective 4-year population-based study on the prevalence and incidence of cutaneous neoplasms was conducted by examining the sun-exposed skin of people over 40 years of age living on Ie Island. In 1993–1996, 86 cases of AK, nine of basal cell carcinoma (BCC), and two of squamous cell carcinoma were identified. The annual prevalence of AK on Ie Island was 1159.4 in 1993, 572.8 in 1994, 1014.3 in 1995 and 988.9 per 100 000 Japanese in 1996. These values were significantly higher than those in Kasai City. The annual age-adjusted odds ratios for AK of Ie Island to Kasai City were 2.79, 1.38, 2.45 and 2.39, respectively. The incidences of AK on Ie Island per 100 000 were 637.0 in 1995 and 625.5 in 1996, which were also significantly higher than those in Kasai City (223.6 in 1993 and 171.2 in 1994). The prevalence of BCC was 123.6 and the incidence was 26.1. Together with our previous reports, the present results show a possible inverse relationship between the prevalence and incidence of AK and latitude among Japanese people.

An autonomous robot “Khepera” was simulated with a sensory-motor model, which evolves in the genetic algorithm (GA) framework, with the fitness evaluation in terms of the navigation performance in a maze course. The sensory-motor model is a developed neural network decoded from a graph-represented chromosome, which is evolved in the GA process with several genetic operators. It was found that the fitness landscape is very rugged when it is observed at the starting point of the course. A hypothesis for this ruggedness is proposed, and is supported by the measurement of fractal dimension. It is also observed that the performance is sometimes plagued by “Loss of Robustness,” after the robot makes major evolutionary jumps. Here, the robustness is quantitatively defined as a ratio of the averaged fitness of the evolved robot navigating in perturbed environments over the fitness of the evolved robot in the referenced environment. Possible explanation of robustness loss is the over-adaptation occurred in the environment where the evolution was taken place. Testing some other possibilities for this loss of robustness, many simulation experiments were conducted which smooth out the discrete factors in the model and environment. It was found that smoothing the discrete factors does not solve the loss of robustness. An effective method for maintaining the robustness is the use of averaged fitness over different navigation conditions. The evolved models in the simulated environment were tested by down-loading the models into the real Khepera robot. It is demonstrated that the tendency of fitness values observed in the simulation were adequately regenerated.

Most of the epidemiological studies on skin cancer that have been conducted to date have addressed the incidence in light-skinned Caucasians. To determine the prevalence rate of skin cancer and actinic keratosis (AK) on sun-exposed body sites of Japanese in Japan, we examined the skin of 4736 people during health examinations. The study was undertaken in Kasai City, Japan, which had a population of 52837 in 1992, where participants in a regional health examination were seen by dermatologists. The final diagnosis was made histopathologically. Participants were also interviewed by means of a questionnaire. A total of 36 cases of AK and two of basal cell carcinoma were identified, to give a prevalence of 413.4 per 100 000 for AK. The prevalence among outdoor workers was significantly higher than that of indoor workers. Furthermore, when the participants were classified into three Japanese skin types, the prevalence of AK among people of skin Type I, who are sensitive to UV irradiation, was significantly higher than that among people of skin Types II and III, who are less sensitive.

Variations in the Glutathione S-transferase (GST) supergene family have been reported to influence cancer susceptibility in Caucasian. However the genetic backgrounds and skin types are quite different between Caucasian and non-Caucasian. We therefore investigated the distribution of GST gene polymorphism in a Japanese population to ascertain the role of this polymorphism in melanomagenesis. Forty-six patients with cutaneous malignant melanoma and 92 healthy individuals who visited Kobe University Hospital between April 2004 and November 2010 were enrolled in this study. Genotype of GST gene was determined by using polymerase chain reaction-restriction fragments length polymorphism analysis. The frequencies of GSTM1 null genotype were significantly different between malignant melanoma and controls (adjusted odds ratio=2.25, 95% confidence interval 1.06-4.77). The polymorphism of GSTM1 locus could be associated with cutaneous malignant melanoma risk among Japanese population.

p53, A tumor suppressor gene, has been documented as the most frequently mutated gene in human cancers including non-melanoma skin tumors. It has been controversial whether the p53 gene mutation plays a major role for melanoma genesis. To examine the role of p53 in human malignant melanoma carcinogenesis, we performed immunohistochemical analysis using anti-p53 antibodies (CM-1 and DO-7) in microwaved paraffin sections. When cases having more than 1% reactive cells were regarded as positive, immunohistochemical analysis revealed that in primary melanomas 14 of 51 (27%) were positive with CM-1 or 15 of 51 (29%) were positive with DO-7. Tumor thickness of primary melanomas in p53 positive cases was significantly thicker than that in p53 negative cases. In metastatic melanomas, 35 of 41 (85%) lymph node metastases were positive with either antibody and in skin metastases 16 of 28 (57%) lesions with CM-1 or 18 of 28 (64%) lesions with DO-7 were positive. The mean percentages of reactive cells were 2.3% in primary lesions and 4.9% in metastases. The incidence of positivity was significantly higher in metastases than primary lesions. In 10 cases examined, with both primary and metastatic melanoma, 3 cases were negative in both lesions and 1 case was positive in both lesions, while 6 cases were negative in the primary lesions and positive only in metastatic lesions. Four Spitz nevi, 6 dysplastic nevi and 11 common nevi were all negative. These data suggest that the expression of p53 protein may be a late event in melanoma progression.

Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV-induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 +/- 1.3 tumors per mouse, and control mice had 6.3 +/- 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome-treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV-induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal-looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome-treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.