EPG2S: Speech Generation and Speech Enhancement based on Electropalatography and Audio Signals using Multimodal Learning

Speech generation and enhancement based on articulatory movements facilitate communication when the scope of verbal communication is absent, e.g., in patients who have lost the ability to speak. Although various techniques have been proposed to this end, electropalatography (EPG), which is a monitoring technique that records contact between the tongue and hard palate during speech, has not been adequately explored. Herein, we propose a novel multimodal EPG-to-speech (EPG2S) system that utilizes EPG and speech signals for speech generation and enhancement. Different fusion strategies based on multiple combinations of EPG and noisy speech signals are examined, and the viability of the proposed method is investigated. Experimental results indicate that EPG2S achieves desirable speech generation outcomes based solely on EPG signals. Further, the addition of noisy speech signals is observed to improve quality and intelligibility. Additionally, EPG2S is observed to achieve high-quality speech enhancement based solely on audio signals, with the addition of EPG signals further improving the performance. The late fusion strategy is deemed to be the most effective approach for simultaneous speech generation and enhancement.Comment: Accepted By IEEE Signal Processing Lette

The epidemiology of gastrointestinal stromal tumors in Taiwan, 1998–2008: a nation-wide cancer registry-based study

BACKGROUND: To investigate the incidence of gastrointestinal stromal tumors (GISTs) in Taiwan and the impact of imatinib on the overall survival (OS) of GIST patients. METHODS: GISTs were identified from the Taiwan Cancer Registry (TCR) from 1998 to 2008. The age-adjusted incidence rates and the observed OS rates were calculated. Cox proportional hazards models were applied to examine the mortality risk in three time periods (1998–2001, 2002–2004, 2005–2008) according to the application and availability of imatinib. RESULTS: From 1998 to 2008, 2,986 GISTs were diagnosed in Taiwan. The incidence increased from 1.13 per 100,000 in 1998 to 1.97 per 100,000 in 2008. The most common sites were stomach (47-59%), small intestine (31-38%), and colon/rectum (6-9%). The 5-year observed OS was 66.5% (60.3% for men, 74.2% for women, P < .0001). GISTs in the stomach had a better 5-year observed OS (69.4%) than those in the small intestine (65.1%) (P < .0001). The outcome of GIST improved significantly after the more widespread use of imatinib; the 5-year observed OS increased from 58.9% during 1998–2001 to 70.2% during 2005–2008 (P < .0001). Younger age, female sex, stomach location, and later diagnostic years were independent predictors of a better survival. CONCLUSIONS: The incidence of GIST has been increasing in Taiwan, partially due to the advancement of diagnostic technology/method and the increased awareness by physicians. The outcome of GIST has improved significantly with the availability and the wider use of imatinib

Ontology-based Fuzzy Markup Language Agent for Student and Robot Co-Learning

An intelligent robot agent based on domain ontology, machine learning mechanism, and Fuzzy Markup Language (FML) for students and robot co-learning is presented in this paper. The machine-human co-learning model is established to help various students learn the mathematical concepts based on their learning ability and performance. Meanwhile, the robot acts as a teacher's assistant to co-learn with children in the class. The FML-based knowledge base and rule base are embedded in the robot so that the teachers can get feedback from the robot on whether students make progress or not. Next, we inferred students' learning performance based on learning content's difficulty and students' ability, concentration level, as well as teamwork sprit in the class. Experimental results show that learning with the robot is helpful for disadvantaged and below-basic children. Moreover, the accuracy of the intelligent FML-based agent for student learning is increased after machine learning mechanism.Comment: This paper is submitted to IEEE WCCI 2018 Conference for revie

Liposomal irinotecan and 5-fluorouracil/leucovorin in older patients with metastatic pancreatic cancer - A subgroup analysis of the pivotal NAPOLI-1 trial

Irinotecan liposomal; Pacients grans; Càncer de pàncreesIrinotecán liposomal; Pacientes mayores; Cáncer de páncreasLiposomal irinotecan; Older patients; Pancreatic cancerObjectives Pancreatic cancer is a highly lethal disease predominantly affecting older patients. Characterization of outcomes in these patients may help optimise treatment decisions. The global, phase 3 NAPOLI-1 trial ( NCT01494506 ) demonstrated an overall survival (OS) benefit with liposomal irinotecan and 5-flurouracil/leucovorin (nal-IRI + 5-FU/LV) versus 5-FU/LV. This subgroup analysis explored impact of age on outcomes in NAPOLI-1 patients, and nal-IRI + 5-FU/LV efficacy and safety in older patients. Materials and Methods This exploratory, post-hoc analysis of the NAPOLI-1 trial included patients aged ≥eighteen years (no upper limit) with metastatic pancreatic adenocarcinoma that had progressed on gemcitabine-based therapy. Patients were stratified by age (cut-offs at 65, 70, and 75 years); OS and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Results Of 417 randomized patients, 192 (46%), 110 (26%) and 43 (10%) were aged ≥65, ≥70 and ≥ 75 years, respectively. Mortality risk and risk of disease progression were similar in older and younger patients independent of treatment (HRs for median [m]OS/mPFS comparisons were 0.88/0.95 [ .25). Reduced mortality/morbidity risk with nal-IRI + 5-FU/LV in older subgroups was in line with the wider population. No additional toxicities with nal-IRI + 5-FU/LV were observed in older patients: 86% of patients ≥75 years versus 69% <75 years required a dose delay or reduction due to toxicities (43% versus 32% dose reductions). Discussion Results suggest that older patients with metastatic pancreatic adenocarcinoma that progressed on prior gemcitabine-based treatment can benefit from second-line therapy, supporting nal-IRI + 5-FU/LV treatment in older patients.The NAPOLI-1 trial (ClinicalTrials.govidentifier: NCT01494506) was sponsored by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA; Medical writing support was provided by Laura McMahon of Physicians World Europe GmbH, Mannheim, Germany, and funded by Shire International, Zug, Switzerland. Correction and publication costs were funded by Global Medical Affairs, Servier, Suresnes, France

E2F transcription factor 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinomas

AbstractNasopharyngeal carcinoma (NPC) is an endemic head and neck epithelial malignancy in Southeastern Asia and Taiwan. The E2 factor (E2F) family of transcription factors is downstream targets of the retinoblastoma protein 1. The E2F family of transcription factors is the key regulator of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. However, the expression of E2F1 protein and its clinicopathological associations in patients with NPC are yet to be evaluated. Immunoexpression of E2F1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcomes were correlated with clinicopathological features and patient survivals. Results indicated that high E2F1 protein level (50%) was correlated with primary tumor (p < 0.001) and stage (p = 0.002; 7th American Joint Committee on Cancer). In multivariate analyses, high E2F1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.003), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.039). In conclusion, high E2F1 protein level is common, associated with adverse prognosticators, and might confer tumor aggressiveness through tumor cell proliferation and metastasis

Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 105 and 1 × 106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors

BACKGROUND: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial. PATIENTS AND METHODS: Patients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) for the first 4 weeks of 6-week cycles. Baseline characteristics and efficacy in the overall population were compared with those in patients who survived ≥1 year. Through 16th November 2015, 382 overall survival events had occurred. RESULTS: The overall survival advantage for nal-IRI+5-FU/LV vs 5-FU/LV was maintained from the original nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) analysis (6.2 vs 4.2 months, respectively; HR, 0.75; 95% confidence interval: 0.57-0.99). Median progression-free survival, objective response rate and disease control rate also favoured nal-IRI+5-FU/LV therapy. Estimated one-year overall survival rates were 26% with nal-IRI+5-FU/LV and 16% with 5-FU/LV. Baseline characteristics associated with long-term survival in the nal-IRI+5-FU/LV arm were Karnofsky performance status ≥90, age ≤65 years, lower CA19-9 levels, neutrophil-to-lymphocyte ratio ≤5 and no liver metastases. No new safety concerns were detected. CONCLUSIONS: The survival benefits of nal-IRI+5-FU/LV versus 5-FU/LV were maintained over an extended follow-up, and prognostic markers of survival ≥1 year were identified. CLINICAL TRIAL REGISTRATION NUMBER: NCT01494506

Liposomal irinotecan in metastatic pancreatic adenocarcinoma in Asian patients: Subgroup analysis of the NAPOLI-1 study

The global, randomized NAPOLI-1 phase 3 trial reported a survival benefit with liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after previous gemcitabine-based therapy. Median overall survival (OS) with nal-IRI+5-FU/LV was 6.1 vs 4.2 months with 5-FU/LV alone (unstratified hazard ratio [HR] = 0.67, P =.012). Herein, we report efficacy and safety results from a post-hoc subgroup analysis of Asian patients treated at Asian centers. Primary study endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Patients receiving nal-IRI+5-FU/LV (n = 34) had significantly longer median OS versus 5-FU/LV (n = 35) (8.9 vs 3.7 months; unstratified HR = 0.51, P =.025). Patients had significantly increased median PFS with nal-IRI+5-FU/LV versus 5-FU/LV (4.0 vs 1.4; unstratified HR = 0.48, P =.011), and increased ORR (8.8% vs 0; P =.114). nal-IRI monotherapy (n = 50) numerically improved efficacy endpoints versus 5-FU/ LV (n = 48): median OS was 5.8 versus 4.3 months (HR = 0.83, P =.423) a nd m edian PFS was 2.8 versus 1.4 months (HR = 0.69, P =.155). Grade =3 neutropenia was reported more frequently with nal-IRI+5-FU/LV versus 5-FU/LV (54.5% vs 3.4%), and incidence of grade =3 diarrhea was comparable between the two arms (3.0% vs 6.9%). This subgroup analysis confirms nal-IRI+5-FU/LV as an efficacious treatment option that improves survival in Asian patients with mPDAC that progressed after gemcitabine-based therapy, with a safety profile agreeing with previous findings. The nal-IRI+5-FU/LV regimen should represent a new standard of care for these patients in Asia. (Clinicaltrials. gov: NCT01494506)