VoiceBank-2023: A Multi-Speaker Mandarin Speech Corpus for Constructing Personalized TTS Systems for the Speech Impaired

Services of personalized TTS systems for the Mandarin-speaking speech impaired are rarely mentioned. Taiwan started the VoiceBanking project in 2020, aiming to build a complete set of services to deliver personalized Mandarin TTS systems to amyotrophic lateral sclerosis patients. This paper reports the corpus design, corpus recording, data purging and correction for the corpus, and evaluations of the developed personalized TTS systems, for the VoiceBanking project. The developed corpus is named after the VoiceBank-2023 speech corpus because of its release year. The corpus contains 29.78 hours of utterances with prompts of short paragraphs and common phrases spoken by 111 native Mandarin speakers. The corpus is labeled with information about gender, degree of speech impairment, types of users, transcription, SNRs, and speaking rates. The VoiceBank-2023 is available by request for non-commercial use and welcomes all parties to join the VoiceBanking project to improve the services for the speech impaired.Comment: submitted to 26th International Conference of the ORIENTAL-COCOSD

High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis

IntroductionA negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients.MethodsWe included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level.ResultsAmong the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (−0.27, p = 0.004 and −0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: −0.27 [95%CI: −0.44, −0.10, p = 0.001]; −0.19 [95%CI: −0.37, −0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26–4.17], p = 0.006; 1.95 [95%CI: 1.08–3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers.DiscussionIn conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness

Stem Cell-Based Neuroprotective and Neurorestorative Strategies

Stem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs) derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells (iPS), reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases

ENU Mutagenesis Identifies Mice with Morbid Obesity and Severe Hyperinsulinemia Caused by a Novel Mutation in Leptin

BACKGROUND: Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. Leptin is central to the regulation of energy metabolism and control of body weight in mammals. METHODOLOGY/PRINCIPAL FINDINGS: To better recapitulate the complexity of human obesity syndrome, we applied N-ethyl-N-nitrosourea (ENU) mutagenesis in combination with a set of metabolic assays in screening mice for obesity. Mapping revealed linkage to the chromosome 6 within a region containing mouse Leptin gene. Sequencing on the candidate genes identified a novel T-to-A mutation in the third exon of Leptin gene, which translates to a V145E amino acid exchange in the leptin propeptide. Homozygous Leptin(145E/145E) mutant mice exhibited morbid obesity, accompanied by adipose hypertrophy, energy imbalance, and liver steatosis. This was further associated with severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperleptinemia, characteristics of human obesity syndrome. Hypothalamic leptin actions in inhibition of orexigenic peptides NPY and AgRP and induction of SOCS1 and SOCS3 were attenuated in Leptin(145E/145E) mice. Administration of exogenous wild-type leptin attenuated hyperphagia and body weight increase in Leptin(145E/145E) mice. However, mutant V145E leptin coimmunoprecipitated with leptin receptor, suggesting that the V145E mutation does not affect the binding of leptin to its receptor. Molecular modeling predicted that the mutated residue would form hydrogen bond with the adjacent residues, potentially affecting the structure and formation of an active complex with leptin receptor within that region. CONCLUSIONS/SIGNIFICANCE: Thus, our evolutionary, structural, and in vivo metabolic information suggests the residue 145 as of special function significance. The mouse model harboring leptin V145E mutation will provide new information on the current understanding of leptin biology and novel mouse model for the study of human obesity syndrome

Applying a Multiple Screening Program Aided by a Guideline-driven Computerized Decision Support System—A Pilot Experience in Yun-Lin, Taiwan

Although preventive tools decrease morbidity and mortality and promote health, these services are often underutilized. The purpose of this study was to create a workflow for an outpatient setting that incorporated a computerized decision support system to implement preventive recommendations as well as to evaluate its impacts on facilitating preventive care. Methods: Subjects visiting National Taiwan University Hospital Yun-Lin Branch were evaluated by a questionnaire, which contained items to trigger production rules to check the eligibility of screening for high coronary risk, diabetes mellitus, lipid disorder, hypertension, obesity, tobacco use, depression, colorectal cancer, breast cancer, cervical cancer, and osteoporosis. Patients were given health information about the diseases they were at risk for and the merits of preventive measures, scheduled for a clinic visit, and arranged to have access to screening tools. Physicians were prompted with clinical reminders on the encounter. The overall effectiveness of 11 components in this screening program was evaluated in terms of expected life saving. The cost-effectiveness ratio was represented in US dollars per life-year saved. Results: A total of 283 men and 199 women were identified to need one to six preventive interventions during a 2-month period. Preventive consultation was arranged and screening tools were performed. It was estimated that 412-1014 subjects would be needed to attend the program so as to save one life. The cost-effectiveness ratio ranged from US$30,000 to US$40,000 per life-year saved. Conclusion: A computer-aided screening program driven by the US Preventive Services Task Force recommendations has been successfully implemented in Yun-Lin, Taiwan, and provided useful information about local epidemiology and implications for future health policy making. [J Formos Med Assoc 2007; 106(1):58-68

Assessing the risk of clinical and pathologic factors for relapse of borderline ovarian tumours

The objective of this study was to identify clinical and pathologic factors that are significant to relapse in borderline ovarian tumours (BOT). All patients with BOTs from 1997 to 2012 in our institute were identified. 115 patients were included in the study. The Cox proportional hazards model was used to identify significant factors. The median age was 42 years (range 14–85 years). The majority of the patients were at FIGO stage I (88.7%), and most of the patients had mucinous histology (66.1%), reflecting the predominant distribution of mucinous BOTs in East Asia. The median follow-up was 3.3 years (range 0–4.1 years). Twelve patients (10.4%) relapsed and two died consequently. Advanced stage, invasive implants and restaging surgery were significant factors of recurrence. Serous tumours had slightly higher risk than mucinous tumours, but the difference was not significant. As the study was performed in an area where mucinous BOTs are predominant, the results may complement current literature on BOT management

Serum Intact Fibroblast Growth Factor 23 Levels Are Negatively Associated with Bone Mineral Density in Chronic Hemodialysis Patients

(1) Background: Fibroblast growth factor 23 (FGF23) is predominantly secreted from bone and plays an important role in mineral balance in chronic kidney disease. However, the relationship between FGF23 and bone mineral density (BMD) in chronic hemodialysis (CHD) patients remains unclear. (2) Methods: This was a cross-sectional observational study that involved 43 stable outpatients on CHD. A linear regression model was used to determine risk factors for BMD. Measurements included serum hemoglobin, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), sclerostin, Dickkopf-1, α-klotho, 1,25-hydroxyvitamin D, intact parathyroid hormone levels and dialysis profiles. (3) Results: Study participants had a mean age of 59.4 ± 12.3 years, and 65% were male. In the multivariable analysis, cFGF23 levels showed no significant associations with the BMD of the lumbar spine (p = 0.387) nor that of the femoral head (p = 0.430). However, iFGF23 levels showed a significant negative association with the BMD of the lumbar spine (p = 0.015) and that of the femoral neck (p = 0.037). (4) Conclusions: Among patients on CHD, higher serum iFGF23 levels, but not serum cFGF23 levels, were associated with lower BMD values of the lumbar spine and femoral neck. However, further research is required to validate our findings

Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis.

BACKGROUND: Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs) is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear. METHODS: This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores. RESULTS: Patients with high interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), and were more likely to have chronic kidney disease (CKD) and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002) was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001) was an independent predictor of GFS. CONCLUSIONS: Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules