VISinger 2: High-Fidelity End-to-End Singing Voice Synthesis Enhanced by Digital Signal Processing Synthesizer

End-to-end singing voice synthesis (SVS) model VISinger can achieve better performance than the typical two-stage model with fewer parameters. However, VISinger has several problems: text-to-phase problem, the end-to-end model learns the meaningless mapping of text-to-phase; glitches problem, the harmonic components corresponding to the periodic signal of the voiced segment occurs a sudden change with audible artefacts; low sampling rate, the sampling rate of 24KHz does not meet the application needs of high-fidelity generation with the full-band rate (44.1KHz or higher). In this paper, we propose VISinger 2 to address these issues by integrating the digital signal processing (DSP) methods with VISinger. Specifically, inspired by recent advances in differentiable digital signal processing (DDSP), we incorporate a DSP synthesizer into the decoder to solve the above issues. The DSP synthesizer consists of a harmonic synthesizer and a noise synthesizer to generate periodic and aperiodic signals, respectively, from the latent representation z in VISinger. It supervises the posterior encoder to extract the latent representation without phase information and avoid the prior encoder modelling text-to-phase mapping. To avoid glitch artefacts, the HiFi-GAN is modified to accept the waveforms generated by the DSP synthesizer as a condition to produce the singing voice. Moreover, with the improved waveform decoder, VISinger 2 manages to generate 44.1kHz singing audio with richer expression and better quality. Experiments on OpenCpop corpus show that VISinger 2 outperforms VISinger, CpopSing and RefineSinger in both subjective and objective metrics.Comment: Submitted to ICASSP 202

Dynamic three-dimensional liver volume assessment of liver regeneration in hilar cholangiocarcinoma patients undergoing hemi-hepatectomy

BackgroundFor patients with hilar cholangiocarcinoma (HC) undergoing hemi-hepatectomy, there are controversies regarding the requirement of, indications for, and timing of preoperative biliary drainage (PBD). Dynamic three-dimensional volume reconstruction could effectively evaluate the regeneration of liver after surgery, which may provide assistance for exploring indications for PBD and optimal preoperative bilirubin value. The purpose of this study was to explore the indications for PBD and the optimal preoperative bilirubin value to improve prognosis for HC patients undergoing hemi-hepatectomy.MethodsWe retrospectively analyzed the data of HC patients who underwent hemi-hepatectomy in the First Affiliated Hospital of China Medical University from 2012 to 2023. The liver regeneration rate was calculated using three-dimensional volume reconstruction. We analyzed the factors affecting the liver regeneration rate and occurrence of postoperative liver insufficiency.ResultsThis study involved 83 patients with HC, which were divided into PBD group (n=36) and non-PBD group (n=47). The preoperative bilirubin level may be an independent risk factor affecting the liver regeneration rate (P=0.014) and postoperative liver insufficiency (P=0.016, odds ratio=1.016, β=0.016, 95% CI=1.003–1.029). For patients whose initial bilirubin level was >200 μmol/L (n=45), PBD resulted in better liver regeneration in the early stage (P=0.006) and reduced the incidence of postoperative liver insufficiency [P=0.012, odds ratio=0.144, 95% confidence interval (CI)=0.031–0.657]. The cut-off value of bilirubin was 103.15 μmol/L based on the liver regeneration rate. Patients with a preoperative bilirubin level of ≤103.15 μmol/L shown a better liver regeneration (P<0.01) and lower incidence of postoperative hepatic insufficiency (P=0.011, odds ratio=0.067, 95% CI=0.008–0.537).ConclusionFor HC patients undergoing hemi-hepatectomy whose initial bilirubin level is >200 μmol/L, PBD may result in better liver regeneration and reduce the incidence of postoperative liver insufficiency. Preoperative bilirubin levels ≤103.15 μmol/L maybe recommended for leading to a better liver regeneration and lower incidence of postoperative hepatic insufficiency

Factors influencing the level of insight and treatment attitude: a cross-sectional study of 141 elderly patients of major depression in Guangzhou, China

ObjectiveTo explore the insight, treatment attitude, and related influencing factors of hospitalized elderly patients suffering from major depression.MethodsA total of 141 hospitalized elderly patients with depression were selected as the research objects. Insight was evaluated by the total score of the Insight and Treatment Attitude questionnaire (ITAQ). The data collected included sociodemographic characteristics, psychiatric symptoms, delirium status, social functioning, social support, suicide risk, and cognitive function.ResultsThe sample included 74.5% of female patients, and the mean age was 67.53 (sd=7.19) years. The influencing factors of inpatients with depression included alcohol consumption, length of hospitalization, admission types, and the main caregivers (P<0.05). The various factors were further analyzed by linear regression, revealing that the insight and treatment attitude of elderly depressed hospitalized patients were mainly related to the Mini-Mental State Examination (MMSE) (β= 0.225, 95% CI 0.055–0.395, P=0.01), dependent on a caregiver (β=-5.810, 95% CI -8.086~-3.535, P<0.001), the type of admission (involuntary admission) (β=-3.365, 95% CI -5.448~-1.283, P=0.002), Functional Activities Questionnaire (FAQ) (β=-0.156, 95% CI -0.303~-0.010, P=0.037), and length of stay (≤28 days) (β=2.272, 95% CI 0.055~-4.489, P=0.045).ConclusionThe level of insight was affected by cognitive function, involuntary admission, dependent on a caregiver, social function and length of stay. Future studies should focus on cognitive function recovery, observation of admission mode, and self-care ability in elderly patients with depression

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci

Overt Cleft Palate Phenotype and TBX1 Genotype Correlations in Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome Patients

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000 – 1/4,000 live births. Approximately 9–11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, we hypothesized that DNA variants in the remaining allele of TBX1 may confer risk to CP in patients with 22q11DS. To test the hypothesis, we evaluated TBX1 exon sequencing (n = 360) and genotyping data (n = 737) with respect to presence (n = 54) or absence (n = 683) of CP in patients with 22q11DS. Two upstream SNPs (rs4819835 and rs5748410) showed individual evidence for association but they were not significant after correction for multiple testing. Associations were not identified between DNA variants and haplotypes in 22q11DS patients with CP. Overall, this study indicates that common DNA variants in TBX1 may be nominally causative for CP in patients with 22q11DS. This raises the possibility that genes elsewhere on the remaining allele of 22q11.2 or in the genome could be relevant

Genotype and Cardiovascular Phenotype Correlations With TBX1 in 1,022 Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients

Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial /DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2 could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP (single nucleotide polymorphism) number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype-enrichment groups. Nine common SNPs (minor allele frequency, MAF \u3e 0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome