Generative De-Quantization for Neural Speech Codec via Latent Diffusion

In low-bitrate speech coding, end-to-end speech coding networks aim to learn compact yet expressive features and a powerful decoder in a single network. A challenging problem as such results in unwelcome complexity increase and inferior speech quality. In this paper, we propose to separate the representation learning and information reconstruction tasks. We leverage an end-to-end codec for learning low-dimensional discrete tokens and employ a latent diffusion model to de-quantize coded features into a high-dimensional continuous space, relieving the decoder's burden of de-quantizing and upsampling. To mitigate the issue of over-smooth generation, we introduce midway-infilling with less noise reduction and stronger conditioning. In ablation studies, we investigate the hyperparameters for midway-infilling and latent diffusion space with different dimensions. Subjective listening tests show that our model outperforms the state-of-the-art at two low bitrates, 1.5 and 3 kbps. Codes and samples of this work are available on our webpage.Comment: Submitted to ICASSP 202

Native Multi-Band Audio Coding within Hyper-Autoencoded Reconstruction Propagation Networks

Spectral sub-bands do not portray the same perceptual relevance. In audio coding, it is therefore desirable to have independent control over each of the constituent bands so that bitrate assignment and signal reconstruction can be achieved efficiently. In this work, we present a novel neural audio coding network that natively supports a multi-band coding paradigm. Our model extends the idea of compressed skip connections in the U-Net-based codec, allowing for independent control over both core and high band-specific reconstructions and bit allocation. Our system reconstructs the full-band signal mainly from the condensed core-band code, therefore exploiting and showcasing its bandwidth extension capabilities to its fullest. Meanwhile, the low-bitrate high-band code helps the high-band reconstruction similarly to MPEG audio codecs' spectral bandwidth replication. MUSHRA tests show that the proposed model not only improves the quality of the core band by explicitly assigning more bits to it but retains a good quality in the high-band as well.Comment: Accepted to ICASSP 2023. For resources and examples, see https://saige.sice.indiana.edu/research-projects/HARP-Net

Hyperintense Thyroid Incidentaloma on Time of Flight Magnetic Resonance Angiography

Background: The purpose of this study was to evaluate the clinical significance of thyroid incidentaloma with hypersignal intensity on the time of flight magnetic resonance (TOF-MR) angiography and correlation with ultrasound (US).Methods: We retrospectively reviewed 3,505 non-contrast TOF-MR angiography performed at our institution between September 2014 and May 2017. Two radiologists correlated the thyroid incidentalomas detected on TOF-MR angiography with US features that were obtained within a three-month interval between MR and US examinations in consensus.Results: The prevalence of hyperintense thyroid nodules incidentally detected by TOF-MR angiography was 1.2% (43/3,505 patients). Among these, 35 people (77.8%) underwent US examinations, and a total of 45 hyperintense thyroid nodules were detected by US studies. Of these 45 nodules, more than 70% were categorized as benign on US exams. Fine needle aspiration was performed on nine nodules according to indications recommended by the Korean Society of Thyroid Radiology. All except one high-suspicion thyroid nodule were confirmed as benign (Bethesda 2) on cytologic examination. The high-suspicion nodule on US showed a nondiagnostic result (Bethesda 1). However, this nodule collapsed after aspiration of thick colloid.Conclusions: Our study demonstrated that the most hyperintense thyroid nodules detected on TOF-MR angiography were benign. Therefore, if a hyperintense incidentaloma is found on TOF-MR angiography, the thyroid nodule is more likely to be benign. We believe that these findings could offer additional information for further clinical management

Integrative molecular roadmap for direct conversion of fibroblasts into myocytes and myogenic progenitor cells

Transient MyoD overexpression in concert with small molecule treatment reprograms mouse fibroblasts into induced myogenic progenitor cells (iMPCs). However, the molecular landscape and mechanisms orchestrating this cellular conversion remain unknown. Here, we undertook an integrative multiomics approach to delineate the process of iMPC reprogramming in comparison to myogenic transdifferentiation mediated solely by MyoD. Using transcriptomics, proteomics, and genome-wide chromatin accessibility assays, we unravel distinct molecular trajectories that govern the two processes. Notably, only iMPC reprogramming is characterized by gradual up-regulation of muscle stem cell markers, unique signaling pathways, and chromatin remodelers in conjunction with exclusive chromatin opening in core myogenic promoters. In addition, we determine that the Notch pathway is indispensable for iMPC formation and self-renewal and further use the Notch ligand Dll1 to homogeneously propagate iMPCs. Collectively, this study charts divergent molecular blueprints for myogenic transdifferentiation or reprogramming and underpins the heightened capacity of iMPCs for capturing myogenesis ex vivo

CRISPR/Cas9 editing of directly reprogrammed myogenic progenitors restores dystrophin expression in a mouse model of muscular dystrophy

Genetic mutations in dystrophin manifest in Duchenne muscular dystrophy (DMD), the most commonly inherited muscle disease. Here, we report on reprogramming of fibroblasts from two DMD mouse models into induced myogenic progenitor cells (iMPCs) by MyoD overexpression in concert with small molecule treatment. DMD iMPCs proliferate extensively, while expressing myogenic stem cell markers including Pax7 and Myf5. Additionally, DMD iMPCs readily give rise to multinucleated myofibers that express mature skeletal muscle markers; however, they lack DYSTROPHIN expression. Utilizing an exon skipping-based approach with CRISPR/Cas9, we report on genetic correction of the dystrophin mutation in DMD iMPCs and restoration of protein expression in vitro. Furthermore, engraftment of corrected DMD iMPCs into the muscles of dystrophic mice restored DYSTROPHIN expression and contributed to the muscle stem cell reservoir. Collectively, our findings report on a novel in vitro cellular model for DMD and utilize it in conjunction with gene editing to restore DYSTROPHIN expression in vivo

Potential Association of DCBLD2 Polymorphisms with Fall Rates of FEV1 by Aspirin Provocation in Korean Asthmatics

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV1) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV1 decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV1-related phenotypes in asthmatics

Exclusive generation of rat spermatozoa in sterile mice utilizing blastocyst complementation with pluripotent stem cells

Blastocyst complementation denotes a technique that aims to generate organs, tissues, or cell types in animal chimeras via injection of pluripotent stem cells (PSCs) into genetically compromised blastocyst-stage embryos. Here, we report on successful complementation of the male germline in adult chimeras following injection of mouse or rat PSCs into mouse blastocysts carrying a mutation in Tsc22d3, an essential gene for spermatozoa production. Injection of mouse PSCs into Tsc22d3-Knockout (KO) blastocysts gave rise to intraspecies chimeras exclusively embodying PSC-derived functional spermatozoa. In addition, injection of rat embryonic stem cells (rESCs) into Tsc22d3-KO embryos produced interspecies mouse-rat chimeras solely harboring rat spermatids and spermatozoa capable of fertilizing oocytes. Furthermore, using single-cell RNA sequencing, we deconstructed rat spermatogenesis occurring in a mouse-rat chimera testis. Collectively, this study details a method for exclusive xenogeneic germ cell production in vivo, with implications that may extend to rat transgenesis, or endangered animal species conservation efforts. Keywords: Blastocyst complementation; artificial reproductive technology; germ cell production; interspecies chimerism; pluripotency; sterility