Gas-Filled Phospholipid Nanoparticles Conjugated with Gadolinium Play a Role as a Potential Theragnostics for MR-Guided HIFU Ablation

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C5F12-phospholipid nanobubbles (PLNs) 30–100 nm in diameter. The biochemical and physical characterization of Gd-C5F12-PLNs were performed. Since Gd-C5F12-PLN-50 (Φ = 50 nm) and Gd-C5F12-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C5F12-PLNs was longer than 1.5 hrs. Gd-C5F12-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C5F12-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C5F12-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C5F12-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation

Convolution channel separation and frequency sub-bands aggregation for music genre classification

In music, short-term features such as pitch and tempo constitute long-term semantic features such as melody and narrative. A music genre classification (MGC) system should be able to analyze these features. In this research, we propose a novel framework that can extract and aggregate both short- and long-term features hierarchically. Our framework is based on ECAPA-TDNN, where all the layers that extract short-term features are affected by the layers that extract long-term features because of the back-propagation training. To prevent the distortion of short-term features, we devised the convolution channel separation technique that separates short-term features from long-term feature extraction paths. To extract more diverse features from our framework, we incorporated the frequency sub-bands aggregation method, which divides the input spectrogram along frequency bandwidths and processes each segment. We evaluated our framework using the Melon Playlist dataset which is a large-scale dataset containing 600 times more data than GTZAN which is a widely used dataset in MGC studies. As the result, our framework achieved 70.4% accuracy, which was improved by 16.9% compared to a conventional framework

One-Step Knowledge Distillation and Fine-Tuning in Using Large Pre-Trained Self-Supervised Learning Models for Speaker Verification

The application of speech self-supervised learning (SSL) models has achieved remarkable performance in speaker verification (SV). However, there is a computational cost hurdle in employing them, which makes development and deployment difficult. Several studies have simply compressed SSL models through knowledge distillation (KD) without considering the target task. Consequently, these methods could not extract SV-tailored features. This paper suggests One-Step Knowledge Distillation and Fine-Tuning (OS-KDFT), which incorporates KD and fine-tuning (FT). We optimize a student model for SV during KD training to avert the distillation of inappropriate information for the SV. OS-KDFT could downsize Wav2Vec 2.0 based ECAPA-TDNN size by approximately 76.2%, and reduce the SSL model's inference time by 79% while presenting an EER of 0.98%. The proposed OS-KDFT is validated across VoxCeleb1 and VoxCeleb2 datasets and W2V2 and HuBERT SSL models. Experiments are available on our GitHub

Integrated Parameter-Efficient Tuning for General-Purpose Audio Models

The advent of hyper-scale and general-purpose pre-trained models is shifting the paradigm of building task-specific models for target tasks. In the field of audio research, task-agnostic pre-trained models with high transferability and adaptability have achieved state-of-the-art performances through fine-tuning for downstream tasks. Nevertheless, re-training all the parameters of these massive models entails an enormous amount of time and cost, along with a huge carbon footprint. To overcome these limitations, the present study explores and applies efficient transfer learning methods in the audio domain. We also propose an integrated parameter-efficient tuning (IPET) framework by aggregating the embedding prompt (a prompt-based learning approach), and the adapter (an effective transfer learning method). We demonstrate the efficacy of the proposed framework using two backbone pre-trained audio models with different characteristics: the audio spectrogram transformer and wav2vec 2.0. The proposed IPET framework exhibits remarkable performance compared to fine-tuning method with fewer trainable parameters in four downstream tasks: sound event classification, music genre classification, keyword spotting, and speaker verification. Furthermore, the authors identify and analyze the shortcomings of the IPET framework, providing lessons and research directions for parameter efficient tuning in the audio domain.Comment: 5 pages, 3 figures, submit to ICASSP202

PAS: Partial Additive Speech Data Augmentation Method for Noise Robust Speaker Verification

Background noise reduces speech intelligibility and quality, making speaker verification (SV) in noisy environments a challenging task. To improve the noise robustness of SV systems, additive noise data augmentation method has been commonly used. In this paper, we propose a new additive noise method, partial additive speech (PAS), which aims to train SV systems to be less affected by noisy environments. The experimental results demonstrate that PAS outperforms traditional additive noise in terms of equal error rates (EER), with relative improvements of 4.64% and 5.01% observed in SE-ResNet34 and ECAPA-TDNN. We also show the effectiveness of proposed method by analyzing attention modules and visualizing speaker embeddings.Comment: 5 pages, 2 figures, 1 table, accepted to CKAIA2023 as a conference pape

Mutations at codons 178, 200-129, and 232 contributed to the inherited prion diseases in Korean patients

Background: Polymorphisms of the human prion protein gene (PRNP) contribute to the genetic determinants of Creutzfeldt-Jakob disease (CJD). Numerous polymorphisms in the promoter regions as well as the open reading frame of PRNP were investigated. Greater than 90% of Korean, Chinese, and Japanese carry the homozygote 129 MM codon. In Korea, polymorphisms have not been comprehensively studied, except codons 129 and 219 in PRNP among Korean CJD cases. Although polymorphisms at codons 129 and 219 play an important role in susceptibility to sporadic CJD, patients with other polymorphisms in PRNP exhibited critical distinctions of clinical symptoms. Methods: The genetic analyses of PRNP were carried out among probable CJD patients in comparison with the results from magnetic resonance imaging (MRI) and electroencephalogram (EEG). Results: The molecular analyses revealed that three mutations at codons D178N, E200K, and M232R in heterozygosity. Patients with the D178N and M232R mutations had a 129MM codon, whereas the patient with the E200K mutation showed 129MV heterozygosity. They all revealed strong 14-3-3 positive signals. The 67-year-old patient with the D178N-129M mutation showed progressive gait disturbance and dysarthria was in progress. The 58-year-old patient with the E200K mutation coupled to the 129MV codon had gait disturbance, dysarthria, agitation, and ataxic gait, and progressed rapidly to death 3 months from the first onset of symptoms. The 65-year-old patient with the M232R mutation showed rapidly progressive memory decline and gait disturbance, and died within 16 months after onset of symptoms. Conclusion: Despite differences in ethnicity, the clinical and pathological outcomes were similar to the respective mutations around the world, except absence of insomnia in D178N-129M subject.This research was funded by the Ministry for Health, Welfare and Family Affairs, Korea (grant number, 4800-4835-301-210).Shiga Y, 2007, J NEUROL, V254, P1509, DOI 10.1007/s00415-007-0540-9Kovacs GG, 2005, HUM GENET, V118, P166, DOI 10.1007/s00439-005-0020-1Zarranz JJ, 2005, J NEUROL NEUROSUR PS, V76, P1491, DOI 10.1136/jnnp.2005.056606KONG Q, 2004, PRION BIOL DIS, P673Spacey SD, 2004, ARCH NEUROL-CHICAGO, V61, P122Huang N, 2003, NEUROLOGY, V61, P354Kovacs GG, 2002, J NEUROL, V249, P1567, DOI 10.1007/s00415-002-0896-9Collinge J, 2001, ANNU REV NEUROSCI, V24, P519Schroter A, 2000, ARCH NEUROL-CHICAGO, V57, P1751Wong NKC, 2000, J MOL GRAPH MODEL, V18, P126Taniwaki Y, 2000, J NEUROL NEUROSUR PS, V68, P388Wiltfang J, 1999, J NEUROCHEM, V73, P2485Hainfellner JA, 1999, ANN NEUROL, V45, P812Swietnicki W, 1998, J BIOL CHEM, V273, P31048Riek R, 1998, P NATL ACAD SCI USA, V95, P11667, DOI 10.1073/pnas.95.20.11667Zerr I, 1998, ANN NEUROL, V43, P32ZEIDLER M, 1998, WHO MANUAL STRENGTHERosenmann H, 1997, NEUROLOGY, V49, P593Hoque MZ, 1996, ACTA NEUROPATHOL, V92, P441Nagayama M, 1996, NEUROLOGY, V47, P1313Steinhoff BJ, 1996, ARCH NEUROL-CHICAGO, V53, P162PARCHI P, 1995, CURR OPIN NEUROL, V8, P286BROWN P, 1994, ANN NEUROL, V35, P513PRUSINER SB, 1994, ANN NEUROL, V35, P385GABIZON R, 1994, PHILOS T ROY SOC B, V343, P385HITOSHI S, 1993, J NEUROL SCI, V120, P208GOLDFARB LG, 1992, SCIENCE, V258, P806BROWN P, 1991, EUR J EPIDEMIOL, V7, P469STAHL N, 1990, BIOCHEMISTRY-US, V29, P8879BROWN P, 1986, ANN NEUROL, V20, P597

Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation

Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative pi-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C-H arylation. The functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Here the authors show a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts

Antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes mellitus

Hyperglycemia in the diabetic state increases oxidative stress and antioxidant therapy can be strongly correlated with decreased risks for diabetic complications. The purpose of this study is to determine antioxidant effect of garlic and aged black garlic in animal model of type 2 diabetes. The antioxidant activity of garlic and aged black garlic was measured as the activity in scavenging free radicals by the trolox equivalent antioxidant capacity (TEAC) assay. Three week-old db/db mice were fed AIN-93G diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Hepatic levels of lipid peroxides and activities of antioxidant enzymes were measured. TEAC values of garlic and aged black garlic were 13.3 ± 0.5 and 59.2 ± 0.8 µmol/g wet weight, respectively. Consumption of aged black garlic significantly decreased hepatic thiobarbituric acid reactive substances (TBARS) level compared with the garlic group which showed lower TBARS level than control group (p<0.05). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of garlic and aged black garlic group were significantly elevated compared to the control group. Catalase (CAT) activity of aged black garlic group was increased compared with the control group. These results show that aged black garlic exerts stronger antioxidant activity than garlic in vitro and in vivo, suggesting garlic and aged black garlic, to a greater extent, could be useful in preventing diabetic complications

Clear Cell "Sugar" Tumor of the Lung: A Well-Enhanced Mass with an Early Washout Pattern on Dynamic Contrast-Enhanced Computed Tomography

Clear cell tumor of the lung is a rare and very unusual benign pulmonary tumor. As clear cell tumor of the lung contains abundant cytoplasmic glycogen, this tumor is called "sugar tumor". We report a case of sugar tumor in a 64-yr-old man presenting as a round pulmonary nodule. On dynamic computed tomography (CT) scans, the solitary pulmonary nodule showed early wash-in enhancement with an early washout pattern like a lung malignancy. The patient underwent wedge resection for the tumor. Pathologic examination, including immunohistochemical studies, revealed that the nodule was a benign clear cell tumor, so-called "sugar tumor". Because only a small number of cases have been reported previously, clinical aspects, radiological characteristics on dynamic contrast-enhanced CT, and differential diagnosis of the tumor are not well established. Herein we present a clear cell tumor of the lung and discuss the clinical, radiological, and pathological features of the tumor

Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine