Deep Learning Models for Predicting Hearing Thresholds Based on Swept-Tone Stimulus-Frequency Otoacoustic Emissions.

OBJECTIVES: This study aims to develop deep learning (DL) models for the quantitative prediction of hearing thresholds based on stimulus-frequency otoacoustic emissions (SFOAEs) evoked by swept tones. DESIGN: A total of 174 ears with normal hearing and 388 ears with sensorineural hearing loss were studied. SFOAEs in the 0.3 to 4.3 kHz frequency range were recorded using linearly swept tones at a rate of 2 Hz/msec, with stimulus level changing from 40 to 60 dB SPL in 10 dB steps. Four DL models were used to predict hearing thresholds at octave frequencies from 0.5 to 4 kHz. The models-a conventional convolutional neural network (CNN), a hybrid CNN-k-nearest neighbor (KNN), a hybrid CNN-support vector machine (SVM), and a hybrid CNN-random forest (RF)-were individually built for each frequency. The input to the DL models was the measured raw SFOAE amplitude spectra and their corresponding signal to noise ratio spectra. All DL models shared a CNN-based feature self-extractor. They differed in that the conventional CNN utilized a fully connected layer to make the final regression decision, whereas the hybrid CNN-KNN, CNN-SVM, and CNN-RF models were designed by replacing the last fully connected layer of CNN model with a traditional machine learning (ML) regressor, that is, KNN, SVM, and RF, respectively. The model performance was evaluated using mean absolute error and SE averaged over 20 repetitions of 5 × 5 fold nested cross-validation. The performance of the proposed DL models was compared with two types of traditional ML models. RESULTS: The proposed SFOAE-based DL models resulted in an optimal mean absolute error of 5.98, 5.22, 5.51, and 6.06 dB at 0.5, 1, 2, and 4 kHz, respectively, superior to that obtained by the traditional ML models. The produced SEs were 8.55, 7.27, 7.58, and 7.95 dB at 0.5, 1, 2, and 4 kHz, respectively. All the DL models outperformed any of the traditional ML models. CONCLUSIONS: The proposed swept-tone SFOAE-based DL models were capable of quantitatively predicting hearing thresholds with satisfactory performance. With DL techniques, the underlying relationship between SFOAEs and hearing thresholds at disparate frequencies was explored and captured, potentially improving the diagnostic value of SFOAEs.

Context-dependent Plasticity and Strength of Subcortical Encoding of Musical Sounds Independently Underlie Pitch Discrimination for Music Melodies.

Subcortical auditory nuclei contribute to pitch perception, but how subcortical sound encoding is related to pitch processing for music perception remains unclear. Conventionally, enhanced subcortical sound encoding is considered underlying superior pitch discrimination. However, associations between superior auditory perception and the context-dependent plasticity of subcortical sound encoding are also documented. Here, we explored the subcortical neural correlates to music pitch perception by analyzing frequency-following responses (FFRs) to musical sounds presented in a predictable context and a random context. We found that the FFR inter-trial phase-locking (ITPL) was negatively correlated with behavioral performances of discrimination of pitches in music melodies. It was also negatively correlated with the plasticity indices measuring the variability of FFRs to physically identical sounds between the two contexts. The plasticity indices were consistently positively correlated with pitch discrimination performances, suggesting the subcortical context-dependent plasticity underlying music pitch perception. Moreover, the raw FFR spectral strength was not significantly correlated with pitch discrimination performances. However, it was positively correlated with behavioral performances when the FFR ITPL was controlled by partial correlations, suggesting that the strength of subcortical sound encoding underlies music pitch perception. When the spectral strength was controlled by partial correlations, the negative ITPL-behavioral correlations were maintained. Furthermore, the FFR ITPL, the plasticity indices, and the FFR spectral strength were more correlated with pitch than with rhythm discrimination performances. These findings suggest that the context-dependent plasticity and the strength of subcortical encoding of musical sounds are independently and perhaps specifically associated with pitch perception for music melodies.

Effects of Eucommia ulmoides extract against renal injury caused by long-term high purine diets in rats.

Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-ß1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-ß1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.

[Expression characteristics of inflammatory and apoptosis factors and regulatory effect of anemoside B4 in mice with acute kidney injury].

This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1ß(IL-1ß), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1ß, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.

[Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats].

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Cumulative risk assessment of phthalates in edible vegetable oil consumed by Chinese residents.

BACKGROUND: Phthalates have been widely used as plasticizers in various industries and are widely focused on in the international community as a result of their reproductive toxicity. Exposure of Chinese residents to phthalates via edible vegetable oil occurs often. In the present study, gas chromatography-mass spectrometry was used to detect the two main phthalates bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) in four major edible vegetable oil sources: an edible oil blend, soybean oil, peanut oil and rapeseed oil (a total of 1016 samples), as collected throughout China. Furthermore, cumulative risk assessment was used to estimate the reproductive health risk to Chinese residents caused by the phthalates that come from edible vegetable oils. RESULTS: Both phthalates were detected in four major edible vegetable oil sources. The phthalate with the highest detection rate was DBP (13.48%), followed by DEHP (7.78%). The results of the cumulative risk assessment showed that the hazard indices of these two phthalates in edible vegetable oils were less than 1, except in soybean oil. Nevertheless, the two phthalates had the lowest detection rates in soybean oil, which were 1.94% (DEHP) and 5.16% (DBP). In China, contamination levels of phthalates in the soils where oil crops are cultivated have a great influence on the phthalate concentrations in edible vegetable oils. CONCLUSION: It is recommended that Chinese residents who are consuming soybean oil choose well-known brands and regularly change their brand of consumption. The phthalates in edible vegetable oils pose a relatively small reproductive health risk to Chinese residents. © 2019 Society of Chemical Industry.

Musical training sharpens behavioral tuning more saliently than peripheral tuning.

Musical training appears to enhance performance at both peripheral and central auditory sites. We compared behavioral and peripheral frequency tuning in normal-hearing musicians and nonmusicians, whose native language is Mandarin. The results indicate that, at higher probe frequencies, musical training sharpens behavioral tuning more saliently than peripheral tuning. The improved peripheral tuning for musician appears to result principally from efferent top-down control rather than local cochlear changes.

Anemoside B4 Protects Rat Kidney from Adenine-Induced Injury by Attenuating Inflammation and Fibrosis and Enhancing Podocin and Nephrin Expression.

Anemoside B4 (B4) isolated from Radix Pulsatilla has anti-inflammatory activities in the colon and antitumor effects. However, its role in the prevention and treatment of kidney injury has not been reported. Here, we reported the effects of B4 on chronic kidney injury (CKI) and studied its related mechanism based on an adenine-induced kidney injury model in rats. The results showed that serum BUN (blood urea nitrogen), Crea (creatinine), and urinary proteins increased significantly after oral administration of adenine. Meanwhile, the adenine contents in both renal tissue and urine increased markedly compared with those of normal rats. Moreover, IL-1ß, IL-6, TNFα, and NFκB expression was upregulated in the kidney. Simultaneously, the expression of NLRP3 (the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3) in the inflammasome, which consists of Caspase 1, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and IL-18, was significantly upregulated. B4 could significantly decrease BUN and Crea; reduce urinary proteins in rats; suppress the expression of IL-6, IL-1ß, NFκB, NLRP3, Caspase 1, ASC, and IL-18; and increase urinary adenine contents and promote its excretion. In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.

[Study on acute kidney injury model induced by renal ischemia-reperfusion in rats].

In this study,in-depth systematic evaluation of rat of acute kidney injury(AKI) caused by renal arteriovenous ligation was conducted to better master and apply this model for drug research. Male SD rats of 2-3 months old were employed in this study.The left kidney was removed,and the right kidney received ligation for 40 min and reperfusion for 24 h. Serum creatinine(Crea),urea nitrogen(BUN) and the renal tissue sections were assayed as the basic indicators to evaluate their renal function. The mRNA expression of inflammatory necrosis factors and apoptotic factors was used to evaluate the mechanism of molecular pathophysiological changes. The results showed that the serum Crea and BUN caused by ligation of both renal arteries and veins were significantly higher than those of rats with renal artery ligation. After renal arteriovenous ligation for 40 min and reperfusion for 24 h in rats,the serum Crea of the rats varied from less than 100 µmol·L-1 to more than 430 µmol·L-1. Among them,5 rats showed less than 100 µmol·L-1 serum Crea,20 rats with 100-200 µmol·L-1 serum Crea and 12 rats with more than 430 µmol·L-1. Rats with serum Crea between 300-430 µmol·L-1 accounted for 66.3%(122/184) of the total number of the experiment rats. After 72 h reperfusion,serum Crea in the group of Crea 370-430 µmol·L-1 continued to increase,while the serum Crea in the group of Crea 200-300 µmol·L-1 and the group of Crea 300-370 µmol·L-1 recovered quickly. No matter serum Crea was elevated or decreased,the renal tubules showed pathological changes such as vacuolar degeneration or even necrosis. The mRNA expression levels of Toll-like receptor(TLR4),tumor necrosis factor(TNF-α) and interleukin(IL-6) in renal tissueswere significantly up-regulated,and the effect was most obvious in the group of serum Crea 370-430 µmol·L-1. The study indicated that the model for AKI caused by renal arteriovenous ligation and reperfusion is easy to operate,and the serum Crea and BUN have the characteristics of continuous increase,beneficial to the observation of drug effects. This acute kidney injury is mainly related to the pathophysiological response of inflammatory necrosis.

Effects of copper treatment on mineral nutrient absorption and cell ultrastructure of spinach seedlings.

The accumulation of heavy metals in soil has serious influence on plant growth and ecosystem balance. It is of great importance to explore the mechanism of plant tolerance to heavy me-tals. Although spinach is supposed to have strong Cu tolerance, the effects of Cu on mineral element absorption and cell ultrastructure are still unclear. In this study, the growth of spinach seedlings, the absorption of mineral elements and the ultrastructure of leaf cells were examined in a pot experiment. The results showed that Cu2+ accumulation in the root of spinach seedling was less than that in the shoot when CuSO4 concentration was 100 mg·L-1, with root growth being increased and shoot growth being slightly decreased. When copper concentration continued to increase, the growth parameters continuously declined. When the CuSO4 concentrations were less than 400 mg·L-1, the foliar N, K, Ca, Mg and Fe concentrations of spinach seedling increased, and that of P decreased. The concentrations of N, P and K in roots went down and that of Ca, Mg and Fe went up. All organelles in leaf cells were clearly visible. The basal granule layer was arranged orderly, and the inner and outer membranes of chloroplasts were intact. When the CuSO4 concentrations exceeded 600 mg·L-1, foliar N concentration increased while that of P, K, Ca, Mg and Fe decreased. The concentrations of N, P, K, Ca, Mg and Fe in roots declined. The cell ultrastructure of spinach seedlings substantially changed with the increases of CuSO4 treated concentrations. The chloroplast in leaf cells became rounder, the chloroplast membrane became thinner, the stroma and basal granule layer became less, and the layer accumulation height decreased. The nucleus was broken up and small black spots were found in vacuoles and cell walls, which might be attributed to the enhancement of intracellular swelling pressure caused by high accumulation of Cu2+. In conclusion, low concentration of CuSO4 had little negative effect on the life activities of spinach seedlings, and the high concentrations of CuSO4 did not terminate their growth, indicating that spinach seedlings had strong copper resistance.

Correlation between the frequency difference limen and an index based on principal component analysis of the frequency-following response of normal hearing listeners.

Subcortical phase locking tends to reflect performance differences in tasks related to pitch perception across different types of populations. Enhancement or attenuation in its strength may correspond to population excellence or deficiency in pitch perception. However, it is still unclear whether differences in perceptual capability among individuals with normal hearing can be predicted by subcortical phase locking. In this study, we examined the brain-behavior relationship between frequency-following responses (FFRs) evoked by pure/sweeping tones and frequency difference limens (FDLs). FFRs are considered to reflect subcortical phase locking, and FDLs are a psychophysical measure of behavioral performance in pitch discrimination. Traditional measures of FFR strength were found to be poorly correlated with FDL. Here, we introduced principal component analysis into FFR analysis and extracted an FFR component that was correlated with individual pitch discrimination. The absolute value of the score of this FFR principal component (but not the original score) was negatively correlated with FDL, regardless of stimulus type. The topographic distribution of this component was relatively constant across individuals and across stimulus types, and the inferior colliculus was identified as its origin. The findings suggest that subcortical phase locking at certain but not all FFR generators carries the neural information required for the prediction of individual pitch perception among humans with normal hearing.

Deficits in the 30-Hz auditory steady-state response in patients with major depressive disorder.

The auditory steady-state response (ASSR) is an auditory evoked potential that occurs in response to periodically presented auditory stimuli. The ASSR has drawn attention as a biomarker of psychiatric disorders owing to its connection with neural oscillations as well as its easy and noninvasive recording. Abnormalities in the γ band ASSR have been found consistently in patients with schizophrenia and bipolar disorder. However, although major depressive disorder (MDD) is also part of the common psychiatric diseases, the relationship between the ASSR and MDD has not been characterized sufficiently. Thus, the aim of the present study was to examine the ASSRs from patients with MDD and compare them with those from healthy control (HC) participants. The experiment was designed to obtain the ASSRs elicited by 20-, 30-, and 40-Hz click trains. Patients and HCs were evaluated separately. The response power and phase synchronization were measured at each stimulation frequency. Patients with MDD showed significantly reduced ASSR power for 30-Hz stimuli compared with HC participants, whereas no significant differences in the power were observed at 20 and 40 Hz for patients with MDD. In addition, no significant difference in the phase synchronization was observed for 20-, 30-, and 40-Hz stimuli. Conclusively, patients with MDD were characterized by deficits in 30-Hz ASSR power, which may be associated with spontaneous γ activity dysfunction. The present findings suggest that ASSR could potentially be used as a biomarker for MDD.

The early component of middle latency auditory-evoked potentials in the process of deviance detection.

The aim of the present study was to investigate both the encoding mechanism and the process of deviance detection when deviant stimuli were presented in various patterns in an environment featuring repetitive sounds. In adults with normal hearing, middle latency responses were recorded within an oddball paradigm containing complex tones or speech sounds, wherein deviant stimuli featured different change patterns. For both complex tones and speech sounds, the Na and Pa components of middle latency responses showed an increase in the mean amplitude and a reduction in latency when comparing rare deviant stimuli with repetitive standard stimuli in a stimulation block. However, deviant stimuli with a rising frequency induced signals with smaller amplitudes than other deviant stimuli. The present findings indicate that deviant stimuli with different change patterns induce differing responses in the primary auditory cortex. In addition, the Pa components of speech sounds typically feature a longer latency and similar mean amplitude compared with complex tones, which suggests that the auditory system requires more complex processing for the analysis of speech sounds before processing in the auditory cortex.

Design and implementation of frequency-following response recording system.

OBJECTIVE: The frequency-following response (FFR) is the compound phase-locked brainstem response to periodic components of sound stimuli, and is closely related to pitch perception. Its weak amplitude often prevents its measurement with a high signal-to-noise ratio (SNR). Recording of FFR using multichannel EEG is possible but expensive and it involves the manual screening of raw data. DESIGN: We describe a new method to extract FFR features by prescreening the raw data using automatic monitoring of sound pressure in the ear canal. Removal of stimulus artifacts, noise reduction, and data selection were systematically studied. STUDY SAMPLE: The reliability of our new method was tested by comparing FFRs tracking accuracy and pitch perception in fifteen individuals with normal hearing. RESULTS: The extracted FFRs tracking accuracy was significantly correlated with behavioral measures of pitch perception, indicating that FFR could be used to represent individual differences in pitch perception ability among a population with similar hearing characteristics. CONCLUSION: The designed system could extract FFR signals more accurately with high SNR after signal prescreen and noise reduction.

[A study on chilling injury in medicinal plants region of South China Botanical Garden].

From late January to early February in 2008, Guangzhou suffered from the cold and humid rainy for 20 days, and the daily mean temperature was under 10 degrees C. In 794 species of medicinal plants in South China Botanical Garden, 78 species (9.8%) suffered from chilling injury. The reasons were analyzed and some useful suggestions were made.