Corrigendum: EEG spectral and microstate analysis originating residual inhibition of tinnitus induced by tailor-made notched music training.

[This corrects the article DOI: 10.3389/fnins.2023.1254423.].

Factors influencing rapid antiretroviral therapy initiation in Jiulongpo, Chongqing, China: a retrospective cohort from 2018 to 2022.

BACKGROUND: Antiretroviral Therapy (ART) is pivotal in extending the lives of people living with HIV (PLWH) and minimizing transmission. Rapid ART initiation, defined as commencing ART within seven days of HIV diagnosis, is recommended for all PLWH. METHOD: A retrospective cohort study was conducted using data from the China Information System for Disease Control and Prevention. This study included PLWH diagnosed between January 2018 and December 2021 and treated by December 2022. Factors influencing rapid ART initiation were examined using univariate and multivariate Cox regression analyses. RESULTS: The study analyzed 1310 cases. The majority were male (77.4%), over 50 years old (46.7%), and contracted HIV through heterosexual transmission (70.0%). Rapid ART initiation was observed in 36.6% (n = 479) of cases, with a cumulative treatment rate of 72.9% within 30 days post-diagnosis. Heterosexual contact was associated with longer intervals from diagnosis to treatment initiation compared to homosexual contact (Adjusted Hazard Ratio (HR) = 0.813, 95% Confidence Interval (CI): 0.668-0.988). Individuals older than 50 years (Adjusted HR = 1.852, 95%CI: 1.149-2.985) were more likely to initiate ART rapidly. Conversely, treatment at the Second Public Hospital (Adjusted HR = 0.483, 95% CI: 0.330-0.708) and a CD4 cell counts above 500 (Adjusted HR = 0.553, 95% CI: 0.332-0.921) were associated with a lower likelihood of initiating treatment within seven days. CONCLUSIONS: A higher CD4 cell counts and receiving care in local public hospitals may deter rapid ART initiation. Providing CD4 counts results at diagnosis and offering testing and treatment in the same facility could enhance the rate of rapid ART initiation.

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.

EEG spectral and microstate analysis originating residual inhibition of tinnitus induced by tailor-made notched music training.

Tailor-made notched music training (TMNMT) is a promising therapy for tinnitus. Residual inhibition (RI) is one of the few interventions that can temporarily inhibit tinnitus, which is a useful technique that can be applied to tinnitus research and explore tinnitus mechanisms. In this study, RI effect of TMNMT in tinnitus was investigated mainly using behavioral tests, EEG spectral and microstate analysis. To our knowledge, this study is the first to investigate RI effect of TMNMT. A total of 44 participants with tinnitus were divided into TMNMT group (22 participants; ECnm, NMnm, RInm represent that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by TMNMT music, respectively) and Placebo control group (22 participants; ECpb, PBpb, RIpb represent that EEG recordings with eyes closed stimuli-pre, stimuli-ing, stimuli-post by Placebo music, respectively) in a single-blind manner. Behavioral tests, EEG spectral analysis (covering delta, theta, alpha, beta, gamma frequency bands) and microstate analysis (involving four microstate classes, A to D) were employed to evaluate RI effect of TMNMT. The results of the study showed that TMNMT had a stronger inhibition ability and longer inhibition time according to the behavioral tests compared to Placebo. Spectral analysis showed that RI effect of TMNMT increased significantly the power spectral density (PSD) of delta, theta bands and decreased significantly the PSD of alpha2 band, and microstate analysis showed that RI effect of TMNMT had shorter duration (microstate B, microstate C), higher Occurrence (microstate A, microstate C, microstate D), Coverage (microstate A) and transition probabilities (microstate A to microstate B, microstate A to microstate D and microstate D to microstate A). Meanwhile, RI effect of Placebo decreased significantly the PSD of alpha2 band, and microstate analysis showed that RI effect of Placebo had shorter duration (microstate C, microstate D), higher occurrence (microstate B, microstate C), lower coverage (microstate C, microstate D), higher transition probabilities (microstate A to microstate B, microstate B to microstate A). It was also found that the intensity of tinnitus symptoms was significant positively correlated with the duration of microstate B in five subgroups (ECnm, NMnm, RInm, ECpb, PBpb). Our study provided valuable experimental evidence and practical applications for the effectiveness of TMNMT as a novel music therapy for tinnitus. The observed stronger residual inhibition (RI) ability of TMNMT supported its potential applications in tinnitus treatment. Furthermore, the temporal dynamics of EEG microstates serve as novel functional and trait markers of synchronous brain activity that contribute to a deep understanding of the neural mechanism underlying TMNMT treatment for tinnitus.

Functional characterization of two flavone synthase II members in citrus.

Polymethoxylated flavones (PMFs), the main form of flavones in citrus, are derived from the flavone branch of the flavonoid biosynthesis pathway. Flavone synthases (FNSs) are enzymes that catalyze the synthesis of flavones from flavanones. However, the FNS in citrus has not been characterized yet. Here, we identified two type II FNSs, designated CitFNSII-1 and CitFNSII-2, based on phylogenetics and transcriptome analysis. Both recombinant CitFNSII-1 and CitFNSII-2 proteins directly converted naringenin, pinocembrin, and liquiritigenin to the corresponding flavones in yeast. In addition, transient overexpression of CitFNSII-1 and CitFNSII-2, respectively, in citrus peel significantly enhanced the accumulation of total PMFs, while virus-induced CitFNSII-1 and CitFNSII-2 genes silencing simultaneously significantly reduced the expression levels of both genes and total PMF content in citrus seedlings. CitFNSII-1 and CitFNSII-2 presented distinct expression patterns in different cultivars as well as different developmental stages. Methyl salicylate (MeSA) treatment reduced the CitFNSII-2 expression as well as the PMFs content in the peel of Citrus sinensis fruit but did not affect the CitFNSII-1 expression. These results indicated that both CitFNSII-1 and CitFNSII-2 participated in the flavone biosynthesis in citrus while the regulatory mechanism governing their expression might be specific. Our findings improved the understanding of the PMFs biosynthesis pathway in citrus and laid the foundation for further investigation on flavone synthesis regulation.

Low-dose lipopolysaccharide inducing continuous and obvious increase in urinary protein in hyperglycemic rats and the underlying mechanism.

Proteinuria is an important hallmark of diabetic nephropathy models, however it takes a long time for the proteinuria and is not stable. Therefore, low-dose lipopolysaccharide (LPS) was investigated in this work to induce rapid and stable proteinuria in hyperglycemic rats and the underlying mechanism was studied. Hyperglycemia rats was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ). After 21 days, the model rats received a subinjury dose of 0.8 mg / kg LPS intraperitoneally (i.p.). We detected related biochemical indexes at different time periods after LPS injection and examined the expression of glomerular podocyte-associated proteins. Simultaneously, we measured expression of inflammatory factors, apoptotic proteins and albumin (ALB) in the renal cortex and renal medulla, respectively. PAS (Periodic Acid Schiff) staining was used to observe renal pathology. After LPS injection, urinary microalbumin (umALB) increased significantly and lasted longer. The expression of Nephrin, Podocin and necroptosis factor kappa B (NF-κB) in rennal cortex and Interleukin 18 (IL-18), Caspase-1, NF-κB and ALB in the renal medulla was significantly changed. Pathologically, the glomerular basement membrane was observed to be significantly thickened, the renal tubules were dilated, and the epithelial cells fell off in a circle. LPS promoted the continuous increase in urinary microalbumin in hyperglycemic rats, which was related to the damage to the glomerular basement membrane and renal tubular epithelial cells and to the inflammatory reaction in the kidney involved in NF-κB signaling, and this pathological damage can help to establish a stable model of diabetic nephropathy with increased proteinuria.

Genome-wide analysis of cytochrome P450 genes in Citrus clementina and characterization of a CYP gene encoding flavonoid 3'-hydroxylase.

Cytochrome P450s (CYPs) are the largest family of enzymes in plant and play multifarious roles in development and defense but the available information about the CYP superfamily in citrus is very limited. Here we provide a comprehensive genome-wide analysis of the CYP superfamily in Citrus clementina genome, identifying 301 CYP genes grouped into ten clans and 49 families. The characteristics of both gene structures and motif compositions strongly supported the reliability of the phylogenetic relationship. Duplication analysis indicated that tandem duplication was the major driving force of expansion for this superfamily. Promoter analysis revealed numerous cis-acting elements related to various responsiveness. RNA-seq data elucidated their expression patterns in citrus fruit peel both during development and in response to UV-B. Furthermore, we characterize a UV-B-induced CYP gene (Ciclev10019637m, designated CitF3'H) as a flavonoid 3'-hydroxylase for the first time. CitF3'H catalyzed numerous flavonoids and favored naringenin in yeast assays. Virus-induced silencing of CitF3'H in citrus seedlings significantly reduced the levels of 3'-hydroxylated flavonoids and their derivatives. These results together with the endoplasmic reticulum-localization of CitF3'H in plant suggest that this enzyme is responsible for the biosynthesis of 3'-hydroxylated flavonoids in citrus. Taken together, our findings provide extensive information about the CYP superfamily in citrus and contribute to further functional verification.

Anemoside B4 Exerts Hypoglycemic Effect by Regulating the Expression of GLUT4 in HFD/STZ Rats.

Anemoside B4 (B4) is a saponin that is extracted from Pulsatilla chinensis (Bge.), and Regel exhibited anti-inflammatory, antioxidant, antiviral, and immunomodulatory activities. However, its hypoglycemic activity in diabetes mellitus has not been evaluated. Here, we explored the effect of B4 on hyperglycemia and studied its underlying mechanism of lowering blood glucose based on hyperglycemic rats in vivo and L6 skeletal muscle cells (L6) in vitro. The rats were fed a high-fat diet (HFD) for one month, combined with an intraperitoneal injection of 60 mg/kg streptozotocin (STZ) to construct the animal model, and the drug was administrated for two weeks. Blood glucose was detected and the proteins and mRNA were expressed. Our study showed that B4 significantly diminished fasting blood glucose (FBG) and improved glucose metabolism. In addition, B4 facilitated glucose utilization in L6 cells. B4 could enhance the expression of glucose transporter 4 (GLUT4) in rat skeletal muscle and L6 cells. Mechanistically, B4 elevated the inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Furthermore, we confirmed the effect of B4 on glucose uptake involved in the enhancement of GLUT4 expression in part due to PI3K/AKT signaling by using a small molecule inhibitor assay and constructing a GLUT4 promoter plasmid. Taken together, our study found that B4 ameliorates hyperglycemia through the PI3K/AKT pathway and promotes GLUT4 initiation, showing a new perspective of B4 as a potential agent against diabetes.

Comparative chloroplast genome analyses of diverse Phoebe (Lauraceae) species endemic to China provide insight into their phylogeographical origin.

The genus Phoebe (Lauraceae) includes about 90 evergreen tree species that are an ideal source of timber. Habitat destruction and deforestation have resulted in most of them being endemic to China. The accurate identification of endangered Phoebe species in China is necessary for their conservation. Chloroplast genome sequences can play an important role in species identification. In this study, comparative chloroplast genome analyses were conducted on diverse Phoebe species that are primarily distributed in China. Despite the conserved nature of chloroplast genomes, we detected some highly divergent intergenic regions (petA-psbE, ndhF-rpl32, and psbM-trnD-GUC) as well as three highly divergent genes (rbcL, ycf1, and ycf2) that have potential applications in phylogenetics and evolutionary analysis. The phylogenetic analysis indicated that various Phoebe species in China were divided into three clades. The complete chloroplast genome was better suited for phylogenetic analysis of Phoebe species. In addition, based on the phylogeographical analysis of Phoebe species in China, we inferred that the Phoebe species in China first originated in Yunnan and then spread to other southern areas of the Yangtze River. The results of this research will add to existing case studies on the phylogenetic analysis of Phoebe species and have the potential to contribute to the conservation of Phoebe species that are in danger of extinction.

Surface Modification of lactose carrier particles using a fluid bed coater to improve fine particle fraction for dry powder inhalers.

Surface roughness of carrier particles can impact dry powder inhaler (DPI) performance. There are opposing views on the effect of roughness on DPI performance. Hence, a systematic approach is needed to modify carrier surfaces and evaluate the impact on drug delivery. Carrier particle surfaces were modified by fluid bed coating with saturated lactose containing micronized lactose of different sizes (2, 5 and 8 µm) and coated to different levels (20, 40, 60 and 80%). Their drug delivery performance was assessed by the fine particle fraction (FPF). Roughness parameters, mean arithmetic roughness (Ra) and arithmetic mean height (Sa), of the carrier particles, were also evaluated using optical profilometry and scanning laser microscopy. Generally, particles of higher Ra had higher FPF. Higher Sa resulted in higher FPF only for particles with 60 and 80% coat levels. Reduced contact surface area between the drug particle and rougher carrier particle resulted in easier drug detachment during aerosolization. The 5 µm micronized lactose produced optimal carrier particles with respect to FPF and surface roughness. The study highlighted that with the ideal particles for surface roughening and coating level, surface roughening could be efficiently achieved by fluid bed coating for superior DPI performance.

Corrigendum: EEG spectral and microstate analysis originating residual inhibition of tinnitus induced by tailor-made notched music training.

[This corrects the article DOI: 10.3389/fnins.2023.1254423.].

Global, regional, and national burden of uterine fibroids in the last 30 years: Estimates from the 1990 to 2019 Global Burden of Disease Study.

Objective: To study specific information on trends in incidence, mortality, disability-adjusted life years (DALY) and the corresponding trends among five sociodemographic index regions, 21 regions, and 204 countries for decision-making, which would enable policymakers to distribute limited resources and devise policies more rationally. Methods: Data on uterine fibroids (UNs) from 1990 to 2019, including incidence, mortality, and DALYs, were obtained from the 2019 Global Burden of Disease Study. An estimated annual percentage change (EAPC) was calculated to assess morbidity, mortality, and DALY trends. Results: The incident cases of UFs increased from 5,769,658 (95%UI, 7,634,3995-4,274,824) incidences in 1990 to 9,643,336 (95%UI, 7,178,053-12,714,741) incidences in 2017, and the age-standardized incidence rate was steady at 225.67/100,000 persons (95%UI, 167.33-298.87) in 1990 to 241.18/100,000 persons (95%UI, 179,45-318.02) in 2019. The incidence ratio in the high sociodemographic index (SDI) region showed a unimodal distribution, with peaks in 2005. Between 2009 and 2017, the age-standardized death rate of UFs declined globally, especially in low-SDI and low-middle SDI regions. In contrast with 860,619 DALYs (95%UI, 473,067-1,505,289) in 1990, the number of DALYs was 1,378,497 (95%UI, 710,915-2,475,244) in 2019, which had increased significantly, whereas the age-standardized DALY rate decreased expressively with an EAPC of -1.93 (95%CI, from -2.16 to -1.71). Conclusion: The global burden of UFs increased between 1990 and 2019, and the incidences and DALYs increased prominently worldwide, while the deaths from UFs had no evident growth. Lower SDI regions carried an incremental burden of UFs, while disease reduction was observed in higher SDI regions. It is high time we paid attention to the underprivileged regional quality of life and health protection.

Integrated genomic, transcriptomic, and epigenetic analyses identify a leukotriene synthesis-related M2 macrophage gene signature that predicts prognosis and treatment vulnerability in gliomas.

The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesis-related gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease.

Association between maternal breastfeeding and risk of systemic neoplasms of offspring.

BACKGROUND: Breastfeeding might prevent childhood cancer by stimulating the immune system. METHODS: The following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021. RESULTS: In dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin's lymphoma (HL), or non-HL. CONCLUSIONS: The evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.

Cognitive behavioral therapy for children and adolescents with post-traumatic stress disorder: meta-analysis.

BACKGROUND: Children and adolescents who experience traumatic events may develop post-traumatic stress disorder (PTSD), which is often associated with other psychiatric disorders, including depression and anxiety. Cognitive behavioral therapy (CBT) is widely used in psychotherapy to treat PTSD in children and adolescents. This meta-analysis evaluated previous studies on the effectiveness of CBT in the treatment of PTSD in children and adolescents. METHODS: Randomized controlled trials (RCTs) published before July 25, 2021, were retrieved from seven databases. All RCTs of CBT compared to control, including conventional treatment or other treatments, in children or adolescents with PTSD. Random effect models were employed for all outcomes. Risk of bias was performed by Cochrane Collaboration's tool. The publication bias was evaluated using the Egger's regression analysis. RESULTS: Nineteen RCTs were included in the meta-analysis. Compared with control, CBT was effective in reducing the symptoms of PTSD in children and adolescents, with a variety of scales used to measure the overall PTSD symptoms: CAPS (SMD = -0.41, 95%CI [-0.71, -0.12]), CPSS (SMD = -0.88, 95%CI [-1.42, -0.34]) and UCLA-PTSD RI (SMD = -1.70, 95%CI [-2.98, -0.42]). Furthermore, CBT also improved the comorbidities of depression (SMD = -0.43, 95%CI [-0.70, -0.17]) and anxiety (SMD = -0.29, 95%CI [-0.56, -0.03]) associated with PTSD. However, CBT was not effective in reducing avoidance symptoms (SMD = 0.38, 95%CI [-0.55, 1.31]). CONCLUSION: CBT can reduce the severity of PTSD in children and adolescents and improve the symptoms of depression and anxiety, as evident in the treatment of PTSD victims of sexual abuse and war and in patients aged more than 7 years.

Complete chloroplast genome sequence and annotation of Actinodaphne lecomtei C.K.Allen, 1938 (Lauraceae).

Actinodaphne lecomtei C.K.Allen, 1938 is an evergreen tree of the Lauraceae family and grows at the mountainous areas of southwestern China. In this study, we presented the first complete chloroplast genome sequence of A. lecomtei. We analyzed the chloroplast genome structure of A. lecomtei and performed a phylogenetic analysis. The complete chloroplast genome of A. lecomtei was 152,863 bp in length which contains a large single-copy (LSC) region of 93,763 bp, a small single-copy (SSC) region of 18,814 bp, and two inverted repeat (IR) regions of 20,143 bp. The analysis identified 128 genes, comprised of 84 protein-coding genes, 36 tRNAs, and eight rRNAs. The GC content of A. lecomtei complete chloroplast genome was 39.1%. The phylogenetic analysis result demonstrated that A. lecomtei was closely related to A. obovate.

The abrupt pathological deterioration of cisplatin-induced acute kidney injury: Emerging of a critical time point.

Cisplatin (CP), an anticancer drug, often causes kidney damage. However, the mechanism of CP-induced acute kidney injury (AKI) is not completely understood. AKI was induced by intravenous injection (i.v.) of cisplatin at doses of 5, 8, and 10 mg/kg. Anemoside B4 (B4) (20 mg/kg, i.m.) and dexamethasone (DXM) (0.5 mg/kg, i.v.) were used for AKI treatment. Biochemical indicators were assessed using an automatic biochemical analyzer, protein expression was analyzed by western blotting, and morphological changes in the kidney were examined by PAS staining. The serum creatinine (Cre) and blood urea nitrogen (BUN) levels did not change significantly in the first 2 days but abruptly increased on the third day after CP injection. The serum albumin (ALB) and total protein (TP) levels decreased in both a time- and dose-dependent manner. The urine protein level increased, the clearing rate of Cre decreased distinctly, and morphologic changes appeared in a dose-dependent manner. The protein expression of p53/caspase-3, NLRP3, IL-6, and TNF-α was obviously upregulated on day 3; concurrently, nephrin and podocin were downregulated. The expression of LC3II and p62 was upregulated significantly as the CP dose increased. B4 and DXM obviously decreased the BUN and Cre levels after 3 or 5 days of treatment. AKI appeared distinctly in a time-dependent manner at 2 to 5 days after the administration of 5 mg/kg CP and in a dose-dependent manner upon the administration of 5, 8, and 10 mg/kg CP. The third day was a significant time point for renal deterioration, and treatment with B4 and DXM within the first 3 days provided significant protection against AKI.

Objective Assessment System for Hearing Prediction Based on Stimulus-Frequency Otoacoustic Emissions.

Stimulus-frequency otoacoustic emissions (SFOAEs) can be useful tools for assessing cochlear function noninvasively. However, there is a lack of reports describing their utility in predicting hearing capabilities. Data for model training were collected from 245 and 839 ears with normal hearing and sensorineural hearing loss, respectively. Based on SFOAEs, this study developed an objective assessment system consisting of three mutually independent modules, with the routine test module and the fast test module used for threshold prediction and the hearing screening module for identifying hearing loss. Results evaluated via cross-validation show that the routine test module and the fast test module predict hearing thresholds with similar performance from 0.5 to 8 kHz, with mean absolute errors of 7.06-11.61 dB for the routine module and of 7.40-12.60 dB for the fast module. However, the fast module involves less test time than is needed in the routine module. The hearing screening module identifies hearing status with a large area under the receiver operating characteristic curve (0.912-0.985), high accuracy (88.4-95.9%), and low false negative rate (2.9-7.0%) at 0.5-8 kHz. The three modules are further validated on unknown data, and the results are similar to those obtained through cross-validation, indicating these modules can be well generalized to new data. Both the routine module and fast module are potential tools for predicting hearing thresholds. However, their prediction performance in ears with hearing loss requires further improvement to facilitate their clinical utility. The hearing screening module shows promise as a clinical tool for identifying hearing loss.

Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy.

Interferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were collected. Various bioinformatics algorithms were employed to establish a gene signature that characterizes immunological features, genomic alterations, and clinical characteristics associated with the IFNG response. In this way, a novel IFNG-related gene signature (IFNGrGS, including TGFBI, IL4I1, ACP5, and LUM) has been constructed and validated. Samples with increased IFNGrGS scores were characterized by increased neutrophil and macrophage infiltration and exuberant innate immune responses, while the activated adaptive immune response may be frustrated by multiple immunosuppressive mechanisms. Notably, the IFNG pathway as well as its antagonistic pathways including IL4, IL10, TGF-beta, and VEGF converged on the expression of immune checkpoints. Besides, gene mutations involved in the microenvironment were associated with the IFNGrGS-based stratification, where the heterogeneous prognostic significance of EGFR mutation may be related to the different degrees of IFNG response. Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM.

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.