Biparametric MRI of the prostate radiomics model for prediction of pelvic lymph node metastasis in prostate cancers : a two-centre study.

OBJECTIVES: Exploring the value of adding correlation analysis (radiomic features (RFs) of pelvic metastatic lymph nodes and primary lesions) to screen RFs of primary lesions in the feature selection process of establishing prediction model. METHODS: A total of 394 prostate cancer (PCa) patients (263 in the training group, 74 in the internal validation group and 57 in the external validation group) from two tertiary hospitals were included in the study. The cases with pelvic lymph node metastasis (PLNM) positive in the training group were diagnosed by biopsy or MRI with a short-axis diameter ≥ 1.5 cm, PLNM-negative cases in the training group and all cases in validation group were underwent both radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). The RFs of PLNM-negative lesion and PLNM-positive tissues including primary lesions and their metastatic lymph nodes (MLNs) in the training group were extracted from T2WI and apparent diffusion coefficient (ADC) map to build the following two models by fivefold cross-validation: the lesion model, established according to the primary lesion RFs selected by t tests and absolute shrinkage and selection operator (LASSO); the lesion-correlation model, established according to the primary lesion RFs selected by Pearson correlation analysis (RFs of primary lesions and their MLNs, correlation coefficient > 0.9), t test and LASSO. Finally, we compared the performance of these two models in predicting PLNM. RESULTS: The AUC and the DeLong test of AUC in the lesion model and lesion-correlation model were as follows: training groups (0.8053, 0.8466, p = 0.0002), internal validation group (0.7321, 0.8268, p = 0.0429), and external validation group (0.6445, 0.7874, p = 0.0431), respectively. CONCLUSION: The lesion-correlation model established by features of primary tumors correlated with MLNs has more advantages than the lesion model in predicting PLNM.

Development and Validation of a Biparametric MRI Deep Learning Radiomics Model with Clinical Characteristics for Predicting Perineural Invasion in Patients with Prostate Cancer.

RATIONALE AND OBJECTIVES: Perineural invasion (PNI) is an important prognostic biomarker for prostate cancer (PCa). This study aimed to develop and validate a predictive model integrating biparametric MRI-based deep learning radiomics and clinical characteristics for the non-invasive prediction of PNI in patients with PCa. MATERIALS AND METHODS: In this prospective study, 557 PCa patients who underwent preoperative MRI and radical prostatectomy were recruited and randomly divided into the training and the validation cohorts at a ratio of 7:3. Clinical model for predicting PNI was constructed by univariate and multivariate regression analyses on various clinical indicators, followed by logistic regression. Radiomics and deep learning methods were used to develop different MRI-based radiomics and deep learning models. Subsequently, the clinical, radiomics, and deep learning signatures were combined to develop the integrated deep learning-radiomics-clinical model (DLRC). The performance of the models was assessed by plotting the receiver operating characteristic (ROC) curves and precision-recall (PR) curves, as well as calculating the area under the ROC and PR curves (ROC-AUC and PR-AUC). The calibration curve and decision curve were used to evaluate the model's goodness of fit and clinical benefit. RESULTS: The DLRC model demonstrated the highest performance in both the training and the validation cohorts, with ROC-AUCs of 0.914 and 0.848, respectively, and PR-AUCs of 0.948 and 0.926, respectively. The DLRC model showed good calibration and clinical benefit in both cohorts. CONCLUSION: The DLRC model, which integrated clinical, radiomics, and deep learning signatures, can serve as a robust tool for predicting PNI in patients with PCa, thus aiding in developing effective treatment strategies.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

Impaired Sensitivity to Thyroid Hormone and Risk of Carotid Plaque Development in a Chinese Health Check-Up Population: A Large Sample Cross-Sectional Study.

Objective: Previous research on the correlation between thyroid function and carotid plaque has revealed conflicting results, possibly attributable to the sensitivity of thyroid hormone indices. In this study, we aimed to analyze the association between thyroid hormone sensitivity indices and the risk of carotid plaque development in a Chinese health check-up population. Methods: A total of 19,388 health check-up subjects were included in this study (mean age: 50.78±10.17 years). Central sensitivity to thyroid hormone was evaluated using the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), while peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Multivariable logistic regression analyses were performed to detect the association between thyroid hormone sensitivity indices and carotid plaque risk, and subgroup analysis was also conducted to explore this association stratified by sex, age, obesity, and the status of smoking, drinking, diabetes, hypertension and dyslipidemia. Results: Among the 19,388 participants, 3753 (19.4%) had carotid plaque. In multivariable adjustment models, the risk of carotid plaque was positively associated with TSHI (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.18~1.28), TT4RI (OR: 1.28; 95% CI: 1.23~1.33), TFQI (OR: 1.06; 95% CI: 1.02~1.10), and PTFQI (OR: 1.11; 95% CI: 1.07~1.16), respectively. Conversely, the risk of carotid plaque was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.90~0.98). In stratified analyses, all thyroid hormone sensitivity indices significantly increased the risk of carotid plaque especially in females, subjects<65 years, non-obese individuals, and those without current smoking, drinking, diabetes, hypertension and dyslipidemia. Conclusion: In Chinese health check-up populations, a considerable connection between reduced sensitivity to thyroid hormones and carotid plaque has been observed, especially in females, those younger than 65 years, non-obese individuals, and those without any current smoking, drinking, diabetes, hypertension, or dyslipidemia.

Factors Affecting Visual-Only Speech Recognition in Individuals With Cochlear Implants.

Objectives: Several reports have underlined the benefits of speechreading (visual-only speech recognition) on speech recognition in individuals with hearing loss after cochlear implantation (CI). However, the factors that would affect the ability of speechreading are unclear. The aim of the present study is to assess the factors that affect speechreading abilities in CI users. Methods: A total of 104 participants were enrolled in this retrospective study. They viewed silent videos of sentences being spoken by a model and were tasked with repeating what they thought had been said. They were tested under audio-only and visual-only conditions. Factors (such as the age, the age of CI; <3 years old vs 3-8 years old; male vs female, etc) believed to affect speechreading abilities were analyzed. Results: The age range of the participants is 8 to 34 years. CI users showed significantly different speechreading abilities among themselves. The authors found that age and hearing loss at 3 to 8 years of age were positively related to superior speechreading recognition scores. Conclusions: CI users followed a more complex method of perceptual compensation. Those who have suffered hearing loss between 3 and 8 years of age are more sensitive to developing an advantage in speech recognition by using speechreading. Older age positively affects speechreading abilities; thus, the more experience CI has, the greater speechreading ability they may exhibit.

Preoperative EABR evaluation of auditory pathway integrity in patients with different etiology and postoperative effect estimation.

OBJECTIVES: To evaluate the effect of electrical auditory brainstem response (EABR) on the integrity evaluation of auditory pathway and the prediction of postoperative effect of cochlear implantation in patients with different etiology of hearing loss. METHODS: A total of 580 patients with neuropathic deafness who underwent cochlear implantation surgery from August 2011 to December 2020 were selected for EABR test. The preoperative EABR waveform was analyzed, and parameters such as V wave amplitude, threshold, latency and interval of each wave, and slope of V wave I/O curve were measured. Neural response telemetry (NRT) test was performed during MAP 1 month after operation, and C and T values of the machine were recorded. RESULTS: The total EABR extraction rate was 98.45% among 580 patients, including 100% for the normal structure group and enlarged vestibular aqueduct group (LVAS), 92.44% for other malformed group. The average threshold of V wave in patients with normal cochlear structure was significantly better than the malformation groups (p < 0.05). The total extraction rate of NRT was 78.62%, including 99.72% in the group with normal structure, 95.65% in the LVAS group, 1.85-88.24% in the group with other malformations, and 0% in the cochlear ossification group. The correlation analysis showed a statistically significant correlation between the average preoperative EABR threshold and the C value of NRT. CONCLUSIONS: Preoperative EABR could evaluate the integrity of auditory conduction pathway of patients with cochlear implantation and predict the postoperative hearing rehabilitation effect.

Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

Background: To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. Methods: A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. Results: The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. Conclusions: ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

T1 Mapping for Differentiating of Haemorrhagic Transformation from Extravasation of Iodine Contrast Agents: A Phantom Study.

OBJECTIVE: To evaluate T1 mapping values in different concentrations of iodine and mixed blood and to simulate the application of T1 mapping in differentiating iodine contrast extravasation and haemorrhage transformation after revascularisation in acute ischemic stroke. STUDY DESIGN: A phantom-based experimental study. Place and Duration of the Study: Department of Radiology, the Second Affiliated Hospital of Soochow University, China, from October 2020 to December 2021. METHODOLOGY: Fresh blood, pure iodine, blood-iodine mixtures (75/25, 50/50, and 25/75 ratios), and diluted iodine (at a concentration of 2.1 mmol I/L) were scanned in a phantom on 3-T MR T1 mapping imaging. A total of 10 layers in the middle section of tubes were scanned. The mean value of T1 mapping and 95% confidence interval for the investigated sample compositions were calculated and compared by ANOVA. RESULTS: The mean values (95% CI) for fresh blood, [2/3] blood +[1/3] iodine, [1/2] blood +[1/2] iodine, [1/3] blood +[2/3] iodine, and pure iodine were 2108.69 ± 1966.68-2250.71(ms), 1991.72 ± 1763.22-2220.21(ms), 1811.62 ± 1614.79-2008.45(ms), 1624.39 ± 1442.41-1806.37(ms), 1294.68 ± 1172.92-1416.44(ms), respectively. The differences between the T1 mapping values of all compositions were significant (p <0.01), except for fresh blood and the sample consisting of 67% blood. The mean value on T1 mapping (95% CI) was 1294.68 ± 1172.92-1416.44 (ms) in the samples only with diluted iodine, which was significantly different from other investigated samples (p <0.01). The intra-class correlation coefficient between the two times drawing of radiologist A was excellent (ICC=0.913, p<0.01), and between radiologists A and B was 0.99. CONCLUSION: Iodine contrast extravasation in a phantom setting might be distinguished from haemorrhagic transformation using T1 mapping. KEY WORDS: Acute ischemic stroke, Haemorrhage transformation, Contrast extravasation, Magnetic resonance imaging, T1 mapping, 3T MRI.

Corrigendum: Vestibular dysfunction is an important contributor to the aging of visuospatial ability in older adults-Data from a computerized test system.

[This corrects the article DOI: 10.3389/fneur.2022.1049806.].

Vestibular cognition assessment system: Tablet-based computerized visuospatial abilities test battery.

Introduction: The vestibular system is anatomically connected to extensive regions of the cerebral cortex, hippocampus, and amygdala. However, studies focusing on the impact of vestibular impairment on visuospatial cognition ability are limited. This study aimed to develop a mobile tablet-based vestibular cognitive assessment system (VCAS), enhance the dynamic and three-dimensional (3D) nature of the test conditions, and comprehensively evaluate the visuospatial cognitive ability of patients with vestibular dysfunction. Materials and methods: First, the VCAS assessment dimensions (spatial memory, spatial navigation, and mental rotation) and test content (weeding, maze, card rotation, and 3D driving tests) were determined based on expert interviews. Second, VCAS was developed based on Unity3D, using the C# language and ILruntime hot update framework development technology, combined with the A* algorithm, prime tree algorithm, and dynamic route rendering. Further, the online test was built using relevant game business logic. Finally, healthy controls (HC) and 78 patients with vertigo (VP) were recruited for the VCAS test. The validity of VCAS was verified using the test results of random controls. Results: In the weeding test, the HC group had a significantly longer span and faster velocity backward than did the VP group. In the 12 × 12 maze, statistically significant differences in step and time were observed between the two groups, with VP taking longer time and more steps. In the mental rotation task, no significant difference was observed between the two groups. Similarly, no significant difference was found in the performance of the two groups on maps 2, 3, and 4 in the 3D driving task. Discussion: Thus, impaired visuospatial cognition in patients with vestibular dysfunction is primarily related to spatial memory and navigation. VCAS is a clinically applicable visuospatial cognitive ability test for VP.

A nomogram based on LI-RADS features, clinical indicators and quantitative contrast-enhanced MRI parameters for predicting glypican-3 expression in hepatocellular carcinoma.

Purpose: Noninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC. Methods and materials: We retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively. Results: Blood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively. Conclusion: The nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Evaluation of auditory pathway by EABR before cochlear implantation and the postoperative effect analysis.

OBJECTIVE: To investigate the evaluation value of electrically evoked auditory brainstem response (EABR) monitoring before cochlear implantation in patients with cochlear nerve defects (CND). METHODS: A total of 54 patients with cochlear nerve defects who underwent cochlear implantation in our hospital from 2011 to 2018 were selected as the CND group, and 20 patients with normal cochlear implantation were selected as the control group. The preoperative audiological characteristics, EABR characteristics and follow-up neural response telemetry results of the two groups were retrospectively analysed, and the preoperative EABR threshold and initiation C value were subjected to linear regression and correlation analysis. RESULTS: The EABR waveform of the CND group was significantly different from the control group in terms of average wave V threshold, average dynamic range and V-wave I/O curve slope (P < 0.05). Average C value and dynamic range had a statistically significant difference from the control group (P < 0.05). Statistically significant positive correlations were found between the EABR threshold and C value, wave V I/O slope and postoperative category of auditory perception (P < 0.05). CONCLUSIONS: The EABR test can be used to evaluate the auditory pathway function before cochlear implantation and its postoperative effect in patients with CND.

Vestibular dysfunction is an important contributor to the aging of visuospatial ability in older adults-Data from a computerized test system.

Background: A convergence of research supports a key role of the vestibular system in visuospatial ability. However, visuospatial ability may decline with age. This work aims to elucidate the important contribution of vestibular function to visuospatial ability in old adults through a computerized test system. Methods: Patients with a clinical history of recurrent vertigo and at least failed one vestibular test were included in this cross-sectional study. Healthy controls of three age groups: older, middle-aged, and young adults were also involved. Visuospatial cognitive outcomes including spatial memory, spatial navigation, and mental rotation of all the groups were recorded. Comparing the performance of the visuospatial abilities between patients and age-matched controls as well as within the controls. Results: A total of 158 individuals were enrolled. Results showed that patients performed worse than the age-matched controls, with the differences in the forward span (p < 0.001), the time of the maze 8 × 8 (p = 0.009), and the time of the maze 12 × 12 (p = 0.032) being significant. For the differences in visuospatial cognitive outcomes within the controls, the younger group had a significantly better performance than the other groups. The older group and the middle-aged group had comparable performances during all the tests. Conclusions: Older patients with vestibular dysfunction had more difficulties during visuospatial tasks than age-matched controls, especially in spatial memory and spatial navigation. Within the controls, younger adults did much better than other age groups, while older adults behaved similarly to middle-aged adults. It is a valuable attempt to computerize the administration of tests for visuospatial ability.

Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy.

Arsenotherapy has been clinically exploited to treat a few types of solid tumors despite of acute promyelocytic leukemia using arsenic trioxide (ATO), however, its efficacy is hampered by inadequate delivery of ATO into solid tumors owing to the absence of efficient and biodegradable vehicles. Precise spatiotemporal control of subcellular ATO delivery for potent arsenotherapy thus remains challengeable. Herein, we report the self-activated arsenic manganite nanohybrids for high-contrast magnetic resonance imaging (MRI) and arsenotherapeutic synergy on triple-negative breast cancer (TNBC). The nanohybrids, composed of arsenic­manganese-co-biomineralized nanoparticles inside albumin nanocages (As/Mn-NHs), switch signal-silent background to high proton relaxivity, and simultaneously afford remarkable subcellular ATO level in acidic and glutathione environments, together with reduced ATO resistance against tumor cells. Then, the nanohybrids enable in vivo high-contrast T1-weighted MRI signals in various tumor models for delineating tumor boundary, and simultaneously yield efficient arsenotherapeutic efficacy through multiple apoptotic pathways for potently suppressing subcutaneous and orthotopic breast models. As/Mn-NHs exhibited the maximum tumor-to-normal tissue (T/N) contrast ratio of 205% and tumor growth inhibition rate of 88% at subcutaneous 4T1 tumors. These nanohybrids further yield preferable synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermotherapy. More importantly, As/Mn-NHs considerably induce immunogenic cell death (ICD) effect to activate the immunogenically "cold" tumor microenvironment into "hot" one, thus synergizing with immune checkpoint blockade to yield the strongest tumor inhibition and negligible metastatic foci in the lung. Our study offers the insight into clinically potential arsenotherapeutic nanomedicine for potent therapy against solid tumors.

The effect of aging on context use and reliance on context in speech: A behavioral experiment with Repeat-Recall Test.

Purpose: To elucidate how aging would affect the extent of semantic context use and the reliance on semantic context measured with the Repeat-Recall Test (RRT). Methods: A younger adult group (YA) aged between 18 and 25 and an older adult group (OA) aged between 50 and 65 were recruited. Participants from both the groups performed RRT: sentence repeat and delayed recall tasks, and subjective listening effort and noise tolerable time, under two noise types and seven signal-to-noise ratios (SNR). Performance-Intensity curves were fitted. The performance in SRT50 and SRT75 was predicted. Results: For the repeat task, the OA group used more semantic context and relied more on semantic context than the YA group. For the recall task, OA used less semantic context but relied more on context than the YA group. Age did not affect the subjective listening effort but significantly affected noise tolerable time. Participants in both age groups could use more context in SRT75 than SRT50 on four tasks of RRT. Under the same SRT, however, the YA group could use more context in repeat and recall tasks than the OA group. Conclusion: Age affected the use and reliance of semantic context. Even though the OA group used more context in speech recognition, they failed in speech information maintenance (recall) even with the help of semantic context. The OA group relied more on context while performing repeat and recall tasks. The amount of context used was also influenced by SRT.

[Analysis of intraoperative EABR characteristics and postoperative efficacy of cochlear implant in patients with tinnitus].

Objective:To investigate the characteristics of intraoperative electrically stimulated auditory brainstem responses（EABR） in patients with neural deafness and tinnitus, and to analyze the inhibitory effect of cochlear implantation on tinnitus and its correlation with auditory evoked potential. Methods:Twenty-eight adult patients with neuronal deafness accompanied by tinnitus who underwent cochlear implant surgery in the Peking Union Medical College Hospital from 2014 to 2015 were selected, and 10 age-matched patients without tinnitus with the same age were selected as the control group. Preoperative audiology, imaging and tinnitus history of the patients were retrospectively analyzed. During the operation, EABR were used to detect the auditory central functions at all levels, and the electrophysiological characteristics of the two groups were analyzed. The tinnitus handicap inventory（THI） was used to evaluate the severity of tinnitus before and after surgery, and the correlation between EABR results and THI score was analyzed. Results:There were no postoperative complications such as facial paralysis, cerebrospinal fluid leakage, meningitis, etc. , and electroacoustic reactions were observed in all 38 patients. The results of intraoperative EABR showed that there were significant differences in Ⅲ wave amplitude, Ⅴ wave amplitude and Ⅴ wave latency between tinnitus group and control group（P<0.05）. The mean C value of （162.78± 24.57）CL and the mean intraoperative EABR threshold of （158.62± 10.31） CL were collected in the two groups 12 months after starting the machine, and there was a significant correlation according to linear correlation analysis（r=0.903, P<0.01）. The total THI scores of 28 tinnitus patients were 65.00±14.93, 55.00±15.93 and 36.00±21.02 at three time points before, 1 day after and 1 year after cochlear implantation, respectively. The scores of 1 year after cochlear implantation were significantly different by ANOVA（P<0.05）, but there was no statistically significant difference 1 day after operation（P>0.05）. There was significant correlation between the intraoperative EABR wave Ⅲ amplitude and the linear correlation analysis of THI changes 1 year after operation（r=0.873, P<0.05）. Conclusion:There is significant difference in intraoperative EABR between patients with neural deafness accompanied with tinnitus and patients without tinnitus. Cochlear electrical stimulation has a good inhibitory effect on tinnitus, and intraoperative EABR can be used as a objective assessment tool for cochlear implant to inhibit tinnitus.

Differential auditory cortical development in left and right cochlear implanted children.

Unilateral aural stimulation has been shown to cause massive cortical reorganization in brain with congenital deafness, particularly during the sensitive period of brain development. However, it is unclear which side of stimulation provides most advantages for auditory development. The left hemisphere dominance of speech and linguistic processing in normal hearing adult brain has led to the assumption of functional and developmental advantages of right over left implantation, but existing evidence is controversial. To test this assumption and provide evidence for clinical choice, we examined 34 prelingually deaf children with unilateral cochlear implants using near-infrared spectroscopy. While controlling for age of implantation, residual hearing, and dominant hand, cortical processing of speech showed neither developmental progress nor influence of implantation side weeks to months after implant activation. In sharp contrast, for nonspeech (music signal vs. noise) processing, left implantation showed functional advantages over right implantation that were not yet discernable using clinical, questionnaire-based outcome measures. These findings support the notion that the right hemisphere develops earlier and is better preserved from adverse environmental influences than its left counterpart. This study thus provides, to our knowledge, the first evidence for differential influences of left and right auditory peripheral stimulation on early cortical development of the human brain.

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy.

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

Voice Emotion Recognition by Mandarin-Speaking Children with Cochlear Implants.

OBJECTIVES: Emotional expressions are very important in social interactions. Children with cochlear implants can have voice emotion recognition deficits due to device limitations. Mandarin-speaking children with cochlear implants may face greater challenges than those speaking nontonal languages; the pitch information is not well preserved in cochlear implants, and such children could benefit from child-directed speech, which carries more exaggerated distinctive acoustic cues for different emotions. This study investigated voice emotion recognition, using both adult-directed and child-directed materials, in Mandarin-speaking children with cochlear implants compared with normal hearing peers. The authors hypothesized that both the children with cochlear implants and those with normal hearing would perform better with child-directed materials than with adult-directed materials. DESIGN: Thirty children (7.17-17 years of age) with cochlear implants and 27 children with normal hearing (6.92-17.08 years of age) were recruited in this study. Participants completed a nonverbal reasoning test, speech recognition tests, and a voice emotion recognition task. Children with cochlear implants over the age of 10 years also completed the Chinese version of the Nijmegen Cochlear Implant Questionnaire to evaluate the health-related quality of life. The voice emotion recognition task was a five-alternative, forced-choice paradigm, which contains sentences spoken with five emotions (happy, angry, sad, scared, and neutral) in a child-directed or adult-directed manner. RESULTS: Acoustic analyses showed substantial variations across emotions in all materials, mainly on measures of mean fundamental frequency and fundamental frequency range. Mandarin-speaking children with cochlear implants displayed a significantly poorer performance than normal hearing peers in voice emotion perception tasks, regardless of whether the performance is measured in accuracy scores, Hu value, or reaction time. Children with cochlear implants and children with normal hearing were mainly affected by the mean fundamental frequency in speech emotion recognition tasks. Chronological age had a significant effect on speech emotion recognition in children with normal hearing; however, there was no significant correlation between chronological age and accuracy scores in speech emotion recognition in children with implants. Significant effects of specific emotion and test materials (better performance with child-directed materials) in both groups of children were observed. Among the children with cochlear implants, age at implantation, percentage scores of nonverbal intelligence quotient test, and sentence recognition threshold in quiet could predict recognition performance in both accuracy scores and Hu values. Time wearing cochlear implant could predict reaction time in emotion perception tasks among children with cochlear implants. No correlation was observed between the accuracy score in voice emotion perception and the self-reported scores of health-related quality of life; however, the latter were significantly correlated with speech recognition skills among Mandarin-speaking children with cochlear implants. CONCLUSIONS: Mandarin-speaking children with cochlear implants could have significant deficits in voice emotion recognition tasks compared with their normally hearing peers and can benefit from the exaggerated prosody of child-directed speech. The effects of age at cochlear implantation, speech and language development, and cognition could play an important role in voice emotion perception by Mandarin-speaking children with cochlear implants.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.