Low-dimensional interference of mid-level sound statistics predicts human speech recognition in natural environmental noise.

Recognizing speech in noise, such as in a busy street or restaurant, is an essential listening task where the task difficulty varies across acoustic environments and noise levels. Yet, current cognitive models are unable to account for changing real-world hearing sensitivity. Here, using natural and perturbed background sounds we demonstrate that spectrum and modulations statistics of environmental backgrounds drastically impact human word recognition accuracy and they do so independently of the noise level. These sound statistics can facilitate or hinder recognition - at the same noise level accuracy can range from 0% to 100%, depending on the background. To explain this perceptual variability, we optimized a biologically grounded hierarchical model, consisting of frequency-tuned cochlear filters and subsequent mid-level modulation-tuned filters that account for central auditory tuning. Low-dimensional summary statistics from the mid-level model accurately predict single trial perceptual judgments, accounting for more than 90% of the perceptual variance across backgrounds and noise levels, and substantially outperforming a cochlear model. Furthermore, perceptual transfer functions in the mid-level auditory space identify multi-dimensional natural sound features that impact recognition. Thus speech recognition in natural backgrounds involves interference of multiple summary statistics that are well described by an interpretable, low-dimensional auditory model. Since this framework relates salient natural sound cues to single trial perceptual judgements, it may improve outcomes for auditory prosthetics and clinical measurements of real-world hearing sensitivity.

Case Report: A Novel Mutation Identified in CHST14 Gene in a Fetus With Structural Abnormalities.

Background: Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a rare heritable connective tissue disease with various symptoms. The diagnosis of mcEDS is difficult because of the large overlap of clinical symptoms between different EDS subtypes. Methods: We performed karyotype analysis, gene copy number variation detection, whole-exome sequencing, and Sanger sequencing to reveal the underlying genetic etiology of a fetus with structural abnormalities in feet and kidneys. Results: A likely pathogenic mutation [NM_130468.3 c.958C>T (p.Arg320*)] and an uncertain significance mutation [NM_130468.3 c.896A>G (p.Tyr299Cys)] were identified in the carbohydrate sulfotransferase 14 (CHST14) gene by whole-exome sequencing and validated by Sanger sequencing. Conclusion: The two identified mutations appear highly likely to be the genetic causes of the fetal structural abnormalities.

Five candidate biomarkers associated with the diagnosis and prognosis of cervical cancer.

PURPOSE: Cervical cancer (CC) is one of the most general gynecological malignancies and is associated with high morbidity and mortality. We aimed to select candidate genes related to the diagnosis and prognosis of CC. METHODS: The mRNA expression profile datasets were downloaded. We also downloaded RNA-sequencing gene expression data and related clinical materials from TCGA, which included 307 CC samples and 3 normal samples. Differentially expressed genes (DEGs) were obtained by R software. GO function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were performed in the DAVID dataset. Using machine learning, the optimal diagnostic mRNA biomarkers for CC were identified. We used qRT-PCR and Human Protein Atlas (HPA) database to exhibit the differences in gene and protein levels of candidate genes. RESULTS: A total of 313 DEGs were screened from the microarray expression profile datasets. DNA methyltransferase 1 (DNMT1), Chromatin Assembly Factor 1, subunit B (CHAF1B), Chromatin Assembly Factor 1, subunit A (CHAF1A), MCM2, CDKN2A were identified as optimal diagnostic mRNA biomarkers for CC. Additionally, the GEPIA database showed that the DNMT1, CHAF1B, CHAF1A, MCM2 and CDKN2A were associated with the poor survival of CC patients. HPA database and qRT-PCR confirmed that these genes were highly expressed in CC tissues. CONCLUSION: The present study identified five DEmRNAs, including DNMT1, CHAF1B, CHAF1A, MCM2 and Kinetochore-related protein 1 (KNTC1), as potential diagnostic and prognostic biomarkers of CC.

Distinct neural ensemble response statistics are associated with recognition and discrimination of natural sound textures.

The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends: the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.

A neural ensemble correlation code for sound category identification.

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1-2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds.

High Expression Levels of Fascin-1 Protein in Human Gliomas and its Clinical Relevance.

INTRODUCTION: The fascin-1 protein is a cytoskeleton-like protein, which can prompt structural changes in cell membranes and affect the integrity of intercellular relations to promote invasion and metastasis of tumor cells. In this study, we researched the expression of fascin-1 in glioma. MATERIAL AND METHODS: The fascin-1 protein and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Then, we analyzed the relationship between the expression of fascin-1 protein and the clinical pathological characteristics of patients with glioma. Finally, the fascin-1 protein expression status and prognosis of glioma patients were investigated. RESULTS: The fascin-1 protein was mainly located in the cytoplasm of cells from glioma. The high expression rate of fascin-1 protein in glioma tissue was higher than that of normal brain tissue. At same time, we found that high fascin-1 protein expression was significantly correlated with World Health Organization (WHO) grading of glioma patients. The results survival analysis suggested high expression of fascin-1 protein in glioma patients with a shorter survival time. Multivariate analysis showed that high expression of fascin-1 protein was an independent predictor of the prognosis of patients with glioma. CONCLUSIONS: High expression of the fascin-1 protein indicates poor prognosis for glioma patients.

Static Characteristics of a New Three-Dimensional Linear Homeomorphic Saccade Model.

A linear homeomorphic saccade model that produces 3D saccadic eye movements consistent with physiological and anatomical evidence is introduced. Central to the model is the implementation of a time-optimal controller with six linear muscles and pulleys that represent the saccade oculomotor plant. Each muscle is modeled as a parallel combination of viscosity [Formula: see text] and series elasticity [Formula: see text] connected to the parallel combination of active-state tension generator [Formula: see text], viscosity element [Formula: see text], and length tension elastic element [Formula: see text]. Additionally, passive tissues involving the eyeball include a viscosity element [Formula: see text], elastic element [Formula: see text], and moment of inertia [Formula: see text]. The neural input for each muscle is separately maintained, whereas the effective pulling direction is modulated by its respective mid-orbital constraint from the pulleys. Initial parameter values for the oculomotor plant are based on anatomical and physiological evidence. The oculomotor plant uses a time-optimal, 2D commutative neural controller, together with the pulley system that actively functions to implement Listing's law during both static and dynamic conditions. In a companion paper, the dynamic characteristics of the saccade model is analyzed using a time domain system identification technique to estimate the final parameter values and neural inputs from saccade data. An excellent match between the model estimates and the data is observed, whereby a total of 20 horizontal, 5 vertical, and 64 oblique saccades are analyzed.

Dynamic Characteristics of a New Three-Dimensional Linear Homeomorphic Saccade Model.

A linear homeomorphic eye movement model that produces 3D saccadic eye movements consistent with anatomical and physiological evidence is introduced in this second part of a two-paper sequence. Central to the model is the implementation of a time-optimal neural control strategy involving six linear muscle models that faithfully represent the dynamic characteristics of 3D saccades. The muscle is modeled as a parallel combination of viscosity [Formula: see text] and series elasticity [Formula: see text], connected to the parallel combination of active-state tension generator [Formula: see text], viscosity element [Formula: see text], and length tension elastic element [Formula: see text]. The neural input for each muscle is separately maintained while the effective pulling direction is modulated by its respective pulley. The results demonstrate that a time-optimal, 2D commutative neural controller, together with the pulley system, actively functions to implement Listing's law during both static and dynamic simulations and provide an excellent match with the experimental data. The parameters and neural input to the muscles are estimated using a time domain system identification technique from saccade data, with an excellent match between the model estimates and the data. A total of 20 horizontal, 5 vertical and 62 oblique saccades are analyzed.

Diagnosis and treatment of carcinosarcoma of the renal pelvis: A case report.

Carcinosarcoma is a rare type of renal pelvis malignancy, the diagnosis of which requires the presence of malignant epithelial and mesenchymal components. The prognosis of this disease is extremely poor due to its rapid progression and widespread metastases. The present study describes a case of carcinosarcoma involving the right renal pelvis in a 73-year-old female who presented with intermittent hematuria and right-flank pain that had persisted for one month. Computed tomography revealed a 2.4×2.5 cm mass in the right renal pelvis, which was diagnosed as a right renal pelvic tumor. Laparoscopic radical resection of the right kidney and ureter was performed. Following surgery, immunohistochemical analysis showed positive reactions for epithelial and mesenchymal markers. Based on these findings, the patient was diagnosed with carcinosarcoma. Thus, immunohistochemical analysis is a critical method for the accurate diagnosis of carcinosarcoma.

Prevalence estimates for primary brain tumors in China: a multi-center cross-sectional study.

BACKGROUND: Although the first leading cause of death in China was malignant neoplasms (mortality, 374.1 per 100,000 person-years), the full impact of primary brain tumors (PBT) on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors. This study aimed to report a comprehensive assessment on the prevalence of PBT. METHODS: A multicenter cross-sectional study on brain tumor (MCSBT) in China was initiated in five regional centers: Daqing (northeast), Puyang (north of China), Shiyan (center of China), Ma'anshan (center of China) and Shanghai (southeast). Prevalence rate was calculated by counting the number of people living with a PBT between October 1, 2005 and September 30, 2006 and dividing by the total population of the five communities at January 1, 2006. Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories. Within these strata, the rates were estimated with 95% confidence intervals (CI) using the accurate calculation of CI for Poisson distribution. A chi-square test was used to compare the various frequencies with α < 0.05. Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of the Chinese population in 2010, obtained from World population prospects: the 2008 revision. RESULTS: We estimated that the overall prevalence of PBT was 24.56 per 100,000 (95%CI, 14.85 to 34.27), and the overall prevalence of PBT in female population (30.57 per 100,000 and its 95%CI ranged from 19.73 to 41.41) was higher than that in male population (18.84 per 100,000 and its 95%CI ranged from 10.33 to 27.35). However, the discrepancy between genders was not statistically significant because the 95%CI overlapped. Of 272 cases of newly diagnosed PBT, the proportion of histological subtypes by age groups, gender was statistically different (χ(2) = 52.6510, P < 0.0001). More than half of all reported tumors (52.57%) were either gliomas or meningiomas. For the youngest (aged from 0 - 19) strata of the population, glioma appeared to occur more than other subtypes, accounting for 55.56% of all of cases. The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas (45.12%) and gliomas (31.10%). Opposed to brain tumors in adults and teenage, gliomas only accounted for 22.22%. Meanwhile, the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas (male: 59 years old; female: 45 years old). CONCLUSIONS: Age standardized prevalence of PBT is 22.52 per 100,000 (95%CI, 13.22 to 31.82) for all populations, 17.64 per 100,000 (95%CI, 9.41 to 25.87) for men, and 27.94 per 100,000 (95%CI, 17.58 to 38.30) for women. Age standardization to China's 2010 population yielded an estimated population of 304 954 cases with PBT. Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving. In the future, it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary.

4-{[2-(2,4-Dinitro-phen-yl)hydrazinyl-idene]meth-yl}phenol ethanol hemisolvate.

In the title compound, C(13)H(10)N(4)O(5)·0.5C(2)H(5)OH, the two benzene rings form a dihedral angle of 4.29 (9)°. The ethanol solvent mol-ecule was treated as disordered between two orientations related by symmetry (center of inversion), with occupancies fixed at 0.5. The crystal packing, stabilized by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds and π-π inter-actions [indicated by the short distance of 3.7299 (7) Šbetween the centroids of benzene rings from neighbouring mol-ecules], exhibits short inter-molecular O⋯O contacts of 2.8226 (3) Å.

(E)-2-[1-(3-Chloro-4-fluoro-phen-yl)ethyl-idene]hydrazinecarbothio-amide.

In the crystal of the title compound, C(9)H(9)ClFN(3)S, the molecules are inter-connected by N-H⋯S and N-H⋯F hydrogen bonds. There are two different N-H⋯S hydrogen bond: the stronger one links mol-ecules into infinite chains along the b axis with graph-set motif C(4), while the weaker N-H⋯S hydrogen bond combines with the previous one into an R(2) (2)(8) network. Moreover, the chains are linked into layers parallel to (102) by weak N-H⋯F hydrogen bonds, which form an R(2) (2)(22) ring motif. In addition, there are also weak π-π inter-actions between the benzene rings of adjacent mol-ecules [centroid-centroid distance = 3.8997 (15) Å].

[The potential mechanism on signal transduction pathway in regulation of mRNA expression of high mobility group box-1 protein in septic rats].

OBJECTIVE: To investigate the potential role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in regulation of gene expression of high mobility group box-1 protein (HMGB1) in various tissues in rats with sepsis. METHODS: A sepsis model reproduced by cecal ligation and puncture (CLP), and 128 male Wistar rats were randomly divided into normal control group (n = 10), sham operation group (n = 10), CLP group (n = 60), AG490 treatment group (n = 24), and rapamycin (RPM) treatment group (n = 24). At serial time points animals in each group were sacrificed after CLP, then tissue samples were harvested to determine HMGB1 mRNA expression and STAT1/3 DNA binding activity. RESULTS: STAT1 activities increased rapidly in the liver, lungs and small intestine after CLP, peaking at 6 - 12 h, while it increased slowly, and still kept at mild level from 2 to 48 h in the kidneys. Compared with STAT1, lower STAT3 activities were detected only in the liver and lungs, with negative detection in the small intestine and kidneys. HMGB1 mRNA levels significantly increased in liver, lungs and small intestine at various time points after CLP respectively (P < 0.05 or P < 0.01), while they didn't change in the kidneys. Treatment with AG490 could markedly inhibit HMGB1 mRNA expression in the liver and small intestine at 24 and 48 h (P < 0.05 or P < 0.01), and in lungs at 2 h following CLP (P < 0.01). Similarly, treatment with RPM significantly decreased HMGB1 mRNA expression in the lungs at 2, 6, 24 and 48 h, in the liver at 6 and 24 h, and in the small intestine at 24 and 48 h (P < 0.05 or P < 0.01). In addition, STAT1 and STAT3 activities in the liver and lungs were significantly correlated with corresponding tissue HMGB1 mRNA expression. CONCLUSIONS: Peritoneal infection could extensively activate STAT1 and limitedly activate STAT3 in vital organs. Activation of JAK/STAT pathway might be involved in up-regulating the gene expression of HMGB1 and systemic inflammation secondary to severe septic challenge.

Mitochondrial accumulation in the distal part of the initial segment of chicken spinal motoneurons.

The axonal initial segment is the initiation site of action potentials and is characterized morphologically by a dense undercoating and fascicles of microtubules connected by cross-bridges. In order to analyze subcellular structures in the initial segment, we made serial transverse sections of initial segments of identified chicken motoneurons by retrograde transport of horseradish peroxidase (HRP) injected into the muscle. The mean (+/-SD) length of the initial segment was 28.1+/-2.3 microm (n=6). Mitochondria accumulated in the distal part of the initial segment, which was 1.4-6.9 microm in length (5-23% of the total length of the initial segment). In the transverse section of the distal part, mitochondrial density was 15.8+/-6.2% (n=5), while in the middle and proximal parts it was 6.1+/-1.6% and 5.6+/-1.4%, respectively. Mitochondrial accumulation was observed in common in phasic and tonic motoneurons in the chicken, and also observed in the distal part of the initial segment of the large ventral horn neurons of the chicken without HRP injection. These findings suggest that accumulated mitochondria play an important role in maintaining the physiological function of the distal part of the motoneuron initial segment.