Are Smartwatches a Suitable Tool to Monitor Noise Exposure for Public Health Awareness and Otoprotection?

Introduction and Objectives: Noise-induced hearing loss (NIHL) and tinnitus are common problems that can be prevented with hearing protection measures. Sound level meters and noise dosimeters enable to monitor and identify health-threatening occupational or recreational noise, but are limited in their daily application because they are usually difficult to operate, bulky, and expensive. Smartwatches, which are becoming increasingly available and popular, could be a valuable alternative to professional systems. Therefore, the aim of this study was to evaluate the applicability of smartwatches for accurate environmental noise monitoring. Methods: The A-weighted equivalent continuous sound pressure level (LAeq) was recorded and compared between a professional sound level meter and a popular smartwatch. Noise exposure was assessed in 13 occupational and recreational settings, covering a large range of sound pressure levels between 35 and 110 dBA. To assess measurement agreement, a Bland-Altman plot, linear regression, the intra-class correlation coefficient, and descriptive statistics were used. Results: Overall, the smartwatch underestimated the sound level meter measurements by 0.5 dBA (95% confidence interval [0.2, 0.8]). The intra-class correlation coefficient showed excellent agreement between the two devices (ICC = 0.99), ranging from 0.65 (music club) to 0.99 (concert) across settings. The smartwatch’s sampling rate decreased significantly with lower sound pressure levels, which could have introduced measurement inaccuracies in dynamic acoustic environments. Conclusions: The assessment of ambient noise with the tested smartwatch is sufficiently accurate and reliable to improve awareness of hazardous noise levels in the personal environment and to conduct exploratory clinical research. For professional and legally binding measurements, we recommend specialized sound level meters or noise dosimeters. In the future, smartwatches will play an important role in monitoring personal noise exposure and will provide a widely available and cost-effective measure for otoprotection

Cochlear implant electrode impedance subcomponents as biomarker for residual hearing.

INTRODUCTION AND OBJECTIVES Maintaining the structural integrity of the cochlea and preserving residual hearing is crucial for patients, especially for those for whom electric acoustic stimulation is intended. Impedances could reflect trauma due to electrode array insertion and therefore could serve as a biomarker for residual hearing. The aim of this study is to evaluate the association between residual hearing and estimated impedance subcomponents in a known collective from an exploratory study. METHODS A total of 42 patients with lateral wall electrode arrays from the same manufacturer were included in the study. For each patient, we used data from audiological measurements to compute residual hearing, impedance telemetry recordings to estimate near and far-field impedances using an approximation model, and computed tomography scans to extract anatomical information about the cochlea. We assessed the association between residual hearing and impedance subcomponent data using linear mixed-effects models. RESULTS The progression of impedance subcomponents showed that far-field impedance was stable over time compared to near-field impedance. Low-frequency residual hearing demonstrated the progressive nature of hearing loss, with 48% of patients showing full or partial hearing preservation after 6 months of follow-up. Analysis revealed a statistically significant negative effect of near-field impedance on residual hearing (-3.81 dB HL per kΩ; p < 0.001). No significant effect of far-field impedance was found. CONCLUSION Our findings suggest that near-field impedance offers higher specificity for residual hearing monitoring, while far-field impedance was not significantly associated with residual hearing. These results highlight the potential of impedance subcomponents as objective biomarkers for outcome monitoring in cochlear implantation

Efficient treatment of three-body interactions in transcorrelated methods

An efficient implementation for approximate inclusion of the three-body operator arising in transcorrelated methods via exclusion of explit three body correlation (xTC) is presented and tested against results in the ``HEAT'' benchmark set [A. Tajti et al., J. Chem. Phys. 121, 11599 (2004)]. Using relatively modest basis sets and computationally simple methods, total, atomization, and formation energies within near-chemical accuracy from HEAT results were obtained. The xTC ansatz reduces the nominal scaling of the three-body part of transcorrelation by two orders of magnitude to O(N^5) and can readily be used with almost any quantum chemical correlation method

Postoperative Impedance-Based Estimation of Cochlear Implant Electrode Insertion Depth.

OBJECTIVES Reliable determination of cochlear implant electrode positions shows promise for clinical applications, including anatomy-based fitting of audio processors or monitoring of electrode migration during follow-up. Currently, electrode positioning is measured using radiography. The primary objective of this study is to extend and validate an impedance-based method for estimating electrode insertion depths, which could serve as a radiation-free and cost-effective alternative to radiography. The secondary objective is to evaluate the reliability of the estimation method in the postoperative follow-up over several months. DESIGN The ground truth insertion depths were measured from postoperative computed tomography scans obtained from the records of 56 cases with an identical lateral wall electrode array. For each of these cases, impedance telemetry records were retrieved starting from the day of implantation up to a maximum observation period of 60 mo. Based on these recordings, the linear and angular electrode insertion depths were estimated using a phenomenological model. The estimates obtained were compared with the ground truth values to calculate the accuracy of the model. RESULTS Analysis of the long-term recordings using a linear mixed-effects model showed that postoperative tissue resistances remained stable throughout the follow-up period, except for the two most basal electrodes, which increased significantly over time (electrode 11: ~10 Ω/year, electrode 12: ~30 Ω/year). Inferred phenomenological models from early and late impedance telemetry recordings were not different. The insertion depth of all electrodes was estimated with an absolute error of 0.9 mm ± 0.6 mm or 22° ± 18° angle (mean ± SD). CONCLUSIONS Insertion depth estimations of the model were reliable over time when comparing two postoperative computed tomography scans of the same ear. Our results confirm that the impedance-based position estimation method can be applied to postoperative impedance telemetry recordings. Future work needs to address extracochlear electrode detection to increase the performance of the method

A three-microRNA signature identifies two subtypes of glioblastoma patients with different clinical outcomes

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults, characterized by aggressive growth, limited response to therapy, and inexorable recurrence. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant patient stratification systems. Analyzing a collection of patient-derived GBM stem-like cells (GSCs) by gene expression profiling, nuclear magnetic resonance (NMR) spectroscopy and signal transduction pathway activation, we identified two GSC clusters characterized by different clinical features. Due to the widely documented role played by microRNAs (miRNAs) in the tumorigenesis process, in this study we explored whether these two GBM patient subtypes could also be discriminated by different miRNA signatures. Global miRNA expression pattern was analyzed by oblique principal component (OPC) analysis and principal component analysis (PCA). By a combined inferential strategy on PCA results, we identified a reduced set of three miRNAs - miR-23a, miR-27a and miR-9* (miR-9-3p) - able to discriminate the proneural- and mesenchymal-like GSC phenotypes as well as mesenchymal and proneural subtypes of primary GBM included in The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis showed a significant correlation between the selected miRNAs and overall survival in 429 GBM specimens from TCGA-identifying patients who had an unfavorable outcome. The survival prognostic capability of the three miRNA signatures could have important implications for the understanding of the biology of GBM subtypes and could be useful in patient stratification to facilitate interpretation of results from clinical trials

TGF-ß induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression.

Abstract TGF-ß/Activin induces epithelial-to-mesenchymal transition (EMT) and stemness in pancreatic ductal adenocarcinoma (PDAC). However, the microRNAs (miRNAs) regulated during this response have remained yet undetermined. Here, we show that TGF-ß transcriptionally induces MIR100HG lncRNA, containing miR-100, miR-125b and let-7a in its intron, via SMAD2/3. Interestingly, we find that although the pro-tumourigenic miR-100 and miR-125b accordingly increase, the amount of anti-tumourigenic let-7a is unchanged, as TGF-ß also induces LIN28B inhibiting its maturation. Notably, we demonstrate that inactivation of miR-125b or miR-100 affects the TGF-ß-mediated response indicating that these miRNAs are important TGF-ß effectors. We integrated AGO2-RIP-seq with RNA-seq to identify the global regulation exerted by these miRNAs in PDAC cells. Transcripts targeted by miR-125b and miR-100 significantly overlap and mainly inhibit p53 and cell-cell junctions’ pathways. Together, we uncover that TGF-ß induces an lncRNA, whose encoded miRNAs, miR-100, let-7a and miR-125b, play opposing roles in controlling PDAC tumourigenesis

A network of assembly factors is involved in remodeling rRNA elements during preribosome maturation

The following corrections appear in the attached pdf labelled "Correction to Version of Record". The authors inadvertently omitted Woonghee Lee from the list of authors. The corrected author list and affiliations are noted. Revised acknowledgment paragraphs including Woonghee Lee’s funding source and contribution also appear in the correction. In addition, the authors noted the omission of details of NMR structure calculation from the Materials and Methods section. The relevant paragraph and the references associated with it are appended.Eukaryotic ribosome biogenesis involves ∼200 assembly factors, but how these contribute to ribosome maturation is poorly understood. Here, we identify a network of factors on the nascent 60S subunit that actively remodels preribosome structure. At its hub is Rsa4, a direct substrate of the force-generating ATPase Rea1. We show that Rsa4 is connected to the central protuberance by binding to Rpl5 and to ribosomal RNA (rRNA) helix 89 of the nascent peptidyl transferase center (PTC) through Nsa2. Importantly, Nsa2 binds to helix 89 before relocation of helix 89 to the PTC. Structure-based mutations of these factors reveal the functional importance of their interactions for ribosome assembly. Thus, Rsa4 is held tightly in the preribosome and can serve as a “distribution box,” transmitting remodeling energy from Rea1 into the developing ribosome. We suggest that a relay-like factor network coupled to a mechano-enzyme is strategically positioned to relocate rRNA elements during ribosome maturation

MicroRNA-9 as Potential Biomarker for Breast Cancer Local Recurrence and Tumor Estrogen Receptor Status

MicroRNAs (miRs) are small, non-protein coding transcripts involved in many cellular functions. Many miRs have emerged as important cancer biomarkers. In the present study, we investigated whether miR levels in breast tumors are predictive of breast cancer local recurrence (LR). Sixty-eight women who were diagnosed with breast cancer at the Lombardi Comprehensive Cancer Center were included in this study. Breast cancer patients with LR and those without LR were matched on year of surgery, age at diagnosis, and type of surgery. Candidate miRs were identified by screening the expression levels of 754 human miRs using miR arrays in 16 breast tumor samples from 8 cases with LR and 8 cases without LR. Eight candidate miRs that showed significant differences between tumors with and without LR were further verified in 52 tumor samples using real-time PCR. Higher expression of miR-9 was significantly associated with breast cancer LR in all cases as well as the subset of estrogen receptor (ER) positive cases (p = 0.02). The AUCs (Area Under Curve) of receiver operating characteristic (ROC) curves of miR-9 for all tumors and ER positive tumors are 0.68 (p = 0.02) and 0.69 (p = 0.02), respectively. In ER positive cases, Kaplan-Meier analysis showed that patients with lower miR-9 levels had significantly better 10-year LR-free survival (67.9% vs 30.8%, p = 0.02). Expression levels of miR-9 and another miR candidate, miR-375, were also strongly associated with ER status (p<0.001 for both). The potential of miR-9 as a biomarker for LR warrants further investigation with larger sample size

Design, construction, and functional characterization of a tRNA neochromosome in yeast

Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the ∼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs