Enzymatically inactive OGG1 binds to DNA and steers base excision repair toward gene transcription.

8-Oxoguanine DNA glycosylase1 (OGG1)-initiated base excision repair (BER) is the primary pathway to remove the pre-mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Recent studies documented 8-oxoG serves as an epigenetic-like mark and OGG1 modulates gene expression in oxidatively stressed cells. For this new role of OGG1, two distinct mechanisms have been proposed: one is coupled to base excision, while the other only requires substrate binding of OGG1--both resulting in conformational adjustment in the adjacent DNA sequences providing access for transcription factors to their cis-elements. The present study aimed to examine if BER activity of OGG1 is required for pro-inflammatory gene expression. To this end, Ogg1/OGG1 knockout/depleted cells were transfected with constructs expressing wild-type (wt) and repair-deficient mutants of OGG1. OGG1's promoter enrichment, oxidative state, and gene expression were examined. Results showed that TNFα exposure increased levels of oxidatively modified cysteine(s) of wt OGG1 without impairing its association with promoter and facilitated gene expression. The excision deficient K249Q mutant was even a more potent activator of gene expression; whereas, mutant OGG1 with impaired substrate recognition/binding was not. These data suggested the interaction of OGG1 with its substrate at regulatory regions followed by conformational adjustment in the adjacent DNA is the primary mode to modulate inflammatory gene expression.

Ultrasonographic Thyroid Nodule Classification Using a Deep Convolutional Neural Network with Surgical Pathology.

Ultrasonography with fine-needle aspiration biopsy is commonly used to detect thyroid cancer. However, thyroid ultrasonography is prone to subjective interpretations and interobserver variabilities. The objective of this study was to develop a thyroid nodule classification system for ultrasonography using convolutional neural networks. Transverse and longitudinal ultrasonographic thyroid images of 762 patients were used to create a deep learning model. After surgical biopsy, 325 cases were confirmed to be benign and 437 cases were confirmed to be papillary thyroid carcinoma. Image annotation marks were removed, and missing regions were recovered using neighboring parenchyme. To reduce overfitting of the deep learning model, we applied data augmentation, global average pooling. And 4-fold cross-validation was performed to detect overfitting. We employed a transfer learning method with the pretrained deep learning model VGG16. The average area under the curve of the model was 0.916, and its specificity and sensitivity were 0.70 and 0.92, respectively. Positive and negative predictive values were 0.90 and 0.75, respectively. We introduced a new fine-tuned deep learning model for classifying thyroid nodules in ultrasonography. We expect that this model will help physicians diagnose thyroid nodules with ultrasonography.

The Influence of Non-Linear Frequency Compression on the Perception of Speech and Music in Patients with High Frequency Hearing Loss.

BACKGROUND AND OBJECTIVES: Non-linear frequency compression (NLFC) technology compresses and shifts higher frequencies into a lower frequency area that has better residual hearing. Because consonants are uttered in the high-frequency area, NLFC could provide better speech understanding. The aim of this study was to investigate the clinical effectiveness of NLFC technology on the perception of speech and music in patients with high-frequency hearing loss. SUBJECTS AND METHODS: Twelve participants with high-frequency hearing loss were tested in a counter-balanced order, and had two weeks of daily experience with NLFC set on/off prior to testing. Performance was repeatedly evaluated with consonant tests in quiet and noise environments, speech perception in noise, music perception and acceptableness of sound quality rating tasks. Additionally, two questionnaires (the Abbreviated Profile of Hearing Aid Benefit and the Korean version of the International Outcome Inventory-Hearing Aids) were administered. RESULTS: Consonant and speech perception improved with hearing aids (NLFC on/off conditions), but there was no significant difference between NLFC on and off states. Music perception performances revealed no notable difference among unaided and NLFC on and off states. The benefits and satisfaction ratings between NLFC on and off conditions were also not significantly different, based on questionnaires, however great individual variability preferences were noted. CONCLUSIONS: Speech perception as well as music perception both in quiet and noise environments was similar between NLFC on and off states, indicating that real world benefits from NLFC technology may be limited in Korean adult hearing aid users.

Effect of structural design on the pullout strength of suture anchors for rotator cuff repair.

Various types of suture anchor designs are currently available for rotator cuff repair. The purpose of our study was to investigate the pullout strength of such anchors based on their structural design and the predominant geometric design factors affecting the pullout strength using finite element analysis. Finite element models were constructed using five cadaveric humeri and ten suture anchors with different designs. The pullout strength and distribution of bone stress around the anchor at three different directions of the applied force (0°, 45°, and 75°) were analyzed. The following geometric factors of suture anchor design were computed and their correlations with pullout strength assessed: Overall length, minor, and major diameters; number of threads; height of thread; distance between threads; helix angle; contact surface area between the anchor threads and surrounding bone; contact surface area between the cylindrical portion of the anchor; and surrounding bone and total contact surface area between the anchor and surrounding bone. The pullout strength and distribution of bone stress around the anchor varied according to the suture anchor designs and the direction of the applied force, respectively. The pullout strength had a strong positive correlation with the contact surface area between the anchor threads and surrounding bone, overall length, and the number and height of threads. This study demonstrated that suture anchor designs with increased contact surface area between the anchor threads and surrounding bone, overall length, and the number and height of threads can enhance the pullout strength during rotator cuff repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3318-3327, 2018.