Generalizable Deep Learning-based Sleep Staging Approach for Ambulatory Textile Electrode Headband Recordings.

Reliable, automated, and user-friendly solutions for the identification of sleep stages in home environment are needed in various clinical and scientific research settings. Previously we have shown that signals recorded with an easily applicable textile electrode headband (FocusBand, T 2 Green Pty Ltd) contain characteristics similar to the standard electrooculography (EOG, E1-M2). We hypothesize that the electroencephalographic (EEG) signals recorded using the textile electrode headband are similar enough with standard EOG in order to develop an automatic neural network-based sleep staging method that generalizes from diagnostic polysomnographic (PSG) data to ambulatory sleep recordings of textile electrode-based forehead EEG. Standard EOG signals together with manually annotated sleep stages from clinical PSG dataset (n = 876) were used to train, validate, and test a fully convolutional neural network (CNN). Furthermore, ambulatory sleep recordings including a standard set of gel-based electrodes and the textile electrode headband were conducted for 10 healthy volunteers at their homes to test the generalizability of the model. In the test set (n = 88) of the clinical dataset, the model's accuracy for 5-stage sleep stage classification was 80% (κ = 0.73) using only the single-channel EOG. The model generalized well for the headband-data, reaching 82% (κ = 0.75) overall sleep staging accuracy. In comparison, accuracy of the model was 87% (κ = 0.82) in home recordings using the standard EOG. In conclusion, the CNN model shows potential on automatic sleep staging of healthy individuals using a reusable electrode headband in a home environment.

Total durations of respiratory events are modulated within REM and NREM sleep by sleeping position and obesity in OSA patients.

BACKGROUND: Supine sleeping position and obesity are well-known risk factors for obstructive sleep apnea (OSA) and modulate the risk for OSA-related daytime symptoms. Although respiratory event durations are associated with OSA-related severe health consequences, it is unclear how sleeping position, obesity, and daytime sleepiness are associated with respiratory event durations during REM and NREM sleep. We hypothesize that irrespective of the apnea-hypopnea index (AHI), respiratory event durations differ significantly between various OSA subgroups during REM and NREM sleep. METHODS: One night in-lab polysomnographic recordings were retrospectively analyzed from 1910 untreated suspected OSA patients. 599 patients (AHI ≥ 5) were included in study and divided into subgroups based on positional dependency, BMI, and daytime sleepiness (Epworth Sleepiness Scale and Multiple Sleep Latency Test). Differences in total hypopnea time (THT), total apnea time (TAT), and total apnea-hypopnea time (TAHT) within REM and NREM sleep between the subgroups were evaluated. RESULTS: During REM sleep, positional OSA patients had lower THT (OR = 0.952, p < 0.001) and TAHT (OR = 0.943, p < 0.001) than their non-positional counterparts. Compared to normal-weight patients (BMI < 25 kg/m2), obese patients (BMI ≥ 30 kg/m2) had lower THT, TAT, and TAHT (ORs = 0.942-0.971, p ≤ 0.009) during NREM sleep but higher THT (OR = 1.057, p = 0.001) and TAHT (OR = 1.052, p = 0.001) during REM sleep. No significant differences were observed in THT, TAT, and TAHT between patients with and without daytime sleepiness. CONCLUSION: Regardless of the AHI, respiratory event durations vary significantly between OSA sub-groups during REM and NREM sleep. Therefore, to personalize OSA severity estimation the diagnosis should be tailored based on patient's demographics, clinical phenotype, and PSG characteristics.

Polysomnographic characteristics of severe obstructive sleep apnea vary significantly between hypertensive and normotensive patients of both genders.

PURPOSE: Hypertension is a common finding in patients with obstructive sleep apnea (OSA), but it has remained unclear whether or not the amount of disturbed breathing and characteristics of individual respiratory events differ between hypertensive and normotensive patients with severe OSA. METHODS: Full polysomnographic recordings of 323 men and 89 women with severe OSA were analyzed. Differences in the duration of individual respiratory events, total apnea and hypopnea times, and the percentage of disturbed breathing from total sleep time (AHT%) were compared between normotensive and hypertensive patients separately by genders. Furthermore, differences in the respiratory event characteristics were assessed between three AHT% groups (AHT% ≤ 30%, 30% < AHT% ≤ 45%, and AHT% > 45%). RESULTS: Hypertensive women had lower percentage apnea time (15.2% vs. 18.2%, p = 0.003) and AHT% (33.5% vs. 36.5%, p = 0.021) when compared with normotensive women. However, these differences were not observed between hypertensive and normotensive men. Percentage hypopnea time was higher in hypertensive men (13.5% vs. 11.2%, p = 0.043) but not in women (15.2% vs. 12.2%, p = 0.130) compared with their normotensive counterparts. The variation in AHI explained 60.5% (ρ = 0.778) and 65.0% (ρ = 0.806) of the variation in AHT% in normotensive and hypertensive patients, respectively. However, when AHT% increased, the capability of AHI to explain the variation in AHT% declined. CONCLUSIONS: There is a major inter- and intra-gender variation in percentage apnea and hypopnea times between hypertensive and normotensive patients with severe OSA. OSA is an important risk factor for hypertension and thus, early detection and phenotyping of OSA would allow timely treatment of patients with the highest risk of hypertension.

Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases.

Metabolomics is a systemic study of metabolites, which are small molecules generated by the process of metabolism. The metabolic profile of saliva can provide an early outlook of the changes associated with a wide range of diseases, including oral cancer and periodontal diseases. It is possible to measure levels of disease-specific metabolites using different methods as presented in this study. However, many challenges exist including incomplete understanding of the complicated metabolic pathways of different oral diseases. The review concludes with the discussion on future perspectives of salivary metabolomics from a clinician point of view. Salivary metabolomics may afford a new research avenue to identify local and systemic disorders but also to aid in the design and modification of therapies. A MEDLINE search using keywords "salivary metabolomics" returned 23 results in total, of which seven were omitted for being reviews or letters to the editor. The rest of the articles were used for preparation of the review, 13 of these were published in the last 5 years.

Immunoneutralization of growth differentiation factor 9 reveals it partially accounts for mouse oocyte mitogenic activity.

Paracrine factors secreted by oocytes play a pivotal role in promoting early ovarian follicle growth and in defining a morphogenic gradient in antral follicles, yet the exact identities of these oocyte factors remain unknown. This study was conducted to determine the extent to which the mitogenic activity of mouse oocytes can be attributed to growth differentiation factor 9 (GDF9). To do this, specific anti-human GDF9 monoclonal antibodies were generated. Based on epitope mapping and bioassays, a GDF9 neutralizing antibody, mAb-GDF9-53, was characterized with very low cross-reactivity with related transforming growth factor (TGF)beta superfamily members, including BMP15 (also called GDF9B). Pep-SPOT epitope mapping showed that mAb-GDF9-53 recognizes a short 4-aa sequence, and three-dimensional peptide modeling suggested that this binding motif lies at the C-terminal fingertip of mGDF9. As predicted by sequence alignments and modeling, the antibody detected recombinant GDF9, but not BMP15 in a Western blot and GDF9 protein in oocyte extract and oocyte-conditioned medium. In a mouse mural granulosa cell (MGC) bioassay, mAb-GDF9-53 completely abolished the mitogenic effects of GDF9, but had no effect on TGFbeta1 or activin A-stimulated MGC proliferation. An unrelated IgG at the same dose had no effect on GDF9 activity. This GDF9 neutralizing antibody was then tested in an established oocyte-secreted mitogen bioassay, where denuded oocytes cocultured with granulosa cells promote cell proliferation in a dose-dependent manner. The mAb-GDF9-53 dose dependently (0-160 microg/ml) decreased the mitogenic activity of oocytes but only by approximately 45% at the maximum dose of mAb. Just 5 microg/ml of mAb-GDF9-53 neutralized 90% of recombinant mGDF9 mitogenic activity, but only 15% of oocyte activity. Unlike mAb-GDF9-53, a TGFbeta pan-specific neutralizing antibody did not affect the mitogenic capacity of the oocyte, but completely neutralized TGF beta 1-induced DNA synthesis. This study has characterized a specific GDF9 neutralizing antibody. Our data provide the first direct evidence that the endogenous GDF9 protein is an important oocyte-secreted mitogen, but also show that GDF9 accounts for only part of total oocyte bioactivity.