The sexual brain,genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (p _fdr < .001, ηp2 = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) (p _fdr < .001, ηp2 < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.     

Enhanced dissolution of sildenafil citrate as dry foam tablets

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.     

Voice outcomes of polyacrylamide hydrogel injection laryngoplasty

OBJECTIVES: Polyacrylamide hydrogel (PAAG, Aquamid) is widely used as permanent facial tissue filler during facial plastic surgery. In this study, we examined the long-term effects and safety aspects of PAAG as a vocal fold augmentation material for patients with permanent unilateral vocal cord paralysis. STUDY DESIGN: Prospective clinical trials. METHODS: PAAG injection laryngoplasty was performed in 34 consecutive patients with permanent unilateral vocal cord paralysis. Percutaneous injection was performed under local anesthesia into the vocalis muscle using disposable 25 gauge long needles. Of the 34 patients, 16 completed acoustic, perceptual, stroboscopic, and subjective evaluations prior to the injection and at 6 and 12 months after the injection. RESULTS: Acoustic and perceptual parameters (GRBAS [Overall grade of dysphonia, Roughness, Breathiness, Aesthenia, Strain], Maximal phonation time [MPT], jitter, and shimmer) were significantly improved (P < .05) after injection and remained stable over 12 months. The grades of mucosal waves and glottic closure were also significantly improved (P < .01). The voice handicap index (VHI), as well as the visual analogue scale (VAS) of hoarseness and aspiration significantly improved over 12 months. No adverse effects were observed except for a decrease in the mucosal wave of one patient, after injection into a superficial area of the vocal fold. CONCLUSION: Based on the preliminary results of this trial, PAAG appears to be a long-lasting and safe injection material that is suitable for the treatment of glottal insufficiency caused by permanent unilateral vocal cord paralysis.     

Nanoscale mapping of temperature-dependent conduction in an epitaxial VO2 film grown on an Al2O3 substrate

Vanadium dioxide (VO₂) is one of the extensively studied strongly correlated oxides due to its intriguing insulator–metal transition near room temperature. In this work, we investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy (C-AFM). We observed that only the regions near the grain boundaries are conductive, producing intriguing donut patterns in C-AFM images. Such donut patterns were observed in the entire measured temperature range (300–355 K). The current values near the grain boundaries increased by approximately two orders of magnitude with an increase in the temperature, which is consistent with the macroscopic transport data. The spatially-varied conduction behavior is ascribed to the coexistence of different monoclinic phases, i.e., M1 and M2 phases, based on the results of temperature-dependent Raman spectroscopy. Furthermore, we investigated the conduction mechanism in the relatively conductive M1 phase regions at room temperature using current–voltage (I–V) spectroscopy and deep data analysis. Bayesian linear unmixing and k-means clustering showed three distinct types of conduction behavior, which classical C-AFM cannot resolve. We found that the conduction in the M1 phase regions can be explained by the Poole–Frenkel mechanism. This work provides deep insight into IMT behavior in the epitaxial VO₂ thin film at the nanoscale, especially the coexistence and evolution of the M1 and M2 phases. This work also highlights that I–V spectroscopy combined with deep data analysis is very powerful in investigating local transport in complex oxides and various material systems.

We investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy and deep data analysis.