Introduction
We developed a machine learning model to predict whether or not a cochlear implant (CI) candidate will develop effective language skills within 2 years after the CI surgery by using the ...pre‐implant brain fMRI data from the candidate.
Methods
The language performance was measured 2 years after the CI surgery by the Clinical Evaluation of Language Fundamentals‐Preschool, Second Edition (CELF‐P2). Based on the CELF‐P2 scores, the CI recipients were designated as either effective or ineffective CI users. For feature extraction from the fMRI data, we constructed contrast maps using the general linear model, and then utilized the Bag‐of‐Words (BoW) approach that we previously published to convert the contrast maps into feature vectors. We trained both supervised models and semi‐supervised models to classify CI users as effective or ineffective.
Results
Compared with the conventional feature extraction approach, which used each single voxel as a feature, our BoW approach gave rise to much better performance for the classification of effective versus ineffective CI users. The semi‐supervised model with the feature set extracted by the BoW approach from the contrast of speech versus silence achieved a leave‐one‐out cross‐validation AUC as high as 0.97. Recursive feature elimination unexpectedly revealed that two features were sufficient to provide highly accurate classification of effective versus ineffective CI users based on our current dataset.
Conclusion
We have validated the hypothesis that pre‐implant cortical activation patterns revealed by fMRI during infancy correlate with language performance 2 years after cochlear implantation. The two brain regions highlighted by our classifier are potential biomarkers for the prediction of CI outcomes. Our study also demonstrated the superiority of the semi‐supervised model over the supervised model. It is always worthwhile to try a semi‐supervised model when unlabeled data are available.
We developed a machine learning model to predict cochlear implant (CI) outcomes by using the pre‐implant brain fMRI data from the CI candidates. Our semi‐supervised model achieved a leave‐one‐out cross‐validation AUC as high as 0.97. Two brain regions were highlighted as potential biomarkers for the prediction of CI outcomes.
The trends in cochlear implantation candidacy and benefit have changed rapidly in the last two decades. It is now widely accepted that early implantation leads to better postimplant outcomes. ...Although some generalizations can be made about postimplant auditory and language performance, neural mechanisms need to be studied to predict individual prognosis.
The aim of this study was to use functional magnetic resonance imaging (fMRI) to identify preimplant neuroimaging biomarkers that predict children's postimplant auditory and language outcomes as measured by parental observation/reports.
This is a pre-post correlational measures study.
Twelve possible cochlear implant candidates with bilateral severe to profound hearing loss were recruited via referrals for a clinical magnetic resonance imaging to ensure structural integrity of the auditory nerve for implantation.
Participants underwent cochlear implantation at a mean age of 19.4 mo. All children used the advanced combination encoder strategy (ACE, Cochlear Corporation™, Nucleus
Freedom cochlear implants). Three participants received an implant in the right ear; one in the left ear whereas eight participants received bilateral implants. Participants' preimplant neuronal activation in response to two auditory stimuli was studied using an event-related fMRI method.
Blood oxygen level dependent contrast maps were calculated for speech and noise stimuli. The general linear model was used to create z-maps. The Auditory Skills Checklist (ASC) and the SKI-HI Language Development Scale (SKI-HI LDS) were administered to the parents 2 yr after implantation. A nonparametric correlation analysis was implemented between preimplant fMRI activation and postimplant auditory and language outcomes based on ASC and SKI-HI LDS. Statistical Parametric Mapping software was used to create regression maps between fMRI activation and scores on the aforementioned tests. Regression maps were overlaid on the Imaging Research Center infant template and visualized in MRIcro.
Regression maps revealed two clusters of brain activation for the speech versus silence contrast and five clusters for the noise versus silence contrast that were significantly correlated with the parental reports. These clusters included auditory and extra-auditory regions such as the middle temporal gyrus, supramarginal gyrus, precuneus, cingulate gyrus, middle frontal gyrus, subgyral, and middle occipital gyrus. Both positive and negative correlations were observed. Correlation values for the different clusters ranged from -0.90 to 0.95 and were significant at a corrected p value of <0.05. Correlations suggest that postimplant performance may be predicted by activation in specific brain regions.
The results of the present study suggest that (1) fMRI can be used to identify neuroimaging biomarkers of auditory and language performance before implantation and (2) activation in certain brain regions may be predictive of postimplant auditory and language performance as measured by parental observation/reports.
Patterning along the anterior-posterior (A-P) axis in Drosophila embryos is instructed by the morphogen gradient of Bicoid (Bcd). Despite extensive studies of this morphogen, how embryo geometry may ...affect gradient formation and target responses has not been investigated experimentally.
In this report, we systematically compare the Bcd gradient profiles and its target expression patterns on the dorsal and ventral sides of the embryo. Our results support a hypothesis that proper distance measurement and the encoded positional information of the Bcd gradient are along the perimeter of the embryo. Our results also reveal that the dorsal and ventral sides of the embryo have a fundamentally similar relationship between Bcd and its target Hunchback (Hb), suggesting that Hb expression properties on the two sides of the embryo can be directly traced to Bcd gradient properties. Our 3-D simulation studies show that a curvature difference between the two sides of an embryo is sufficient to generate Bcd gradient properties that are consistent with experimental observations.
The findings described in this report provide a first quantitative, experimental evaluation of embryo geometry on Bcd gradient formation and target responses. They demonstrate that the physical features of an embryo, such as its shape, are integral to how pattern is formed.
STUDY QUESTION
Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?
SUMMARY ANSWER
Many genetic variants influencing age at ...menarche in European populations appear to impact Chinese populations in a similar manner.
WHAT IS KNOWN AND WHAT THIS PAPER ADDS
Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women.
PARTICIPANTS AND SETTING
We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche.
MAIN RESULTS
For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10−6, binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile.
BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS
Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results.
STUDY FUNDING/COMPETING INTERESTS
This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.
Abstract
Single-line spectroscopic binaries have recently contributed to stellar-mass black hole discovery, independently of the X-ray transient method. We report the identification of a single-line ...binary system, LTD064402+245919, with an orbital period of 14.50 days. The observed component is a subgiant with a mass of 2.77 ± 0.68
M
⊙
, radius 15.5 ± 2.5
R
⊙
, effective temperature
T
eff
4500 ± 200 K, and surface gravity log
g
2.5 ± 0.25 dex. The discovery makes use of the Large Sky Area Multi-Object fiber Spectroscopic Telescope time-domain and Zwicky Transient Facility survey. Our general-purpose software pipeline applies a Lomb–Scargle periodogram to determine the orbital period and uses machine learning to classify the variable type from the folded light curves. We apply a combined model to estimate the orbital parameters from both the light and radial velocity curves, taking constraints on the primary star mass, mass function, and detection limit of secondary luminosity into consideration. We obtain a radial velocity semiamplitude of 44.6 ± 1.5 km s
−1
, mass ratio of 0.73 ± 0.07, and an undetected component mass of 2.02 ± 0.49
M
⊙
when the type of the undetected component is not set. We conclude that the inclination is not well constrained, and that the secondary mass is larger than 1
M
⊙
when the undetected component is modeled as a compact object. According to our investigations using a Monte Carlo Markov Chain simulation, increasing the spectra signal-to-noise ratio by a factor of 3 would enable the secondary light to be distinguished (if present). The algorithm and software in this work are able to serve as general-purpose tools for the identification of compact objects quiescent in X-rays.
Expanded polyglutamine (polyQ) tract in the human TATA-box-binding protein (hTBP) causes the neurodegenerative disease spinocerebellar ataxia 17 (SCA17). To investigate the pathological effects of ...polyQ expansion, we established a SCA17 model in Drosophila. Similar to SCA17 patients, transgenic flies expressing a mutant hTBP protein with an expanded polyQ tract (hTBP80Q) exhibit progressive neurodegeneration, late-onset locomotor impairment and shortened lifespan. Microarray analysis reveals that hTBP80Q causes widespread and time-dependent transcriptional dysregulation in Drosophila. In a candidate screen for genetic modifiers, we identified RBP-J/Su(H), a transcription factor that contains Q/N-rich domains and participates in Notch signaling. Knockdown of Su(H) by RNAi further enhances hTBP80Q-induced eye defects, whereas overexpression of Su(H) suppresses such defects. While the Su(H) transcript level is not significantly altered in hTBP80Q-expressing flies, genes that contain Su(H)-binding sites are among those that are dysregulated. We further show that hTBP80Q interacts more efficiently with Su(H) than wild-type hTBP, suggesting that a reduction in the fraction of Su(H) available for its normal cellular functions contributes to hTBP80Q-induced phenotypes. While the Notch signaling pathway has been implicated in several neurological disorders, our study suggests a possibility that the activity of its nuclear component RBP-J/Su(H) may modulate the pathological progression in SCA17 patients.
Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified ...associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at
< 2.61 × 10
, a Bonferroni-corrected threshold, including nine genes that remained significant at
< 2.61 × 10
after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. SIGNIFICANCE: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
Objective
The present study examined the impact of expressive writing on reducing posttraumatic stress disorder symptoms (PTSS) and facilitating posttraumatic growth (PTG) in Chinese American breast ...cancer survivors.
Method
Ninety‐six women who had completed primary treatments for breast cancer were randomly assigned to a cancer experience facts condition, an emotional disclosure condition, or a self‐regulation condition and wrote on three occasions over 3 weeks. Participants completed outcome assessments at baseline and 1, 3, and 6 months after the last writing session.
Results
Surprisingly, results indicated that there was generally a small increase in PTSS (ESsg = .16) and a small decrease in PTG (ESsg = −.16) from baseline to the 6‐month follow‐up. Effect size comparisons and latent growth curve models also indicated that the cancer facts condition was generally associated with superior outcomes for both PTSS and PTG.
Conclusions
These findings speak to the importance of examining whether interventions are equally efficacious in different cultures.
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