cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.15154/1334292
title: The topography of alpha-band activity tracks the content of spatial working memory

description: Working memory (WM) is a system for the online storage of information. An emerging view is that neuronal oscillations coordinate the cellular assemblies that code the content of WM. In line with this view, previous work has demonstrated that oscillatory activity in the alpha-band (8-12 Hz) plays a role in WM maintenance but the exact contributions of this activity have remained unclear. Here, we used an inverted spatial encoding model in combination with electroencephalography (EEG) to test whether the topographic distribution of alpha-band activity tracks spatial representations held in WM. Participants in three experiments performed spatial WM tasks that required them to remember the precise angular location of a sample stimulus for 1000-1750 ms. Across all three experiments, we found that the topographic distribution of alpha-band activity tracked the specific location that was held in WM. Evoked (i.e., activity phase-locked to stimulus onset) and total (i.e., activity regardless of phase) power across a range of low frequency-bands transiently tracked the location of the sample stimulus following stimulus onset. However, only total power in the alpha-band tracked the content of spatial WM throughout the memory delay period, which enabled reconstruction of location-selective channel tuning functions (CTFs). These findings demonstrate that alpha-band activity is directly related to the coding of spatial representations held in WM, and provide a promising method for tracking the content of this online memory system.
DOI: 10.15154/1334293
title: Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder.

description: Subject level data for associated publication
DOI: 10.15154/1334294
title: Cross-trial prediction of treatment outcome in depression: a machine learning approach

description: Background: Antidepressant treatment efficacy is low, but might be improved by matching patients to interventions. At present, clinicians have no empirically validated mechanisms to assess whether a patient with depression will respond to a specific antidepressant. We aimed to develop an algorithm to assess whether patients will achieve symptomatic remission from a 12-week course of citalopram.

Methods: We used patient-reported data from patients with depression (n=4041, with 1949 completers) from level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D; ClinicalTrials.gov, number NCT00021528) to identify variables that were most predictive of treatment outcome, and used these variables to train a machine-learning model to predict clinical remission. We externally validated the model in the escitalopram treatment group (n=151) of an independent clinical trial (Combining Medications to Enhance Depression Outcomes [COMED]; ClinicalTrials.gov, number NCT00590863).

Findings: We identified 25 variables that were most predictive of treatment outcome from 164 patient-reportable variables, and used these to train the model. The model was internally cross-validated, and predicted outcomes in the STAR*D cohort with accuracy significantly above chance (64·6% [SD 3·2]; p&lt;0·0001). The model was externally validated in the escitalopram treatment group (N=151) of COMED (accuracy 59·6%, p=0.043). The model also performed significantly above chance in a combined escitalopram-buproprion treatment group in COMED (n=134; accuracy 59·7%, p=0·023), but not in a combined venlafaxine-mirtazapine group (n=140; accuracy 51·4%, p=0·53), suggesting specificity of the model to underlying mechanisms.

Interpretation: Building statistical models by mining existing clinical trial data can enable prospective identification of patients who are likely to respond to a specific antidepressant.
DOI: 10.15154/1334299
title: The clinical relevance of self-reported premenstrual worsening of depressive symptoms in the management of depressed outpatients: a STAR*D report.

description: OBJECTIVE:
To determine the incidence, clinical and demographic correlates, and relationship to treatment outcome of self-reported premenstrual exacerbation of depressive symptoms in premenopausal women with major depressive disorder who are receiving antidepressant medication.

METHOD:
This post-hoc analysis used clinical trial data from treatment-seeking, premenopausal, adult female outpatients with major depression who were not using hormonal contraceptives. For this report, citalopram was used as the first treatment step. We also used data from the second step in which one of three new medications were used (bupropion-SR [sustained release], venlafaxine-XR [extended release], or sertraline). Treatment-blinded assessors obtained baseline treatment outcomes data. We hypothesized that those with reported premenstrual depressive symptom exacerbation would have more general medical conditions, longer index depressive episodes, lower response or remission rates, and shorter times-to-relapse with citalopram, and that they would have a better outcome with sertraline than with bupropion-SR.

RESULTS:
At baseline, 66% (n=545/821) of women reported premenstrual exacerbation. They had more general medical conditions, more anxious features, longer index episodes, and shorter times-to-relapse (41.3 to 47.1 weeks, respectively). Response and remission rates to citalopram, however, were unrelated to reported premenstrual exacerbation. Reported premenstrual exacerbation was also unrelated to differential benefit with sertraline and bupropion-SR.

CONCLUSIONS:
Self-reported premenstrual exacerbation has moderate clinical utility in the management of depressed patients, although it is not predictive of overall treatment response. Factors that contribute to a more chronic or relapsing course may also play a role in premenstrual worsening of major depressive disorder (MDD).
DOI: 10.15154/1334300
title: Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis.

description: Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an important axis of genetic heterogeneity contributing to expression variability among affected individuals has been overlooked. To this end, we develop a new gene expression analysis method-aberrant gene expression analysis, based on the multivariate distance commonly used for outlier detection. Our method detects the discrepancies in gene expression dispersion between groups and identifies genes with significantly different expression variability. Using this new method, we re-visited RNA sequencing data generated from post-mortem brain tissues of 47 ASD and 57 control samples. We identified 54 functional gene sets whose expression dispersion in ASD samples is more pronounced than that in controls, as well as 76 co-expression modules present in controls but absent in ASD samples due to ASD-specific aberrant gene expression. We also exploited aberrantly expressed genes as biomarkers for ASD diagnosis. With a whole blood expression data set, we identified three aberrantly expressed gene sets whose expression levels serve as discriminating variables achieving &gt;70 % classification accuracy. In summary, our method represents a novel discovery and diagnostic strategy for ASD. Our findings may help open an expression variability-centered research avenue for other genetically heterogeneous disorders.
DOI: 10.15154/1334312
title: Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci

description: Analysis of de novo CNVs (dnCNVs) from the full Simons Simplex Collection (SSC) (N = 2,591 families) replicates prior findings of strong association with autism spectrum disorders (ASDs) and confirms six risk loci (1q21.1, 3q29, 7q11.23, 16p11.2, 15q11.2-13, and 22q11.2). The addition of published CNV data from the Autism Genome Project (AGP) and exome sequencing data from the SSC and the Autism Sequencing Consortium (ASC) shows that genes within small de novo deletions, but not within large dnCNVs, significantly overlap the high-effect risk genes identified by sequencing. Alternatively, large dnCNVs are found likely to contain multiple modest-effect risk genes. Overall, we find strong evidence that de novo mutations are associated with ASD apart from the risk for intellectual disability. Extending the transmission and de novo association test (TADA) to include small de novo deletions reveals 71 ASD risk loci, including 6 CNV regions (noted above) and 65 risk genes (FDR ≤ 0.1).
DOI: 10.15154/1334313
title: Engineering microdeletions and microduplications by targeting segmental duplications with CRISPR.

description: Recurrent, reciprocal genomic disorders resulting from non-allelic homologous recombination (NAHR) between near-identical segmental duplications (SDs) are a major cause of human disease, often producing phenotypically distinct syndromes. The genomic architecture of flanking SDs presents a challenge for modeling these syndromes; however, the capability to efficiently generate reciprocal copy number variants (CNVs) that mimic NAHR would represent a valuable modeling tool. We describe here a CRISPR/Cas9 genome engineering method, single-guide CRISPR/Cas targeting of repetitive elements (SCORE), to model reciprocal genomic disorders and demonstrate its capabilities by generating reciprocal CNVs of 16p11.2 and 15q13.3, including alteration of one copy-equivalent of the SDs that mediate NAHR in vivo. The method is reproducible, and RNA sequencing reliably clusters transcriptional signatures from human subjects with in vivo CNVs and their corresponding in vitro models. This new approach will provide broad applicability for the study of genomic disorders and, with further development, may also permit efficient correction of these defects.
DOI: 10.15154/1334670
title: Randomized comparative efficacy study of parent-mediated intervention for toddlers with autism.

description: Subject level data for associated publication
DOI: 10.15154/1334671
title: Genomic evidence for multifactorial inheritance in autism

description: Autism spectrum disorder (ASD) is a common highly heritable disorder with multifactorial influences.
DOI: 10.15154/1336394
title: Defining the spectrum of large inversions, complex structural variation, and chromothripsis in the morbid genome.

description: Subject level data for associated publication
DOI: 10.15154/1336398
title: The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Medial Prefrontal Cortex in Autism.

description: UNASSIGNED:
The cognitive phenotype of autism has been correlated with an altered balance of excitation to inhibition in the cerebral cortex, which could result from a change in the number, function, or morphology of GABA-expressing interneurons. The number of GABAergic interneuron subtypes has not been quantified in the autistic cerebral cortex. We classified interneurons into 3 subpopulations based on expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin. We quantified the number of each interneuron subtype in postmortem neocortical tissue from 11 autistic cases and 10 control cases. Prefrontal Brodmann Areas (BA) BA46, BA47, and BA9 in autism and age-matched controls were analyzed by blinded researchers. We show that the number of parvalbumin+ interneurons in these 3 cortical areas-BA46, BA47, and BA9-is significantly reduced in autism compared with controls. The number of calbindin+ and calretinin+ interneurons did not differ in the cortical areas examined. Parvalbumin+ interneurons are fast-spiking cells that synchronize the activity of pyramidal cells through perisomatic and axo-axonic inhibition. The reduced number of parvalbumin+ interneurons could disrupt the balance of excitation/inhibition and alter gamma wave oscillations in the cerebral cortex of autistic subjects. These data will allow development of novel treatments specifically targeting parvalbumin interneurons.
DOI: 10.15154/1338195
title: Cognitive remediation for individuals with psychosis: Efficacy and mechanisms of treatment effects

description: The popularity of cognitive remediation (CR) interventions for individuals
with psychosis is in part based on the well-established link between cognition and
functioning and the assumption that by targeting cognition, function can improve. While
numerous trials have reported CR's efficacy, it is still not considered an evidencebased
treatment. Importantly, little is known about the mechanisms through which it
may affect functioning. Method: In this study, we evaluated CR's proximal and distal
effects, and examined potential mechanisms. Seventy-five individuals with psychotic
disorders were randomized to a combination of strategy-based and drill and practice
cognitive remediation (CR) or Wait-List Control (WLC), with assessments of training
task performance, neurocognition, functional capacity, symptoms and functioning
conducted at baseline, end of the 2-month intervention, and 2-month follow-up (FU).
Results: Compared to TAU, CR was associated with large post-training improvements
on training tasks targeting attention, visuospatial memory, and verbal learning and
memory, with persisting group differences at 2-month follow-up. These generalized to
mostly large improvements on neuropsychological measures targeting visuospatial
memory, verbal learning and memory, delayed verbal memory, and verbal working
memory. While there were no CR-associated improvements on measures of functional
capacity, symptoms, or a self-report measure of independent living skills, there was an
effect on an interviewer-rated measure of functioning (QLS), which appeared primarily
driven by the Intrapsychic Foundations subscale. Finally, for those randomized to CR,
there were significant, medium-sized correlations between training task improvement,
neuropsychological improvement and functioning measures. Conclusions: this
suggests a complex, multifactorial relationship between CR, cognitive and functional
change.
DOI: 10.15154/1338252
title: Identifying Person-Centered Clinical Net Benefit of Psychotropic Medication Treatment Using Latent Variable Techniques: Evidence from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

description: Subject level data for associated publication
DOI: 10.15154/1338620
title: The evolution and population diversity of human-specific segmental duplications

description: Subject level data for associated publication
DOI: 10.15154/1340302
title: Paternally inherited noncoding structural variants contribute to autism

description: Subject level data for associated publication
DOI: 10.15154/1340671
title: Targeted sequencing identifies 91 neurodevelopmental disorder risk genes with autism and developmental disability biases

description: Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most pathogenic genes are not known. We sequenced 208 candidate genes from &gt;11,730 patients and &gt;2,867 controls. We report 91 genes with an excess of de novo mutations or private disruptive mutations in 5.7% of patients, including 38 novel NDD genes. Drosophila functional assays of a subset bolster their involvement in NDDs. We identify 25 genes that show a bias for autism versus intellectual disability and highlight a network associated with high-functioning autism (FSIQ&gt;100). Clinical follow-up for NAA15, KMT5B, and ASH1L reveals novel syndromic and non-syndromic forms of disease. 

[Note: Upload of individual sample-level raw data files is ongoing and expected to be completed by 02/28/2017.]
DOI: 10.15154/1342749
title: One thousand somatic SNVs per skin fibroblast cell set baseline of mosaic mutational load with patterns that suggest proliferative origin

description: Few studies have been conducted to understand post-zygotic accumulation of mutations in cells of the healthy human body. We reprogrammed 32 skin fibroblast cells from families of donors into human induced pluripotent stem cell (hiPSC) lines. The clonal nature of hiPSC lines allows a high-resolution analysis of the genomes of the founder fibroblast cells without being confounded by the artifacts of single cell whole genome amplification. We estimate that on average a fibroblast cell in children has 1,035 mostly benign mosaic SNVs. On average, 235 SNVs could be directly confirmed in the original fibroblast population by ultra-deep sequencing, down to an allele frequency (AF) of 0.1%. More sensitive droplet digital PCR experiments confirmed more SNVs as mosaic with AF as low as 0.01%, suggesting that 1,035 mosaic SNVs per fibroblast cell is the true average. Similar analyses in adults revealed no significant increase in the number of SNVs per cell, suggesting that a major fraction of mosaic SNVs in fibroblasts arises during development. Mosaic SNVs were distributed uniformly across the genome and were enriched in a mutational signature previously observed in cancers and in de novo variants and which, we hypothesize, is a hallmark of normal cell proliferation. Finally, AF distribution of mosaic SNVs had distinct narrow peaks, which could be a characteristic of clonal cell selection, clonal expansion, or both. These findings reveal a large degree of somatic mosaicism in healthy human tissues, link de novo and cancer mutations to somatic mosaicism and couple somatic mosaicism with cell proliferation.
DOI: 10.15154/1343428
title: Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder.

description: The efficacy of a peer-mediated, theatre-based intervention on social competence in participants with autism spectrum disorder (ASD) was tested. Thirty 8-to-14 year-olds with ASD were randomly assigned to the treatment (n = 17) or a wait-list control (n = 13) group. Immediately after treatment, group effects were seen on social ability, (d = .77), communication symptoms (d = -.86), group play with toys in the company of peers (d = .77), immediate memory of faces as measured by neuropsychological (d = .75) and ERP methods (d = .93), delayed memory for faces (d = .98), and theory of mind (d = .99). At the 2 month follow-up period, group effects were detected on communication symptoms (d = .82). The results of this pilot clinical trial provide initial support for the efficacy of the theatre-based intervention.
DOI: 10.15154/1345184
title: Lack of early improvement with antipsychotics is a marker for subsequent non-response in behavioral and psychological symptoms of dementia: Analysis of CATIE-AD data

description: Objective: Prediction of response/non-response to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. We aimed to examine whether presence/absence of early improvement of BPSD with antipsychotics is associated with subsequent response/non-response.
Design: Post-hoc analysis of the Clinical Antipsychotic Trials in Intervention Effectiveness with Alzheimer’s Disease (CATIE-AD) study (2001-2004) (trial registration: NCT00015548). 
Setting: 45 sites in the United States.
Participants: 245 subjects (olanzapine, n=90; quetiapine, n=81; risperidone, n=74) with a DSM-IV diagnosis of dementia of the Alzheimer’s type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (Phase 1 of CATIE-AD).
Intervention: Subjects were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. 
Measurements: We examined associations between response at week 8, and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence/absence) of improvement/no improvement at week 2 for response at week 8 was examined.
Results: BPRS total score reduction at week 2 (mean percentage score reduction, 12.6%) was significantly associated with response at week 8 (odds ratio, 1.18; 95% CI, 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71) with sensitivity, specificity, PPV, and NPV of 0.76, 0.65, 0.69, and 0.72, respectively.
Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent non-response in BPSD.
DOI: 10.15154/1345819
title: How anxious do you think I am? Relationship between state and trait anxiety in children with and without ASD during social tasks

description: Individuals with autism spectrum disorder
(ASD) often exhibit increased anxiety, even in non-stressful
situations. We investigate general anxiousness (anxiety
trait) and responses to stressful situations (anxiety state) in
22 adolescents with ASD and 32 typically developing controls.
We measured trait anxiety with standardized self- and
parent-reported questionnaires. We used a Biopac system to
capture state anxiety via skin conductance responses, mean
heart rate and heart rate variability during high- and lowanxiety
tasks. Results reveal higher trait anxiety in adolescents
with ASD (p &lt; 0.05) and no group difference in state
anxiety. Increased parent-reported trait anxiety may predict
decreased state anxiety during high-stress conditions.
Together, these findings suggest that higher trait anxiety
may result in dampened physical responses to stress.
DOI: 10.15154/1346187
title: Training Parents of Youth with Autism Spectrum Disorder to Advocate for Adult Disability Services: Results from a Pilot Randomized Controlled Trial.

description: This study presents findings from a pilot randomized controlled trial, testing a 12-week intervention to train parents of youth with autism spectrum disorder (ASD) to advocate for adult disability services-the Volunteer Advocacy Program-Transition (VAP-T). Participants included 41 parents of youth with ASD within 2 years of high school exit, randomly assigned to a treatment (N = 20) or wait-list control (N = 21) group. Outcomes, collected before and after the intervention, included parental knowledge about adult services, advocacy skills-comfort, and empowerment. The VAP-T had acceptable feasibility, treatment fidelity, and acceptability. After participating in the VAP-T, intervention parents (compared to controls) knew more about the adult service system, were more skilled/comfortable advocating, and felt more empowered.
DOI: 10.15154/1351615
title: Upper limb motor coordination based early diagnosis in high risk subjects for Autism

description: Autism is a lifelong condition present from early childhood. Medical specialists' diagnosis autism based on observation is of great difficulty in communicating, difficulties for forming relationships with other people, and delayed speech. The scientists tried to discover other early signs to reach the early detection of Autism Spectrum Disorders (ASD). Early diagnosing is very important to initiate and improve treatment results. One of these signs is based on examination of upper limb motor movements. This study aims to determine whether a simple upper limb motor movement could be useful to classify High Risk (HR) infants for autism and comparison infants with Low Risk (LR) for autism. Also, this paper presents a computational intelligence method that uses HR and LR subjects between the ages of 12 and 36 months to make an early autism diagnosing. The paper examined one task which asks to insert an object into a box. It analyzed the data by using Support Vector Machine (SVM) and Extreme Learning Machine (ELM). The results show engorging results in comparison to other state or art methods.