Beyond the Spectrum: Subtype-Specific Molecular Insights into Autism Spectrum Disorder Via Multimodal Data Integration.

Some toddlers with autism spectrum disorder (ASD) have mild social symptoms and developmental improvement in skills, but for others, symptoms and abilities are moderately or even severely affected. Those with profound autism have the most severe social, language, and cognitive symptoms and are at the greatest risk of having a poor developmental outcome. The little that is known about the underlying biology of this important profound autism subtype, points clearly to embryonic dysregulation of proliferation, differentiation and neurogenesis.

Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms.

Background: Social affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known.

Methods: Because ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject).

Level of Attention to Motherese Speech as an Early Marker of Autism Spectrum Disorder.

Importance: Caregivers have long captured the attention of their infants by speaking in motherese, a playful speech style characterized by heightened affect. Reduced attention to motherese in toddlers with autism spectrum disorder (ASD) may be a contributor to downstream language and social challenges and could be diagnostically revealing.

Objective: To investigate whether attention toward motherese speech can be used as a diagnostic classifier of ASD and is associated with language and social ability.

Examination of the impact of the program on equitable access to care within the screen-evaluate-treat chain in toddlers with autism spectrum disorder.

Delays in autism spectrum disorder identification and access to care could impact developmental outcomes. Although trends are encouraging, children from historically underrepresented minority backgrounds are often identified at later ages and have reduced engagement in services. It is unclear if disparities exist all along the screen-evaluation-treatment chain, or if early detection programs such as that standardize, these steps are effective at ameliorating disparities.

A predictive ensemble classifier for the gene expression diagnosis of ASD at ages 1 to 4 years.

Autism Spectrum Disorder (ASD) diagnosis remains behavior-based and the median age of diagnosis is ~52 months, nearly 5 years after its first-trimester origin. Accurate and clinically-translatable early-age diagnostics do not exist due to ASD genetic and clinical heterogeneity. Here we collected clinical, diagnostic, and leukocyte RNA data from 240 ASD and typically developing (TD) toddlers (175 toddlers for training and 65 for test).

Atypical genomic cortical patterning in autism with poor early language outcome.

Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here, we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT), present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by a secondary and independent genomic patterning effect on CT.

Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.

Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.

Get SET Early to Identify and Treatment Refer Autism Spectrum Disorder at 1 Year and Discover Factors That Influence Early Diagnosis.

Objectives: To examine the impact of a new approach, Get SET Early, on the rates of early autism spectrum disorder (ASD) detection and factors that influence the screen-evaluate-treat chain.

Study Design: After attending Get SET Early training, 203 pediatricians administered 57 603 total screens using the Communication and Symbolic Behavior Scales Infant-Toddler Checklist at 12-, 18-, and 24-month well-baby examinations, and parents designated presence or absence of concern. For screen-positive toddlers, pediatricians specified if the child was being referred for evaluation, and if not, why not.

Multiple freeze-thaw cycles lead to a loss of consistency in poly(A)-enriched RNA sequencing.

Background: Both RNA-Seq and sample freeze-thaw are ubiquitous. However, knowledge about the impact of freeze-thaw on downstream analyses is limited. The lack of common quality metrics that are sufficiently sensitive to freeze-thaw and RNA degradation, e.

A perturbed gene network containing PI3K-AKT, RAS-ERK and WNT-β-catenin pathways in leukocytes is linked to ASD genetics and symptom severity.

Hundreds of genes are implicated in autism spectrum disorder (ASD), but the mechanisms through which they contribute to ASD pathophysiology remain elusive. Here we analyzed leukocyte transcriptomics from 1- to 4-year-old male toddlers with ASD or typical development from the general population. We discovered a perturbed gene network that includes highly expressed genes during fetal brain development.

Evaluation of the Diagnostic Stability of the Early Autism Spectrum Disorder Phenotype in the General Population Starting at 12 Months.

Importance: Universal early screening for autism spectrum disorder (ASD) in primary care is becoming increasingly common and is believed to be a pivotal step toward early treatment. However, the diagnostic stability of ASD in large cohorts from the general population, particularly in those younger than 18 months, is unknown. Changes in the phenotypic expression of ASD across early development compared with toddlers with other delays are also unknown.

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome.

Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers.

Genetic mechanisms underlying abnormal early neural development in toddlers with Autism Spectrum Disorder (ASD) remain uncertain due to the impossibility of direct brain gene expression measurement during critical periods of early development. Recent findings from a multi-tissue study demonstrated high expression of many of the same gene networks between blood and brain tissues, in particular with cell cycle functions. We explored relationships between blood gene expression and total brain volume (TBV) in 142 ASD and control male toddlers.

Targeted Metabolomic Analysis of Head and Neck Cancer Cells Using High Performance Ion Chromatography Coupled with a Q Exactive HF Mass Spectrometer.

In this study, we have demonstrated a targeted metabolomics method for analysis of cancer cells, based on high-performance ion chromatography (IC) separation, Q Exactive HF MS for high-resolution and accurate-mass (HR/AM) measurement and the use of stable isotope-labeled internal standards for absolute quantitation. Our method offers great technical advantages for metabolite analysis, including exquisite sensitivity, high speed and reproducibility, and wide dynamic range. The high-performance IC provided fast separation of cellular metabolites within 20 min and excellent resolving power for polar molecules including many isobaric metabolites.

Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices.

Importance: The identification of genomic signatures that aid early identification of individuals at risk for autism spectrum disorder (ASD) in the toddler period remains a major challenge because of the genetic and phenotypic heterogeneity of the disorder. Generally, ASD is not diagnosed before the fourth to fifth birthday.

Objective: To apply a functional genomic approach to identify a biologically relevant signature with promising performance in the diagnostic classification of infants and toddlers with ASD.

Metabolomic profiling of anionic metabolites in head and neck cancer cells by capillary ion chromatography with Orbitrap mass spectrometry.

A highly sensitive platform coupling capillary ion chromatography (Cap IC) with Q Exactive mass spectrometer has been developed for metabolic profiling of head and neck squamous cell carcinoma (HNSCC) cells. The Cap IC allowed an excellent separation of anionic polar metabolites, and the sensitivities increased by up to 100-fold compared to reversed-phase liquid chromatography and hydrophilic interaction chromatography performed at either high- or capillary-flow rates. The detection limits for a panel of standard metabolites were between 0.

Blood-based gene expression signatures of infants and toddlers with autism.

Objective: Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with autism have yet emerged.

Method: Using a community-based, prospective, longitudinal method, we identified 60 infants and toddlers at risk for ASDs (autistic disorder and pervasive developmental disorder), 34 at-risk for language delay, 17 at-risk for global developmental delay, and 68 typically developing comparison children.

A case control study of the implementation of change model versus passive dissemination of practice guidelines for compliance in monitoring for metabolic syndrome.

We developed an intervention to improve compliance with guidelines for monitoring metabolic syndrome and compared compliance prior to intervention and three times post-intervention at three community mental health clinics in Texas. One test clinic received intervention and two other clinics served as controls. Fifty random charts were reviewed from each clinic for three specific, 1-2 weeks periods over the course of 18 months.

Interrater reliability of using brief standardized outcome measures in a community mental health setting.

Objective: Given psychiatry's need to implement measurement-based care, the study examined whether direct-care staff could reliably administer brief positive and negative symptom instruments to track symptom changes and inform clinical decision making.

Methods: Raters (82 case managers) were assessed at baseline. Training was provided for individuals not meeting reliability criteria.

Community mental health agency views of research.

We examined community mental health center staff perceptions of ongoing research within their agency. We interviewed upper management and conducted focus groups with medical staff, non-medical clinicians, and administrative staff. Participants were asked about (1) their attitudes towards research in general, agency research and towards the principal academic institution doing research with clients, (2) their perceptions of the value of research and (3) ideas for improving the collaboration.

Barriers to, and strategies for, starting a long acting injection clinic in a community mental health center.

As many as 50% of patients with schizophrenia do not take oral antipsychotic medications as prescribed, yet long acting injections are rarely utilized. Community agencies that serve this population are often over-burdened and poorly funded. There are negative attitudes on the part of both physicians and consumers about injections.

Engineering of N. benthamiana L. plants for production of N-acetylgalactosamine-glycosylated proteins--towards development of a plant-based platform for production of protein therapeutics with mucin type O-glycosylation.

Background: Mucin type O-glycosylation is one of the most common types of post-translational modifications that impacts stability and biological functions of many mammalian proteins. A large family of UDP-GalNAc polypeptide:N-acetyl-α-galactosaminyltransferases (GalNAc-Ts) catalyzes the first step of mucin type O-glycosylation by transferring GalNAc to serine and/or threonine residues of acceptor polypeptides. Plants do not have the enzyme machinery to perform this process, thus restricting their use as bioreactors for production of recombinant therapeutic proteins.

Public-academic partnerships: tools for mental health agencies to evaluate research protocols.

Research involving community mental health center clients, resources, or both can affect clinical care, administrative processes, and costs. To help agencies identify and quantify these effects, a stakeholder group examined and discussed a range of protocols and then developed questionnaires and rating scales for agency use. The purpose of these materials is to make explicit the risks, costs, and benefits of a research protocol so an agency can make informed decisions about protocol approval and implementation.

Suppression of lipopolysaccharide-induced inflammatory responses in RAW 264.7 murine macrophages by aqueous extract of Clinopodium vulgare L. (Lamiaceae).

Ethnopharmacological Relevance: The wild basil Clinopodium vulgare L. is commonly used in Bulgarian folk medicine for treatment of irritated skin, mastitis- and prostatitis-related swelling, as well as for some disorders accompanied with significant degree of inflammation (e.g.

Public-academic partnerships: research in community mental health settings: a practicum experience for researchers.

Applying research findings to community mental health practices is slowed by provider concerns that research participants often differ from community populations in duration of illness, comorbid conditions, and illness severity. Selecting participants from community settings makes research results demonstrably relevant, but researchers and community providers can be mistrustful of one another, feeling that the other has little understanding of their needs and work. This mistrust impedes patient referrals for research.