A next generation sequencing-based protocol for screening of variants of concern in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients\u27 clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD

Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3-20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted

Comprehensive Analysis of N6-Methyladenosine Regulatory Genes from <i>Citrus grandis</i> and Expression Profilings in the Fruits of “Huajuhong” (<i>C. grandis</i> “Tomentosa”) during Various Development Stages

Citrus grandis “Tomentosa” (“Huajuhong”) is a famous traditional Chinese medicine. The aim of the present study is to provide a comprehensive characterization of the m6A regulatory genes from C. grandis, and examine their expression patterns in fruits of C. grandis “Tomentosa” during various developmental stages. A total of 26 N6-methyladenosine (m6A) regulatory proteins were identified from the genome of C. grandis, which were distributed across nine chromosomes in C. grandis. Phylogenetic relationships revealed that all m6A regulatory genes were divided into groups of m6A writers, erasers, and readers. The m6A writer groups included CgMTA, CgMTB, and CgMTC three MTs (methyltransferases), one CgVIR (virilizer), one CgHAKAI (E3 ubiquitin ligase HAKAI), and one CgFIP37 (FKBP interacting protein 37). Moreover, 10 CgALKBH (α-ketoglutarate-dependent dioxygenase homolog) members (numbered from CgALKBH1 to CgALKBH10) and 10 CgECT (C-terminal region) members (numbered from CgECT1 to CgECT10) in C. grandis were identified as m6A erasers and readers, respectively. The domain structures and motif architectures among the groups of m6A writers, erasers, and readers were diverse. Cis-acting elements in the promoters of the 26 m6A regulatory genes predicted that the abscisic acid-responsive (ABA) element (ABRE) was present on the promoters of 19 genes. In addition, the expression profiles of all m6A regulatory genes were examined in the fruits of two varieties of C. grandis “Tomentosa” during different growth stages to give basic hints for further investigation of the function of the N6-methyladenosine regulatory genes in C. grandis “Tomentosa”

Comprehensive Analysis of N6-Methyladenosine Regulatory Genes from Citrus grandis and Expression Profilings in the Fruits of &ldquo;Huajuhong&rdquo; (C. grandis &ldquo;Tomentosa&rdquo;) during Various Development Stages

Citrus grandis &ldquo;Tomentosa&rdquo; (&ldquo;Huajuhong&rdquo;) is a famous traditional Chinese medicine. The aim of the present study is to provide a comprehensive characterization of the m6A regulatory genes from C. grandis, and examine their expression patterns in fruits of C. grandis &ldquo;Tomentosa&rdquo; during various developmental stages. A total of 26 N6-methyladenosine (m6A) regulatory proteins were identified from the genome of C. grandis, which were distributed across nine chromosomes in C. grandis. Phylogenetic relationships revealed that all m6A regulatory genes were divided into groups of m6A writers, erasers, and readers. The m6A writer groups included CgMTA, CgMTB, and CgMTC three MTs (methyltransferases), one CgVIR (virilizer), one CgHAKAI (E3 ubiquitin ligase HAKAI), and one CgFIP37 (FKBP interacting protein 37). Moreover, 10 CgALKBH (&alpha;-ketoglutarate-dependent dioxygenase homolog) members (numbered from CgALKBH1 to CgALKBH10) and 10 CgECT (C-terminal region) members (numbered from CgECT1 to CgECT10) in C. grandis were identified as m6A erasers and readers, respectively. The domain structures and motif architectures among the groups of m6A writers, erasers, and readers were diverse. Cis-acting elements in the promoters of the 26 m6A regulatory genes predicted that the abscisic acid-responsive (ABA) element (ABRE) was present on the promoters of 19 genes. In addition, the expression profiles of all m6A regulatory genes were examined in the fruits of two varieties of C. grandis &ldquo;Tomentosa&rdquo; during different growth stages to give basic hints for further investigation of the function of the N6-methyladenosine regulatory genes in C. grandis &ldquo;Tomentosa&rdquo;

Comprehensive Analysis of Jumonji Domain C Family from <i>Citrus grandis</i> and Expression Profilings in the Exocarps of “Huajuhong” (<i>Citrus grandis</i> “Tomentosa”) during Various Development Stages

Citrus grandis “Tomentosa” (“Huajuhong”) is a famous Traditional Chinese Medicine. In this study, a total of 18 jumonji C (JMJC) domain-containing proteins were identified from C. grandis. The 18 CgJMJCs were unevenly located on six chromosomes of C. grandis. Phylogenetic analysis revealed that they could be classified into five groups, namely KDM3, KDM4, KDM5, JMJC, and JMJD6. The domain structures and motif architectures in the five groups were diversified. Cis-acting elements on the promoters of 18 CgJMJC genes were also investigated, and the abscisic acid-responsive element (ABRE) was distributed on 15 CgJMJC genes. Furthermore, the expression profiles of 18 CgJMJCs members in the exocarps of three varieties of “Huajuhong”, for different developmental stages, were examined. The results were validated by quantitative real-time PCR (qRT-PCR). The present study provides a comprehensive characterization of JMJC domain-containing proteins in C. grandis and their expression patterns in the exocarps of C. grandis “Tomentosa” for three varieties with various development stages

Comprehensive Analysis of Jumonji Domain C Family from Citrus grandis and Expression Profilings in the Exocarps of &ldquo;Huajuhong&rdquo; (Citrus grandis &ldquo;Tomentosa&rdquo;) during Various Development Stages

Citrus grandis &ldquo;Tomentosa&rdquo; (&ldquo;Huajuhong&rdquo;) is a famous Traditional Chinese Medicine. In this study, a total of 18 jumonji C (JMJC) domain-containing proteins were identified from C. grandis. The 18 CgJMJCs were unevenly located on six chromosomes of C. grandis. Phylogenetic analysis revealed that they could be classified into five groups, namely KDM3, KDM4, KDM5, JMJC, and JMJD6. The domain structures and motif architectures in the five groups were diversified. Cis-acting elements on the promoters of 18 CgJMJC genes were also investigated, and the abscisic acid-responsive element (ABRE) was distributed on 15 CgJMJC genes. Furthermore, the expression profiles of 18 CgJMJCs members in the exocarps of three varieties of &ldquo;Huajuhong&rdquo;, for different developmental stages, were examined. The results were validated by quantitative real-time PCR (qRT-PCR). The present study provides a comprehensive characterization of JMJC domain-containing proteins in C. grandis and their expression patterns in the exocarps of C. grandis &ldquo;Tomentosa&rdquo; for three varieties with various development stages

Electrospun polycaprolactone (PCL)-amnion nanofibrous membrane prevents adhesions and promotes nerve repair in a rat model of sciatic nerve compression.

Adhesion and scarring after neural surgery are detrimental to nerve regeneration and functional recovery. Amniotic membranes have been used in tissue repair due to their immunogenicity and richness in cytokines. In this study, an electrospun polycaprolactone (PCL)-amnion nanofibrous membrane was prepared for the treatment of sciatic nerve compression in a rat model. The effects of the PCL-amnion nanofibrous membrane on the prevention of adhesion formation and nerve regeneration were evaluated using electrophysiology and histological analyses. Compared with the medical chitosan hydrogel dressing, the PCL-amnion nanofibrous membrane significantly reduced peripheral nerve adhesion and promoted the rapid recovery of nerve conduction. Moreover, the immunohistochemical analysis identified more Schwann cells and less pro-inflammatory M1 macrophages in the PCL-amnion group. Western blot and RT-PCR results showed that the expression levels of type-Ⅰ and Ⅲ collagen in the PCL-treated rats were half of those in the control group after 12 weeks, while the expression level of nerve growth factor was approximately 3.5 times that found in the rats treated with medical chitosan hydrogel. In summary, electrospun PCL-amnion nanofibrous membranes can effectively reduce adhesion after neural surgery and promote nerve repair and regeneration. The long-term retention in vivo and sustained release of cytokines make PCL-amnion a promising biomaterial for clinical application

Multiobjective Environmentally Sustainable Optimal Design of Dedicated Connected Autonomous Vehicle Lanes

The emergence of connected autonomous vehicles (CAVs) is not only improving the efficiency of transportation, but also providing new opportunities for the sustainable development of transportation. Taking advantage of the energy consumption of CAVs to promote the sustainable development of transportation has attracted extensive public attention in recent years. This paper develops a mathematical approach to investigating the problem of the optimal implementation of dedicated CAV lanes while simultaneously considering economic and environmental sustainability. Specifically, the problem is described as a multi-objective bi-level programming model, in which the upper level is to minimize the system-level costs including travel time costs, CAV lane construction cost, and emission cost, whereas the lower level characterizes the multi-class network equilibrium with a heterogeneous traffic stream consisting of both human-driven vehicle (HVs) and CAVs. To address the multi-objective dedicated CAV lane implement problem, we propose an integrated solution framework that integrates a non-dominated sorting genetic algorithm II (NSGA-II) algorithm, diagonalized algorithm, and Frank–Wolfe algorithm. The NSGA-II was adopted to solve the upper-level model, i.e., hunting for the optimal CAV lanes implementation schemes. The diagonalized Frank–Wolfe (DFW) algorithm is used to cope with multi-class network equilibrium. Finally, numerical experiments were conducted to demonstrate the effectiveness of the proposed model and solution method. The experimental results show that the total travel time cost, total emission cost, and total energy consumption were decreased by about 12.03%, 10.42%, and 9.4%, respectively, in the Nguyen–Dupuis network as a result of implementing the dedicated CAV lanes

Qual Research: Municipal officials\u27 perspectives on policymaking for addressing obesity and health equity

The aim of this qualitative research was to understand decision-making for policies impacting obesity and community health, and perspectives on obesity and related health disparities among local policymakers from municipalities experiencing obesity disparities. The dataset includes transcripts from 20 semi-structured interviews with local elected and top-appointed officials from municipalities across the United States, conducted between December 2020 and April 2021. The Institutional Review Board of Washington University in St. Louis approved this study (#202001197)

Correction: Huang et al. A Next Generation Sequencing-Based Protocol for Screening of Variants of Concern in Autism Spectrum Disorder. Cells 2022, 11, 10

In the original publication [...