Digital health has emerged in recent years as a tool to optimize care delivery and promote treatment adherence among individuals with first-episode psychosis (FEP). Recent mandates for social distancing and sheltering in place due to the COVID-19 pandemic have catapulted efforts to provide ongoing coordinated specialty care (CSC) on virtual platforms. While prior evidence provides support for the general implementation of virtual individual therapy, there is limited guidance and evidence for the adoption of group teletherapy. Here we describe our efforts to implement group teletherapy for two small cohorts of individuals with FEP receiving care in a coordinated specialty care clinic using methods adopted from Acceptance and Commitment Therapy. We observed high adherence with group visits as well as client satisfaction across groups. Based on our results, we have taken efforts to implement virtual group therapy more permanently in our clinic. Our experience provides guidance and a model for integration of virtual group therapy within CSC. PRACTITIONER POINTS In-person group therapy can be adapted as an online treatment modality for individuals with first-episode psychosis (FEP). Group teletherapy is both accessible and satisfactory to individuals with FEP. Group teletherapy has potential as a more standard and widespread treatment modality within coordinated specialty care for FEP.Pathogenic variants in the BRCA1 and BRCA2 genes are well known causes of hereditary breast and ovarian cancer. Other genes involved in the homologous recombination pathway can also be associated with increased probability of cancer development, for example, breast and ovarian cancer, prostate and pancreatic cancer, colorectal cancer, and even childhood tumors like medulloblastoma. Traditionally, patients and families likely to harbor a genetic predisposition have been identified using personal and family history. Several checklists and risk prediction tools have proven to be useful in the clinic. Phenformin Through the widespread application of next generation sequencing of tumor tissue, a growing number of individuals with genetic cancer predisposition is now identified molecularly, even in the absence of a suggestive family history. Any constitutional variant identified during molecular genetic testing has to be assessed for its relevance, both functionally and in the context of patient phenotype. Variant curation is time consuming, but has been increasingly standardized by introduction of several guidelines to allow reliable and reproducible classification of constitutional variants. Variant classification by expert panels using data mining tools, evidence-based decision trees and gene specific criteria represents the gold standard. Participation of geneticists in molecular tumor boards facilitates the curation of potential constitutional variants, germline validation and thus directing the patient to appropriate counselling and care pathways. Due to the high relevance of germline variants for treatment and surveillance of the index patient and predictive testing and surveillance of relatives, only pathogenic or likely pathogenic variants must be used for clinical decision-making.Tall fescue (Festuca arundinacea) is an important grass species worldwide, but temperature stress severely affects its distribution and yield. Transcription factors (TFs), as the master switches in sophisticated regulatory networks, play essential roles in plant growth development and abiotic stress responses. In this study, the comparative transcriptome analysis was performed to explore the commonalities and differences in the response of TFs to the heat (40 °C), cold (10 °C) and control (22 °C) conditions. A total of 877 TF genes belonging to 35 families were identified. Most of them (784) were differentially expressed genes (DEG), indicating TF genes actively responded to temperature stress. The expression of bZIP and GTF family members was up-regulated when exposed to both heat and cold, but conversely, the expression of the most WRKY and NAC families members decreased. The HSF and GTE families and DREB2B were up-regulated upon heat, while bHLH, MYB, HD-ZIP and ERF families were elevated under cold stress. The TFs involved in ‘Plant hormone signal transduction’, ‘Plant-pathogen interaction’, ‘Circadian rhythm’ play major roles in responding to temperature stresses. The results showed the temperature threats up-regulated the expression of stress tolerance-related genes, and down-regulated those genes associated with growth and disease resistance, indicating TFs exert crucial roles in plant adaptation to an adverse environment. This study profiled the responsive pattern of TFs to temperature stresses, partially explained the mechanism of adaptations of cold-season forage crops and screened many candidate stress-tolerant TF genes.

To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic oligodontia, and the functional impact of these variants.

Whole exome sequencing and Sanger sequencing were utilized to detect gene variants in a cohort of 80 patients diagnosed with non-syndromic oligodontia. Bioinformatic and conformational analyses, fluorescence microscopy and luciferase reporter assay were employed to explore the functional impact.

We identified three novel variants in the PAX9, including two frameshift variants (c.211_212insA; p.I71Nfs*246 and c.236_237insAC; p.T80Lfs*6), and one missense variant (c.229C>G; p.R77G). Familial co-segregation verified an autosomal-dominant inheritance pattern. Conformational analyses revealed that the variants resided in the paired domain, and could cause corresponding structural impairment of the PAX9 protein. Fluorescence microscopy showed abnormal subcellular localizations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants.

Our findings broaden the spectrum of PAX9 variants in patients with non-syndromic oligodontia and support that paired domain structural impairment and the dominant-negative effect are likely the underlying mechanisms of PAX9-related non-syndromic oligodontia. Our findings will facilitate genetic diagnosis and counselling, and help lay the foundation for precise oral health therapies.

Our findings broaden the spectrum of PAX9 variants in patients with non-syndromic oligodontia and support that paired domain structural impairment and the dominant-negative effect are likely the underlying mechanisms of PAX9-related non-syndromic oligodontia. Our findings will facilitate genetic diagnosis and counselling, and help lay the foundation for precise oral health therapies.