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Understanding the role of therapeutic process factors in treatment change may prove useful for discerning why some autistic youth benefit from psychosocial interventions that target emotional and psychological aspects of mental health, while others do not. The aim of the current study was to synthesize what is currently known about therapeutic process factors in mental health treatment of emotional and psychological challenges for autistic youth, regarding how process factors have been measured in past research, and the relation between process factors and treatment outcome. A systematic review of the literature was conducted to narratively synthesize all articles published up until June 2021. Methodological quality of included studies was appraised. Twenty-five studies met inclusion criteria. Process factors assessed across studies included relational factors; treatment expectations, readiness, and satisfaction; and treatment engagement from youth and their parents. Process-outcome associations were reported for a limited number of constructs. There is a limited, albeit growing, body of high-quality research evaluating the role of process factors in the treatment of mental health issues for autistic youth. Future research should continue to examine process factors in relation to treatment outcome, and validate measures to accurately capture process-related constructs in mental health treatment for this population. Greater understanding of therapy processes can lead to developing evidence-informed strategies that clinicians can implement to promote positive expectations, relationships, and engagement.

This pilot study examined associations between transdiagnostic symptoms and parent-perceived parent-child relationship quality in treatment-seeking families of children with neurodevelopmental disabilities, and interactions among clinical symptoms and cognitive functioning. Sixty-three children between 8 to 13 years of age and their caregivers were assessed at baseline while seeking cognitive behaviour therapy for emotion regulation and mental health difficulties. Diagnoses included autism, ADHD, cerebral palsy, and learning disability, with 52% of children having multiple diagnoses. Parent-perceived parent-child relationship quality was assessed by the Positive Affect Index, autism symptoms (e.g., social communication, repetitive behaviours) by the Social Responsiveness Scale, Second Edition, mental health (i.e., internalizing problems, externalizing problems, behavioural symptoms) by the Behaviour Assessment Scale for Children, Third Edition, and IQ by the Weschler Abbreviated Scale of Intelligence, Second Edition. Results revealed that higher IQ scores and greater social communication challenges, externalizing problems, and behavioural symptoms, were associated with lower parent-child relationship quality. Interaction effects were found between IQ and social communication challenges, reflecting significantly stronger relationships between social communication challenges and lower parent-child relationship quality in the context of higher IQ. Understanding the interactions between cognitive functioning and social communication challenges can help to inform individualized supports, and advocate for a transdiagnostic approach to intervention.

Supplementary Figure 7 - PDF file 111K, Characterization of myeloid cells in lung, tumor, spleen, and lymph nodes

Supplementary Figure 1 - PDF file 183K, Overproduction of immature myeloid cells in both tumor bearing mice and cancer patients, flow cytometry analysis and sorting

Supplementary Figure 4 - PDF file 129K, Validation of over expression of TGFbeta1, IL-4, IL10, as well as Arginase1 and iNOS in Tgfbr2

Supplementary Figure 3 - PDF file 76K, IFN-gamma production by T cells and its effect on tumor growth in Tgfbr2MyeKOand Tgfbr2flox/flox control mice

Supplementary Figure 8 - PDF file 84K, Immune cell profiling and IFN-gamma production in CD8 T cells in tumor tissues between Tgfbr2flox/flox and Tgfbr2MyeKO mice bearing 4T1 tumors

Supplementary Figure 9 - PDF file 150K, Gating strategy, sorting efficiency, and TbetaRII expression in myeloid cell subsets

TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2MyeKO bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-β1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2MyeKO mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-β receptor II expression. Our studies show that myeloid-specific TGF-β signaling is an essential component of the metastasis-promoting puzzle of TGF-β. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.Significance: Our study identifies myeloid-specific TGF-β signaling as a critical mediator in tumor metastasis, distinct from the tumor-suppressive effect of TGF-β signaling in epithelial cells, fibroblasts, and T cells. We further provide mechanistic insight into host antitumor immunity and suggest a cell type–specific cancer-targeting strategy. Cancer Discov; 3(8); 936–51. ©2013 AACR.See related commentary by Souza-Fonseca-Guimaraes and Smyth, p. 846This article is highlighted in the In This Issue feature, p. 826

Supplementary Figure 5 - PDF file 382K, Analysis of percentage or number in B cells, T cells, or myeloid cell subsets in the lungs between Tgfbr2MyeKO and control littermates under normal or tumor conditions

Supplementary Figure Legends, Supplementary Tables 1-2 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 2 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Table 1. Th1 vs. Th2 Cytokine Trend. Supplementary Table 2. Effect of L-NAME on Radiation-induced Cytokine Expression.

Supplementary Figure 3 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 4 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 1 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 1 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 4 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 5 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 3 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 6 from Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors

Supplementary Figure 5 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Supplementary Figure 2 from mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of an Agonist CD40 Antibody in Cancer Treatment

Cognitive behavior therapy (CBT) is an effective treatment for many autistic children experiencing mental health problems, and parents are particularly involved in their psychotherapy. This study presents a conceptual framework of successful parent involvement in CBT for autistic children. Seventeen therapists (94% female) and 11 mothers were interviewed about their involvement in a CBT program for autistic children ages 8-13 years. The conceptual framework depicts how parent involvement varies depending on child, parent, and environmental factors. Parents’ contributions to therapy were grouped into five main roles. Parents’ beliefs and attitudes toward therapy also influenced their involvement. This is the first study to empirically investigate how parents of autistic children contribute to the therapeutic process in CBT.

Autistic youth have an increased risk of mental health problems. Despite the efficacy of various psychotherapeutic approaches for autistic youth, they often do not receive these interventions. Research is needed to identify patterns of effective treatment for autistic youth and whether they differ from those used for youth with other neurodevelopmental conditions (e.g., attention-deficit hyperactivity disorder; ADHD). We compared clinicians' (N = 557) knowledge, confidence and practices when treating autistic youth and youth with ADHD. Although ratings were moderately high overall and similar interventions were used for both groups, clinicians were significantly less knowledgeable and confident when supporting autistic clients compared to clients with ADHD. Thus, improving clinician perspectives may help facilitate treatment for autistic youth with mental health problems.

Autistic children and adolescents are more likely than non-autistic youth to experience mental health problems, such as anxiety or depression, but less likely to receive psychotherapy to address these concerns. Recent research indicates that clinician factors, such as knowledge, attitudes, confidence and beliefs, can impact their decisions to provide care, though this work has primarily focused on adults or within the context of one kind of treatment (cognitive behaviour therapy). The current study examined psychological predictors (e.g. attitudes and confidence) of clinicians’ intention to deliver psychotherapy to autistic youth and those with attention-deficit hyperactivity disorder. Participants included 611 clinicians across publicly funded agencies in Ontario, Canada. Multiple mediation analyses revealed that clinician knowledge on mental health-related topics (e.g. core symptoms, developing treatment plans and identifying progress towards treatment goals) was associated with intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, and normative pressures and attitudes partially mediated this association. Clinicians felt less likely to treat autistic clients than clients with attention-deficit hyperactivity disorder, partly because of differences in attitudes, normative pressures and knowledge. This research suggests that targeted training around autism and mental health care may be a useful initiative for agency staff. Lay abstract Autistic children and youth often experience mental health problems, such as anxiety, depression and behavioural challenges. Although there are therapy programmes that have been found helpful in reducing these issues, such as cognitive behaviour therapy, autistic children often struggle to receive adequate mental health care. Clinicians’ knowledge, attitudes, confidence and beliefs about treating mental health problems in autistic people may be related to their choices in providing psychotherapy. Across Ontario, Canada, 611 mental health clinicians, working in publicly funded agencies, completed an online survey about their experiences and opinions on delivering therapy for autistic clients compared to those with attention-deficit hyperactivity disorder. Clinician knowledge was associated with their intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, partly because of their attitudes and the social pressures or values they felt. Clinicians reported feeling less intent on providing therapy to autistic youth compared to youth with attention-deficit hyperactivity disorder because of differences in their attitudes, social pressures and knowledge. This research can inform the training and educational initiatives for mental health practitioners.

The construction of human organs on demand remains a tantalizing vision to solve the organ donor shortage. Yet, engineering tissues that recapitulate the cellular and architectural complexity of native organs is a grand challenge. The use of organ building blocks (OBBs) composed of multicellular spheroids, organoids, and assembloids offers an important pathway for creating organ-specific tissues with the desired cellular-to-tissue-level organization. Here, we review the differentiation, maturation, and 3D assembly of OBBs into functional human tissues and, ultimately, organs for therapeutic repair and replacement. We also highlight future challenges and areas of opportunity for this nascent field.

Irg1 is an enzyme that generates itaconate, a metabolite that plays a key role in the regulation of inflammatory responses. Previous studies have implicated Irg1 as an important mediator in preventing excessive inflammation and tissue damage inMycobacterium tuberculosis(Mtb) infection. Here, we investigated the pattern recognition receptors and signaling pathways by whichMtbtriggers Irg1 gene expression by comparing the responses of control and genetically deficient BMDMs. Using this approach, we demonstrated partial roles for TLR-2 (but not TLR-4 or -9), MyD88 and NFκB signaling in Irg1 induction byMtbbacilli. In addition, drug inhibition studies revealed major requirements for phagocytosis and endosomal acidification in Irg1 expression triggered byMtbbut not LPS or PAM3CSK4. Importantly, theMtb-induced Irg1 response was highly dependent on the presence of the bacterial ESX-1 secretion system, as well as host STING and Type I IFN receptor (IFNAR) signaling with Type II IFN (IFN-γ) signaling playing only a minimal role. Based on these findings we hypothesize thatMtbinduces Irg1 expression in macrophagesviathe combination of two independent triggers both dependent on bacterial phagocytosis: 1) a major signal stimulated by phagocytizedMtbproducts released by an ESX-1-dependent mechanism into the cytosol where they activate the STING pathway leading to Type I-IFN production, and 2) a secondary TLR-2, MyD88 and NFκB dependent signal that enhances Irg1 production independently of Type I IFN induction.