Social communication between virtual characters and children with autism

Children with ASD have difficulty with social communication, particularly joint attention. Interaction in a virtual environment (VE) may be a means for both understanding these difficulties and addressing them. It is first necessary to discover how this population interacts with virtual characters, and whether they can follow joint attention cues in a VE. This paper describes a study in which 32 children with ASD used the ECHOES VE to assist a virtual character in selecting objects by following the character’s gaze and/or pointing. Both accuracy and reaction time data suggest that children were able to successfully complete the task, and qualitative data further suggests that most children perceived the character as an intentional being with relevant, mutually directed behaviour

Making & Sustaining Change from Psychotherapy: A Mixed Method Study

This mixed method study explored both (1) how changes are made and (2) what encourages the maintenance of change after psychotherapy. Literature has called for further exploration into what helps clients to make and sustain change from their perspectives. While the effectiveness of approaches such as: psychodynamic, cognitive behavioral, and other disorder-specific treatments has been demonstrated broadly, less is known about individual variables, and specifically about how individuals participate in and support their recovery. This study used a mixed method sequential design. Wampold & Imel’s (2015) contextual model was used as a conceptual framework throughout the study. Using secondary data analysis, we used quantitative methods to explore the degree to which clients made and maintained progress using an empirical measure: the OQ-45.2 (using a longitudinal, within subjects design). Fourteen (N = 14) qualitative interviews were reviewed to hear from a sample of former clients about their impressions of what supported their efforts at change and how they maintained these gains 12–18 months post treatment. The findings of the quantitative strand demonstrated clinically meaningful change from pretest to posttest, posttest to follow-up, and from pretest to follow-up with an effect size of d = .5. Qualitative themes emerged within five categories used to describe the findings. These categories included questions asking about: (1) what drives or facilitates change, (2) what participants do to maintain change post-therapy, and (3) what was and was not helpful in their therapy experiences. The findings suggest implications for both practice and policy. Practice implications include the importance of both monitoring client progress and of termination as a distinct phases of therapeutic relationships. Policy implications include the importance of economic and other macro-level variables in supporting or discouraging mental health

Making & Sustaining Change from Psychotherapy: A Mixed Method Study

This mixed method study explored both (1) how changes are made and (2) what encourages the maintenance of change after psychotherapy. Literature has called for further exploration into what helps clients to make and sustain change from their perspectives. While the effectiveness of approaches such as: psychodynamic, cognitive behavioral, and other disorder-specific treatments has been demonstrated broadly, less is known about individual variables, and specifically about how individuals participate in and support their recovery. This study used a mixed method sequential design. Wampold & Imel’s (2015) contextual model was used as a conceptual framework throughout the study. Using secondary data analysis, we used quantitative methods to explore the degree to which clients made and maintained progress using an empirical measure: the OQ-45.2 (using a longitudinal, within subjects design). Fourteen (N = 14) qualitative interviews were reviewed to hear from a sample of former clients about their impressions of what supported their efforts at change and how they maintained these gains 12–18 months post treatment. The findings of the quantitative strand demonstrated clinically meaningful change from pretest to posttest, posttest to follow-up, and from pretest to follow-up with an effect size of d = .5. Qualitative themes emerged within five categories used to describe the findings. These categories included questions asking about: (1) what drives or facilitates change, (2) what participants do to maintain change post-therapy, and (3) what was and was not helpful in their therapy experiences. The findings suggest implications for both practice and policy. Practice implications include the importance of both monitoring client progress and of termination as a distinct phases of therapeutic relationships. Policy implications include the importance of economic and other macro-level variables in supporting or discouraging mental health

Differential hepatitis C virus RNA target site selection and host factor activities of naturally occurring miR-122 3′ variants

In addition to suppressing cellular gene expression, certain miRNAs potently facilitate replication of specific positive-strand RNA viruses. miR-122, a pro-viral hepatitis C virus (HCV) host factor, binds and recruits Ago2 to tandem sites (S1 and S2) near the 5΄ end of the HCV genome, stabilizing it and promoting its synthesis. HCV target site selection follows canonical miRNA rules, but how non-templated 3΄ miR-122 modifications impact this unconventional miRNA action is unknown. High-throughput sequencing revealed that a 22 nt miRNA with 3΄G (‘22–3΄G’) comprised <63% of total miR-122 in human liver, whereas other variants (23–3΄A, 23–3΄U, 21–3΄U) represented 11–17%. All loaded equivalently into Ago2, and when tested individually functioned comparably in suppressing gene expression. In contrast, 23–3΄A and 23–3΄U were more active than 22–3΄G in stabilizing HCV RNA and promoting its replication, whereas 21–3΄U was almost completely inactive. This lack of 21–3΄U HCV host factor activity correlated with reduced recruitment of Ago2 to the HCV S1 site. Additional experiments demonstrated strong preference for guanosine at nt 22 of miR-122. Our findings reveal the importance of non-templated 3΄ miR-122 modifications to its HCV host factor activity, and identify unexpected differences in miRNA requirements for host gene suppression versus RNA virus replication

Locus Coeruleus Activation Facilitates Memory Encoding and Induces Hippocampal LTD that Depends on β-Adrenergic Receptor Activation

Spatial memory formation is enabled through synaptic information processing, in the form of persistent strengthening and weakening of synapses, within the hippocampus. It is, however, unclear how relevant spatial information is selected for encoding, in preference to less pertinent information. As the noradrenergic locus coeruleus (LC) becomes active in response to novel experiences, we hypothesized that the LC may provide the saliency signal required to promote hippocampal encoding of relevant information through changes in synaptic strength. Test pulse stimulation evoked stable basal synaptic transmission at Schaffer collateral (SC)–CA1 stratum radiatum synapses in freely behaving adult rats. Coupling of these test pulses with electrical stimulation of the LC induced long-term depression (LTD) at SC–CA1 synapses and induced a transient suppression of theta-frequency oscillations. Effects were N-methyl-D-aspartate and β-adrenergic receptor dependent. Activation of the LC also increased CA1 noradrenalin levels and facilitated the encoding of spatial memory for a single episode via a β-adrenoceptor–dependent mechanism. Our results demonstrate that the LC plays a key role in the induction of hippocampal LTD and in promoting the encoding of spatial information. This LC–hippocampal interaction may reflect a means by which salient information is distinguished for subsequent synaptic processing

Functionally conserved architecture of hepatitis C virus RNA genomes

Plus-sense RNA viruses cause diverse pathologies in humans. Viral RNA genomes are selected to encode information both in their primary sequences and in their higher-order tertiary structures required to replicate and to evade host immune responses. We interrogated the physical structures of three evolutionarily divergent hepatitis C virus (HCV) RNA genomes using high-throughput chemical probing and found, along with all previously known RNA-structure–based regulatory elements, diverse previously uncharacterized structures that impact viral replication. We also characterized strategies by which the HCV genomic RNA structure masks detection by innate immune sensors. This structure-first strategy for comparative analysis of genome-wide RNA structure can be broadly applied to understand the contributions of higher-order genome structure to viral replication and pathogenicity

microRNA-122 Abundance in Hepatocellular Carcinoma and Non-Tumor Liver Tissue from Japanese Patients with Persistent HCV versus HBV Infection

Mechanisms of hepatic carcinogenesis in chronic hepatitis B and hepatitis C are incompletely defined but often assumed to be similar and related to immune-mediated inflammation. Despite this, several studies hint at differences in expression of miR-122, a liver-specific microRNA with tumor suppressor properties, in hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) versus hepatitis C virus (HCV) infection. Differences in the expression of miR-122 in these cancers would be of interest, as miR-122 is an essential host factor for HCV but not HBV replication. To determine whether the abundance of miR-122 in cancer tissue is influenced by the nature of the underlying virus infection, we measured miR-122 by qRT-PCR in paired tumor and non-tumor tissues from cohorts of HBV- and HCV-infected Japanese patients. miR-122 abundance was significantly reduced from normal in HBV-associated HCC, but not in liver cancer associated with HCV infection. This difference was independent of the degree of differentiation of the liver cancer. Surprisingly, we also found significant differences in miR-122 expression in non-tumor tissue, with miR-122 abundance reduced from normal in HCV- but not HBV-infected liver. Similar differences were observed in HCV- vs. HBV-infected chimpanzees. Among HCV-infected Japanese subjects, reductions in miR-122 abundance in non-tumor tissue were associated with a single nucleotide polymorphism near the IL28B gene that predicts poor response to interferon-based therapy (TG vs. TT genotype at rs8099917), and correlated negatively with the abundance of multiple interferon-stimulated gene transcripts. Reduced levels of miR-122 in chronic hepatitis C thus appear to be associated with endogenous interferon responses to the virus, while differences in miR-122 expression in HCV- versus HBV-associated HCC likely reflect virus-specific mechanisms contributing to carcinogenesis. The continued expression of miR-122 in HCV-associated HCC may signify an important role for HCV replication late in the progression to malignancy

Blending human and artificial intelligence to support autistic children’s social communication skills

This paper examines the educational efficacy of a learning environment in which children diagnosed with Autism Spectrum Conditions (ASC) engage in social interactions with an artificially intelligent (AI) virtual agent and where a human practitioner acts in support of the interactions. A multi-site intervention study in schools across the UK was conducted with 29 children with ASC and learning difficulties, aged 4-14 years old. For reasons related to data completeness and amount of exposure to the AI environment, data for 15 children was included in the analysis. The analysis revealed a significant increase in the proportion of social responses made by ASC children to human practitioners. The number of initiations made to human practitioners and to the virtual agent by the ASC children also increased numerically over the course of the sessions. However, due to large individual differences within the ASC group, this did not reach significance. Although no evidence of transfer to the real-world post-test was shown, anecdotal evidence of classroom transfer was reported. The work presented in this paper offers an important contribution to the growing body of research in the context of AI technology design and use for autism intervention in real school contexts. Specifically, the work highlights key methodological challenges and opportunities in this area by leveraging interdisciplinary insights in a way that (i) bridges between educational interventions and intelligent technology design practices, (ii) considers the design of technology as well as the design of its use (context and procedures) on par with one another, and (iii) includes design contributions from different stakeholders, including children with and without ASC diagnosis, educational practitioners and researchers

Transcriptomic Analysis of Chronic Hepatitis B and C and Liver Cancer Reveals MicroRNA-Mediated Control of Cholesterol Synthesis Programs

ABSTRACT Chronic hepatitis B (CHB), chronic hepatitis C (CHC), and associated hepatocellular carcinoma (HCC) are characterized by cholesterol imbalance and dyslipidemia; however, the key regulatory drivers of these phenotypes are incompletely understood. Using gene expression microarrays and high-throughput sequencing of small RNAs, we performed integrative analysis of microRNA (miRNA) and gene expression in nonmalignant and matched cancer tissue samples from human subjects with CHB or CHC and HCC. We also carried out follow-up functional studies of specific miRNAs in a cell-based system. These studies led to four major findings. First, pathways affecting cholesterol homeostasis were among the most significantly overrepresented among genes dysregulated in chronic viral hepatitis and especially in tumor tissue. Second, for each disease state, specific miRNA signatures that included miRNAs not previously associated with chronic viral hepatitis, such as miR-1307 in CHC, were identified. Notably, a few miRNAs, including miR-27 and miR-224, were components of the miRNA signatures of all four disease states: CHB, CHC, CHB-associated HCC, and CHC-associated HCC. Third, using a statistical simulation method (miRHub) applied to the gene expression data, we identified candidate master miRNA regulators of pathways controlling cholesterol homeostasis in chronic viral hepatitis and HCC, including miR-21, miR-27, and miR-33. Last, we validated in human hepatoma cells that both miR-21 and miR-27 significantly repress cholesterol synthesis and that miR-27 does so in part through regulation of the gene that codes for the rate-limiting enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase ( HMGCR ). IMPORTANCE Hepatitis B virus (HBV) and hepatitis C virus (HCV) are phylogenetically unrelated hepatotropic viruses that persistently infect hundreds of millions of people world-wide, often leading to chronic liver disease and hepatocellular carcinoma (HCC). Chronic hepatitis B (CHB), chronic hepatitis C (CHC), and associated HCC often lead to cholesterol imbalance and dyslipidemia. However, the regulatory mechanisms underlying the dysregulation of lipid pathways in these disease states are incompletely understood. MicroRNAs (miRNAs) have emerged as critical modulators of lipid homeostasis. Here we use a blend of genomic, molecular, and biochemical strategies to identify key miRNAs that drive the lipid phenotypes of chronic viral hepatitis and HCC. These findings provide a panoramic view of the miRNA landscape in chronic viral hepatitis, which could contribute to the development of novel and more-effective miRNA-based therapeutic strategies

Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C

Persistent infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) account for the majority of cases of hepatic cirrhosis and hepatocellular carcinoma (HCC) worldwide. Small, non-coding RNAs play important roles in virus-host interactions. We used high throughput sequencing to conduct an unbiased profiling of small (14-40 nts) RNAs in liver from Japanese subjects with advanced hepatitis B or C and hepatocellular carcinoma (HCC). Small RNAs derived from tRNAs, specifically 30–35 nucleotide-long 5′ tRNA-halves (5′ tRHs), were abundant in non-malignant liver and significantly increased in humans and chimpanzees with chronic viral hepatitis. 5′ tRH abundance exceeded microRNA abundance in most infected non-cancerous tissues. In contrast, in matched cancer tissue, 5′ tRH abundance was reduced, and relative abundance of individual 5′ tRHs was altered. In hepatitis B-associated HCC, 5′ tRH abundance correlated with expression of the tRNA-cleaving ribonuclease, angiogenin. These results demonstrate that tRHs are the most abundant small RNAs in chronically infected liver and that their abundance is altered in liver cancer