The role of renin-angiotensin-aldosterone system polymorphisms in phenotypic expression of MYBPC3-related hypertrophic cardiomyopathy

The phenotypic variability of hypertrophic cardiomyopathy (HCM) in patients with identical pathogenic mutations suggests additional modifiers. In view of the regulatory role in cardiac function, blood pressure, and electrolyte homeostasis, polymorphisms in the renin-angiotensin-aldosterone system (RAAS) are candidates for modifying phenotypic expression. In order to investigate whether RAAS polymorphisms modulate HCM phenotype, we selected a large cohort of carriers of one of the three functionally equivalent truncating mutations in the MYBPC3 gene. Family-based association analysis was performed to analyze the effects of five candidate RAAS polymorphisms (ACE, rs4646994; AGTR1, rs5186; CMA, rs1800875; AGT, rs699; CYP11B2, rs1799998) in 368 subjects carrying one of the three mutations in the MYBPC3 gene. Interventricular septum (IVS) thickness and Wigle score were assessed by 2D-echocardiography. SNPs in the RAAS system were analyzed separately and combined as a pro-left ventricular hypertrophy (LVH) score for effects on the HCM phenotype. Analyzing the five polymorphisms separately for effects on IVS thickness and Wigle score detected two modest associations. Carriers of the CC genotype in the AGT gene had less pronounced IVS thickness compared with CT and TT genotype carriers. The DD polymorphism in the ACE gene was associated with a high Wigle score (P=0.01). No association was detected between the pro-LVH score and IVS thickness or Wigle score. In conclusion, in contrast to previous studies, in our large study population of HCM patients with functionally equivalent mutations in the MYBPC3 gene we did not find major effects of genetic variation within the genes of the RAAS system on phenotypic expression of HCM

Advances in immersive virtual reality interventions for mental disorders:A new reality?

Immersive virtual reality (VR) has been identified as a potentially revolutionary tool for psychological interventions. This study reviews current advances in immersive VR-based therapies for mental disorders. VR has the potential to make psychiatric treatments better and more cost-effective and to make them available to a larger group of patients. However, this may require a new generation of VR therapeutic techniques that use the full potential of VR, such as embodiment, and self-led interventions. VR-based interventions are promising, but further well-designed studies are needed that use novel techniques and investigate efficacy, efficiency, and cost-effectiveness of VR interventions compared with current treatments. This will be crucial for implementation and dissemination of VR in regular clinical practice

Relations between changes in safety behavior, paranoid ideations, cognitive biases, and clinical characteristics of patients with a psychotic disorder over time

BACKGROUND: Safety behaviors, both positive (maladaptive coping behavior) and negative (avoidance behavior), are used by people with paranoid delusions to avoid perceived threats. Safety behaviors contribute to the persistence of paranoid delusions by preventing disconfirmation of threat beliefs and may influence other psychiatric symptoms. This study investigated how changes in safety behaviors are related to changes in paranoid ideation, social anxiety, depression, cognitive biases and self-esteem over time.METHODS: This study included 116 patients diagnosed with a psychotic disorder (DSM-IV) and at least moderate levels of paranoid ideations (GTPS &gt;40).The data were collected as part of a multi-center randomized controlled trial where patients were randomized to VR-CBT (n = 58) or treatment as usual (TAU; n = 58). Assessments were completed at baseline (T0), after three months (T3) and after six months (T6). For all variables, change scores between T0 and T3 and T3 and T6 were calculated and Pearson correlations between change scores were computed.RESULTS: A decrease in total safety behavior was related to diminished paranoid ideation, social anxiety, and depression. No significant temporal associations were found between changes in safety behavior and changes in cognitive biases and self-esteem. Similar but less robust results were found for respectively negative safety behavior and positive safety behavior.CONCLUSION: Dropping safety behavior can be specifically targeted in behavioral interventions. Whereas there appears to be a relation with reduction in anxiety, paranoia, and depressive symptoms, changes in safety behavior do not seem to align with changes in cognitive thinking processes.</p

COMICS: Cartoon Visualization of Omics Data in Spatial Context Using Anatomical Ontologies

COMICS is an interactive and open-access web platform for integration and visualization of molecular expression data in anatomograms of zebrafish, carp, and mouse model systems. Anatomical ontologies are used to map omics data across experiments and between an experiment and a particular visualization in a data-dependent manner. COMICS is built on top of several existing resources. Zebrafish and mouse anatomical ontologies with their controlled vocabulary (CV) and defined hierarchy are used with the ontoCAT R package to aggregate data for comparison and visualization. Libraries from the QGIS geographical information system are used with the R packages "maps" and "maptools" to visualize and interact with molecular expression data in anatomical drawings of the model systems. COMICS allows users to upload their own data from omics experiments, using any gene or protein nomenclature they wish, as long as CV terms are used to define anatomical regions or developmental stages. Common nomenclatures such as the ZFIN gene names and UniProt accessions are provided additional support. COMICS can be used to generate publication-quality visualizations of gene and protein expression across experiments. Unlike previous tools that have used anatomical ontologies to interpret imaging data in several animal models, including zebrafish, COMICS is designed to take spatially resolved data generated by dissection or fractionation and display this data in visually clear anatomical representations rather than large data tables. COMICS is optimized for ease-of-use, with a minimalistic web interface and automatic selection of the appropriate visual representation depending on the input data.Animal science

Virtual reality cognitive-behavioural therapy versus cognitive-behavioural therapy for paranoid delusions:a study protocol for a single-blind multi-Centre randomised controlled superiority trial

Abstract Background Seventy per cent of patients with psychotic disorders has paranoid delusions. Paranoid delusions are associated with significant distress, hospital admission and social isolation. Cognitive-behavioural therapy for psychosis (CBTp) is the primary psychological treatment, but the median effect size is only small to medium. Virtual reality (VR) has a great potential to improve the effectiveness of CBTp. In a previous study, we found that VR based CBT (VRcbt) for paranoid delusions is superior to waiting list. As a next step, a direct comparison with CBTp is needed. The present study aims to investigate whether VRcbt is more effective and cost-effective than regular CBTp in treating paranoid delusions and improving daily life social functioning of patients with psychotic disorders. Methods A total of 106 patients with DSM-5 diagnosis of psychotic disorder and at least moderate level of paranoid ideations will be recruited for this multicentre randomized controlled trial (RCT). Patients will be randomized to either VRcbt or standard CBTp for paranoid delusions. VRcbt consists of maximum 16 sessions in virtual social situations that trigger paranoid ideations and distress, delivered in an 8–12 week time frame. Standard CBTp also consists of maximum 16 sessions including exposure and behavioural experiments, delivered in an 8–12 week time frame. The two groups will be compared at baseline, post-treatment and six months follow-up. Primary outcome is the level of paranoid ideations in daily life social situations, measured with ecological momentary assessments (EMA) at semi-random moments ten times a day during seven days, before and after treatment. Every session, participants and therapists will rate the level of paranoid ideation and global clinical impression. Discussion Comparison of VRcbt and CBTp will provide information about the relative (cost-) effectiveness of VRcbt for this population. VRcbt may become a preferred psychological treatment for paranoid delusions and social anxiety in patients with psychotic disorder. Trial registration Netherlands Trial Register, NL7758. Registered on 23 May 2019

VIBE: an R-package for VIsualization of Bulk RNA Expression data for therapeutic targeting and disease stratification

BackgroundDevelopment of cancer treatments such as antibody-based therapy relies on several factors across the drug-target axis, including the specificity of target expression and characterization of downstream signaling pathways. While existing tools for analyzing and visualizing transcriptomic data offer evaluation of individual gene-level expression, they lack a comprehensive assessment of pathway-guided analysis, relevant for single- and dual-targeting therapeutics. Here, we introduce VIBE (VIsualization of Bulk RNA Expression data), an R package which provides a thorough exploration of both individual and combined gene expression, supplemented by pathway-guided analyses. VIBE’s versatility proves pivotal for disease stratification and therapeutic targeting in cancer and other diseases.ResultsVIBE offers a wide array of functions that streamline the visualization and analysis of transcriptomic data for single- and dual-targeting therapies. Its intuitive interface allows users to evaluate the expression of target genes and their associated pathways across various cancer indications, aiding in target and disease prioritization. Metadata, such as treatment or number of prior lines of therapy, can be easily incorporated to refine the identification of patient cohorts hypothesized to derive benefit from a given drug. We demonstrate how VIBE can be used to assist in indication selection and target identification in three user case studies using both simulated and real-world data. VIBE integrates statistics in all graphics, enabling data-informed decision-making.ConclusionsVIBE facilitates detailed visualization of individual and cohort-level summaries such as concordant or discordant expression of two genes or pathways. Such analyses can help to prioritize disease indications that are amenable to treatment strategies such as bispecific or monoclonal antibody therapies. With this tool, researchers can enhance indication selection and potentially accelerate the development of novel targeted therapies with the goal of precision, personalization, and ensuring treatments align with an individual patient’s disease state across a spectrum of disorders. Explore VIBE’s full capabilities using the vignettes on the GitLab repository (https://gitlab.com/genmab-public/vibe)

Reporting guidelines for the early-phase clinical evaluation of applications using extended reality: RATE-XR qualitative study guideline

Background: Extended reality (XR), encompassing technologies such as virtual reality, augmented reality, and mixed reality, has rapidly gained prominence in health care. However, existing XR research often lacks rigor, proper controls, and standardization.Objective: To address this and to enhance the transparency and quality of reporting in early-phase clinical evaluations of XR applications, we present the "Reporting for the early-phase clinical evaluation of applications using extended reality" (RATE-XR) guideline.Methods: We conducted a 2-round modified Delphi process involving experts from diverse stakeholder categories, and the RATE-XR is therefore the result of a consensus-based, multistakeholder effort.Results: The guideline comprises 17 XR-specific (composed of 18 subitems) and 14 generic reporting items, each with a complementary Explanation & Elaboration section.Conclusions: The items encompass critical aspects of XR research, from clinical utility and safety to human factors and ethics. By offering a comprehensive checklist for reporting, the RATE-XR guideline facilitates robust assessment and replication of early-stage clinical XR studies. It underscores the need for transparency, patient-centeredness, and balanced evaluation of the applications of XR in health care. By providing an actionable checklist of minimal reporting items, this guideline will facilitate the responsible development and integration of XR technologies into health care and related fields

第776回 千葉医学会例会・第12回 千葉大学放射線医学教室例会 17.

Visualisations of carp organ data. Visualisations that can be used with the supplied R-script. (ZIP 2148 kb

第840回千葉医学会整形外科例会 26.

List of the 89 dissected tissues from 19 organs from adult Carps (1 male, 3 female) and their read counts. Total read count was 512.134.436 averaging ~5.754.320 reads per sample. Additionally two 5 dpf embryos were sampled. (XLSX 12 kb