Refine
Language
- English (7)
Has Fulltext
- yes (7)
Is part of the Bibliography
- no (7)
Keywords
- App (1)
- App-based treatment (1)
- COVID-19 pandemic (1)
- Cognitive behavioral therapy (1)
- EP300 (1)
- EWSR1 (1)
- FOXO1 (1)
- Fear of infection (1)
- Gene fusion (1)
- Germ aversion (1)
Institute
Epigenetic neural glioblastoma enhances synaptic integration and predicts therapeutic vulnerability
(2023)
Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals high abundance of stem cell-like malignant cells classified as oligodendrocyte precursor and neural precursor cell-like in high-neural glioblastoma. High-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.
Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.
The COVID-19 pandemic has called worldwide for strong governmental measures to contain its spread, associated with considerable psychological distress. This study aimed at screening a convenience sample in Germany during lockdown for perceived vulnerability to disease, knowledge about COVID-19, symptoms of depression and anxiety, and behavioral responses. In an online survey, 1358 participants completed the perceived vulnerability to disease scale (PVD), the Patient Health Questionnaire (PHQ-4), and questionnaires on knowledge about COVID-19 and self-perceived change in behaviors in response to COVID-19. Lower and upper quartiles of the PVD were used to classify individuals into low and high PVD. A confirmatory factor analysis supported three factors representing risk, preventive and adaptive behavior as behavioral responses to COVID-19 lockdown. A structural equation model showed that the score of the knowledge scale significantly predicted the self-reported increase in adaptive and preventive behavior. The score in the PVD-subscale Perceived Infectability predicted a self-reported increase in preventive behavior, whereas the Germ Aversion score predicted a self-reported increase in preventive and a decrease in risk behavior. The score in PHQ-4 predicted a higher score in the perceived infectability and germ aversion subscales, and a self-reported decrease in adaptive behavior. Low-, medium- and high-PVD groups reported distinct patterns of behavior, knowledge, and mental health symptoms. This study shows that perceived vulnerability to disease is closely linked to preventive behaviors and may enhance adaptation to COVID-19 pandemic.
Social pain is an emotional reaction to social exclusion which has been widely investigated in experimental settings. We developed the Social Pain Questionnaire (SPQ) and examined its factor structure, reliability, and construct validity. We constructed a 46-item pool that covered a broad range of situations related to social pain. Using three different subsamples (Online convenience sample: n = 623, Representative sample: n = 2531, Clinical sample of outpatients seeking psychotherapy: n = 270) we reduced the item pool to 10 items for the final SPQ scale, paying particular attention to content validity and factorial structure. Convergent, divergent and discriminant validity were assessed using standardized measures of related constructs and group differences. For the final 10-item version, a good factorial structure and reliability were found. Convergent validity was supported by correlations with related instruments of interpersonal sensitivity, attachment styles, depression and social anxiety. The representative and clinical sample differed significantly in social pain. The SPQ is an economic self-report measure with solid psychometric properties. Our data support the factorial, construct and convergent validity. The SPQ can be used to clarify the role of social pain in mental disorders and to incorporate interventions targeted towards social pain in psychotherapeutic settings.
Background:
There is growing evidence that Internet-based cognitive behavioral therapy (ICBT) is as effective as a stand-alone treatment and helps facilitating access to treatment. Given the complexity of the treatment, we argue that the effect of ICBT could be even greater if guided by a therapist, as this could increase treatment adherence. We modified an established and well-evaluated treatment approach and developed a mobile application for treating social anxiety disorder (SAD). In the present study, we compare the efficacy of app use alone (APP) with video-based, therapist-guided app use (TG-APP) and with a wait-list control group (WLC) in terms of symptom reduction, and various secondary outcomes such as increase in quality of life or decrease of general psychological distress.
Methods/design:
A within-between interaction design with randomization to one of three conditions will be used. In the APP condition, patients receive only the app without any additional contact with therapists, while in the TG-APP condition, therapists provide 8 sessions of video-based treatment in addition to using the app. The study will be conducted in two university outpatient treatment centers with reliably diagnosed SAD patients. The primary outcome will be defined as change in SAD symptoms, as measured by the Liebowitz Social Anxiety Scale (expert rating). Furthermore, a wide range of self-reports and clinician ratings for other symptoms (depression, general psychopathology) or quality of life will be used. A simulation-based power analysis for a 3 × 2 interaction effect (group × time) on the primary outcome in a linear mixed model resulted in a total sample size of N = 165.
Discussion:
The present study will be one of the first to examine the additional benefit of therapist-guided video sessions regarding the use of an app treating SAD. Study results are pivotal to future treatment application in SAD.