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Background: Breast cancer is one of the most commonly diagnosed cancers. It is associated with DNA methylation, an epigenetic event with a methyl group added to a cytosine paired with a guanine, i.e., a CG site. The methylation levels of different genes in a genome are correlated in certain ways that affect gene functions. This correlation pattern is known as co-methylation. It is still not clear how different genes co-methylate in the whole genome of breast cancer samples. Previous studies are conducted using relatively small datasets (Illumina 27K data). In this study, we analyze much larger datasets (Illumina 450K data)., Results: Our key findings are summarized below. First, normal samples have more highly correlated, or co-methylated, CG pairs than tumor samples. Both tumor and normal samples have more than 93% positive co-methylation, but normal samples have significantly more negatively correlated CG sites than tumor samples (6.6% vs. 2.8%). Second, both tumor and normal samples have about 94% of co-methylated CG pairs on different chromosomes, but normal samples have 470 million more CG pairs. Highly co-methylated pairs on the same chromosome tend to be close to each other. Third, a small proportion of CG sites' co-methylation patterns change dramatically from normal to tumor. The percentage of differentially methylated (DM) sites among them is larger than the overall DM rate. Fourth, certain CG sites are highly correlated with many CG sites. The top 100 of such super-connector CG sites in tumor and normal samples have no overlaps. Fifth, both highly changing sites and super-connector sites' locations are significantly different from the genome-wide CG sites' locations. Sixth, chromosome X co-methylation patterns are very different from other chromosomes. Finally, the network analyses of genes associated with several sets of co-methylated CG sites identified above show that tumor and normal samples have different patterns., Conclusions: Our findings will provide researchers with a new understanding of co-methylation patterns in breast cancer. Our ability to thoroughly analyze co-methylation of large datasets will allow researchers to study relationships and associations between different genes in breast cancer., (© 2022. The Author(s).)

Patients with chronic pain and especially with craniomandibular disorder (CMD) show specific psychopathology in trait anxiety. In a previous longitudinal functional imaging study on CMD we found that the anterior insula was modulated by successful therapy intervention and pain relief. We here intended to investigate possible associations between anterior insula fMRI-activation during occlusal movements and trait anxiety over a splint therapy approach in patients with CMD. Three fMRI-investigations of a craniomandibular occlusion task were performed together with pain score evaluations and scoring of trait anxiety (State -Trait Anxiety Inventory; STAI) before, after two weeks and after three months of a DIR-mandibular splint therapy in a small group (n = 9) of CMD patients. Patients showed increased anxiety levels before therapy assessed with the STAI and the depression and anxiety scale (DASS). Besides of relevant reduction in pain the STAI decreased over time. Reduction in STAI was associated with anterior insular fMRI-activation reduction on both hemispheres. We conclude that the anxiety driven anticipation of pain related to occlusal trigger is processed in the anterior insula and might therefore be a main driver of therapeutic intervention by the splint therapy in CMD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Behavior performed by parents to assist a youth in avoiding or alleviating anxiety, known as accommodation, is ubiquitous among pediatric anxiety disorders and strongly related to poor treatment outcome. According to cognitive-behavioral theory, the beliefs parents hold regarding accommodation should predict parental accommodating behavior. Unfortunately, little is known about the beliefs parents hold regarding accommodation, as there exists no validated measure of this construct. First, the psychometric properties were examined for the Parental Accommodation Scale (PAS), a novel measure of parental accommodating behavior frequency (PAS-Behavior scale) and parental beliefs about accommodation (PAS-Belief scale). Second, the relationship between parental beliefs about accommodation and accommodation frequency was examined. Results provide preliminary evidence of the internal consistency and convergent validity of the PAS. Stronger positive beliefs about accommodation significantly predicted accommodation frequency, even after controlling for youth anxiety severity. Specifically, beliefs that accommodation prevents youth from losing behavioral and emotional control significantly predicted accommodation frequency. Therefore, efforts to decrease accommodation in clinical settings should involve correcting maladaptive parental beliefs about accommodation, with a particular emphasis on beliefs regarding the necessity of accommodation in preventing a youth from losing behavioral and emotional control., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Body-Focused Repetitive Behaviors (BFRBs), including skin-picking, hair-pulling, and nail-biting, commonly occur in youth, even at elevated/problematic levels, and are associated with a number of other psychiatric symptoms. The present study examined the internal consistency of a brief screening tool for BFRBs as well as the prevalence, severity, and correlates of BFRBs in a sample of youth with a primary anxiety or obsessive-compulsive disorder (OCD)., Methods: Ninety-three youth-parent dyads presenting for treatment for anxiety or OCD completed study measures including the Repetitive Body Focused Behavior Scale - Parent (RBFBS), which includes subscales for skin-picking, hair-pulling, and nail-biting, as well as a number of additional clinician-, parent-, and child-rated scales., Results: The RBFBS demonstrated good to excellent internal consistency. BFRBs were endorsed in 55% of youths, with elevated levels in 27%. Skin-picking was the most common BFRB (38%), followed by nail-biting (34%) and hair-pulling (4%). Youth with BFRBs, as compared to those without, were rated as more avoidant by their parents. Among those with BFRBs, more avoidant tendencies, anxiety sensitivity, and child-rated panic, separation, and generalized anxiety symptoms were associated with elevated BFRB severity. BFRBs were equally common but more likely to be elevated among youth with a primary anxiety, than OCD, diagnosis., Discussion: Results provide initial support for the RBFBS as a brief screening tool for the three common BFRBs. In addition, the results suggest avoidant tendencies and physical manifestations of distress may be particularly relevant to the escalation of BFRB symptoms in youth., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Treatment worries, which surround requirements and results of obtaining treatment, may represent an important construct; however, previous measures were limited by their specificity, format, and lack of parent report. Therefore the present study examined the initial outcomes and psychometrics of corresponding measures of treatment worries in youth (Treatment Worries Questionnaire - Child; TWQ-C) and their parents (Treatment Worries Questionnaire - Parent; TWQ-P). Participants were 94 youth (7-17-years old) and parent dyads presenting for treatment of an anxiety disorder. Dyads completed the TWQ-C and TWQ-P along with additional measures prior to initiating treatment. Treatment worries were endorsed in the mild-moderate range by youth and the TWQ-C demonstrated good-excellent internal consistency, a three-factor structure, and consistent convergent and divergent relationships. Treatment worries were endorsed in the low-mild range by parents and the TWQ-P demonstrated fair-good internal consistency, a four-factor structure, and consistent divergent relationships, but variable (by factor) convergent relationships. The results provide information on treatment worries and support the use of the TWQ-C and TWQ-P as broad assessments of the concept. Low endorsement of worries among parents likely relates to the treatment-seeking nature of the sample. Future investigations using the TWQ-C and TWQ-P in a variety of samples is warranted., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Cognitive-behavioral therapy (CBT) and pharmacotherapy are the most well-established treatments for childhood anxiety disorders. This study examined how parents (N=71) seeking treatment for their child's anxiety disorder perceive the acceptability, believability, and effectiveness of these treatments. While both treatments were perceived favorably, CBT was rated as more acceptable, believable, and effective in the short- and long-term. Children's treatment history influenced parents' perceptions of pharmacotherapy, with parents of children with no treatment history perceiving medication treatment as less acceptable and believable than parents of children with a history of medication alone or in combination with behavior therapy. No effect of treatment history was found for perceptions of CBT. Significant positive correlations emerged between parents' perceived acceptance and believability for pharmacotherapy and child age and level of dysfunction due to their child's anxiety, respectively. The level of the child's anxiety was not significantly correlated with parents' perceptions of either CBT or pharmacotherapy. Our results suggest that parents of anxious children prefer CBT to medication for the treatment of their child's anxiety disorder. Directions for future research are discussed.

This project deals with assessment directives issued by the leading statutory care insurance companies to define the need for care of children at certain ages in coping with the activities of daily life specified by the German Social Legislation. The ages in question relate to healthy, normally developed children. They are used as a measure of comparison for the assessment of diseased children. Besides, they have a decisive significance in defining the need for care. Only if a child is not able to perform a certain activity, although it is meant to be able to do so at that age, can we define the need for help and assistance, i.e. care. The project is divided into two sections. 1. Comparison of age mentioned in the assessment directives for each of the daily life activities of healthy and normally developed children aged 1 to 12 years with the age mentioned in technical literature. 2. Comparison of age mentioned in the assessment directives for each ot the daily life activities of healthy and normally developed children at the age of 1 to 12 years with those mentioned in retrospective interviews with the same group of children. In the first part of the project, an analysis of the literature dealing with the subject was done. The literature included the stock of technical literature in the German language. Studying the literature, ages for children could be isolated, that could be classed with the activities of daily life mentioned in the German Social Code. These ages were compared with those in the assessment directives. In a second part of the project, 81 mothers and fathers of healthy, normally developed children aged 1 to 12 years were asked via a questionnaire. They were asked to estimate retrospectively from what age on their child had been able to perform certain activities of daily life without any help. The comparison of ages mentioned in the assessment directives with those of the analysis of literature conformed only regarding daily life activity. Regarding the other activities of daily life the age for children was set higher in the assessment directives than in the literature. Comparing the age of children in the assessment directives with the results of the questionnaires the age was also set higher in the directives than shown by the results of the questionnaires. The results of the literature analysis and the inquiry by questionnaires show that the ages mentioned in the assessment directives for an independent performance of daily life activities do not correspond to the development according to the age of healthy normally developed children aged 1 to 12 years. As a result of this project it seems to be justified to be doubtful about an adequate assessment of children who are in the need of care. Due to this reason it would be desirable to reexamine the data of the assessment directives by means of a new representative prospective study.