Encoding edge type information in graphlets.

Graph embedding approaches have been attracting increasing attention in recent years mainly due to their universal applicability. They convert network data into a vector space in which the graph structural information and properties are maximumly preserved. Most existing approaches, however, ignore the rich information about interactions between nodes, i.e., edge attribute or edge type. Moreover, the learned embeddings suffer from a lack of explainability, and cannot be used to study the effects of typed structures in edge-attributed networks. In this paper, we introduce a framework to embed edge type information in graphlets and generate a Typed-Edge Graphlets Degree Vector (TyE-GDV). Additionally, we extend two combinatorial approaches, i.e., the colored graphlets and heterogeneous graphlets approaches to edge-attributed networks. Through applying the proposed method to a case study of chronic pain patients, we find that not only the network structure of a patient could indicate his/her perceived pain grade, but also certain social ties, such as those with friends, colleagues, and healthcare professionals, are more crucial in understanding the impact of chronic pain. Further, we demonstrate that in a node classification task, the edge-type encoded graphlets approaches outperform the traditional graphlet degree vector approach by a significant margin, and that TyE-GDV could achieve a competitive performance of the combinatorial approaches while being far more efficient in space requirements

Using manipulated photographs to identify features of streetscapes that may encourage older adults to walk for transport

Experimental evidence of environmental features important for physical activity is challenging to procure in real world settings. The current study aimed to investigate the causal effects of environmental modifications on a photographed street\u27s appeal for older adults\u27 walking for transport. Secondly, we examined whether these effects differed according to gender, functional limitations, and current level of walking for transport. Thirdly, we examined whether different environmental modifications interacted with each other. Qualitative responses were also reported to gain deeper insight into the observed quantitative relationships. Two sets of 16 panoramic photographs of a streetscape were created, in which six environmental factors were manipulated (sidewalk evenness, traffic level, general upkeep, vegetation, separation from traffic, and benches). Sixty older adults sorted these photographs on appeal for walking for transport on a 7-point scale and reported qualitative information on the reasons for their rankings. Sidewalk evenness appeared to have the strongest influence on a street\u27s appeal for transport-related walking. The effect of sidewalk evenness was even stronger when the street\u27s overall upkeep was good and when traffic was absent. Absence of traffic, presence of vegetation, and separation from traffic also increased a street\u27s appeal for walking for transport. There were no moderating effects by gender or functional limitations. The presence of benches increased the streetscape\u27s appeal among participants who already walked for transport at least an hour/week. The protocols and methods used in the current study carry the potential to further our understanding of environment-PA relationships. Our findings indicated sidewalk evenness as the most important environmental factor influencing a street\u27s appeal for walking for transport among older adults. However, future research in larger samples and in real-life settings is needed to confirm current findings

Epigenetic editing:towards realization of the curable genome concept

Recent developments in biotechnology have enabled scientists to modulate DNA sequences in a precise way. These genome engineering technologies also open new possibilities to alter the epigenetic composition of the genome at any given genomic location thereby changing gene expression patterns, while leaving the primary DNA sequence intact. This new approach, so-called epigenetic editing, holds great promise to permanently reprogram cell identity. As reprogramming the epigenetic composition, and hence gene expression patterns is now technically feasible, the society needs to consider to what extent interference at the epigenetic level can be accepted. In this review, we discuss the potential epigenetic editing holds for research and therapy, and also touch upon societal implications of this rapidly growing research field

Acceptance, well-being, and goals in adolescents with chronic illness : a daily process analysis

Objective: The main aim of this study was to investigate the relationship between acceptance and well-being in adolescents with chronic illness from a daily process perspective. Furthermore, we explored the role of daily experienced interference and facilitation of life goals by treatment goals as mediating mechanisms. Methods: Thirty-eight adolescents with cystic fibrosis (CF) or diabetes completed questionnaires assessing acceptance, negative life events and goal-related self-efficacy. Furthermore, an online diary assessing daily mood, daily experienced interference and facilitation of life goals by treatment goals was completed during three consecutive weeks. Results: Acceptance of illness was positively related to daily well-being, but unrelated to daily goal interference and facilitation. Furthermore, daily goal interference and facilitation were unrelated to same-day and next-day well-being. Conclusion: This study suggests that acceptance of illness plays an important role in the daily mood of adolescents with CF and diabetes. This relationship, however, was not mediated by daily experienced interference and facilitation of life goals by treatment goals. Further research is needed to determine whether interventions promoting acceptance are beneficial for adolescents with CF and diabetes

Targeted epigenetic editing of SPDEF reduces mucus production in lung epithelial cells

Airway mucus hypersecretion contributes to the morbidity and mortality in patients with chronic inflammatory lung diseases. Reducing mucus production is crucial for improving patients' quality of life. The transcription factor SAM-pointed domain-containing Ets-like factor (SPDEF) plays a critical role in the regulation of mucus production and, therefore, represents a potential therapeutic target. This study aims to reduce lung epithelial mucus production by targeted silencing SPDEF using the novel strategy, epigenetic editing. Zinc fingers and CRISPR/dCas platforms were engineered to target repressors (KRAB, DNA methyltransferases, histone methyltransferases) to the SPDEF promoter. All constructs were able to effectively suppress both SPDEF mRNA and protein expression, which was accompanied by inhibition of downstream mucus-related genes [anterior gradient 2 (AGR2), mucin 5AC (MUC5AC)]. For the histone methyltransferase G9A, and not its mutant or other effectors, the obtained silencing was mitotically stable. These results indicate efficient SPDEF silencing and downregulation of mucus-related gene expression by epigenetic editing, in human lung epithelial cells. This opens avenues for epigenetic editing as a novel therapeutic strategy to induce long-lasting mucus inhibition

Personality and Temperament Correlates of Pain Catastrophizing in Young Adolescents

Pain catastrophizing is generally viewed as an important cognitive factor underlying chronic pain. The present study examined personality and temperament correlates of pain catastrophizing in a sample of young adolescents (N = 132). Participants completed the Pain Catastrophizing Scale for Children, as well as scales for measuring sensitivity of the behavioral inhibition and behavioral activation systems (BIS-BAS), and various reactive and regulative temperament traits. Results demonstrated that BIS, reactive temperament traits (fear and anger-frustration), and perceptual sensitivity were positively related to pain catastrophizing, whereas regulative traits (attention control, inhibitory control) were negatively associated with this cognitive factor. Further, regression analyses demonstrated that only BIS and the temperamental traits of fear and perceptual sensitivity accounted for a unique proportion of the variance in adolescents’ pain catastrophizing scores

Working with pain : sustainable work participation of workers with chronic nonspecific musculoskeletal pain

Dit proefschrift is een van de eerste studies specifiek gericht op mensen die blijven werken met chronische pijn aan het bewegingsapparaat. Unieke kennis over duurzame arbeidsparticipatie van werknemers met chronische pijn werd vergaard. Doel van dit promotieonderzoek was meer inzicht te krijgen in de groep mensen die werkt met pijn en te achterhalen hoe zij in staat zijn ondanks hun klachten te blijven werken. In het proefschrift staan kenmerken en determinanten beschreven van werknemers die doorwerken met chronische pijn, waardoor een completer beeld is ontstaan van arbeidsparticipatie bij mensen met chronische pijn aan het bewegingsapparaat. Uit de vergelijking van mensen die doorwerken ondanks chronische pijn en mensen met arbeidsverzuim die in revalidatiebehandeling komen met chronische pijn blijkt dat deze groepen op diverse factoren significant verschillen. In het onderzoek werd onder andere aangetoond dat de motivatie voor werk, zelfmanagementvaardigheden en het belang dat wordt toegekend aan pijn, belangrijke factoren zijn die werken met chronische pijn faciliteren. Chronische pijn op zichzelf is vaak niet de reden voor arbeidsverzuim, maar meestal spelen persoonlijke- en omgevingsfactoren daarin een beslissende rol. Deze factoren kunnen dienen als aangrijpingspunt voor het verhogen van duurzame inzetbaarheid en preventie van arbeidsverzuim van mensen met chronische pijn aan het bewegingsapparaat. De effectieve manier waarop deelnemende werknemers in het onderzoek met hun pijn omgingen en productief bleven, kan anderen inspireren aan het werk te blijven. Daarnaast biedt het onderzoek een nieuw referentiekader voor de bedrijfs-, verzekerings-, en revalidatiegeneeskunde. This thesis was one of the first studies that focused specifically on people who continued work with chronic nonspecific musculoskeletal pain (CMP), and collected (identified) unique data concerning sustainable work participation of workers with CMP. It provides a large range of characteristics of workers with CMP who continued work despite pain, which has added to our understanding of sustainable work participation in people suffering from CMP. Comparison of workers who continued work with CMP with sick listed workers with CMP admitted for rehabilitation revealed that these groups differ significantly on several factors. In this thesis, evidence was found that the workers’ motivation to work, self-management skills, and the attributed importance of pain on their (working) lives are important factors to manage staying at work with CMP. It is recommended to be aware of the fact that CMP standing on itself is often not the reason for sick leave and disability, but regularly personal and environmental factors play an additional decisive role. Because these factors can be influenced, they offer opportunity to promote staying at work. In the process of guiding workers back to work, the results of the project ‘Working with pain’ may be used. The findings of this thesis potentially contribute to promotion of sustained work participation and prevention of sick-leave in workers with CMP. The effective way workers in this project coped with CMP and remained productive, may inspire others in their efforts to stay work. Finally, this thesis offers a new reference for rehabilitation-, occupational-,and insurance medicine.

Computed tomographic analysis of the quality of trunk muscles in asymptomatic and symptomatic lumbar discectomy patients

Background: No consensus exists on how rehabilitation programs for lumbar discectomy patients with persistent complaints after surgery should be composed. A better understanding of normal and abnormal postoperative trunk muscle condition might help direct the treatment goals. Methods: A three-dimensional CT scan of the lumbar spine was obtained in 18 symptomatic and 18 asymptomatic patients who had undergone a lumbar discectomy 42 months to 83 months (median 63 months) previously. The psoas muscle (PS), the paraspinal muscle mass (PA) and the multifidus muscle (MF) were outlined at the L3, L4 and L5 level. Of these muscles, fat free Cross Sectional Area (CSA) and fat CSA were determined. CSA of the lumbar erector spinae (LES = longissimus thoracis + iliocostalis lumborum) was calculated by subtracting MF CSA from PA CSA. Mean muscle CSA of the left and right sides was calculated at each level. To normalize the data for interpersonal comparison, the mean CSA was divided by the CSA of the L3 vertebral body (mCSA = normalized fat-free muscle CSA; fCSA = normalized fat CSA). Differences in CSA between the pain group and the pain free group were examined using a General Linear Model (GLM). Three levels were examined to investigate the possible role of the level of operation. Results: In lumbar discectomy patients with pain, the mCSA of the MF was significantly smaller than in pain-free subjects (p = 0.009) independently of the level. The mCSA of the LES was significantly smaller in pain patients, but only on the L3 slice (p = 0.018). No significant difference in mCSA of the PS was found between pain patients and pain-free patients (p = 0.462). The fCSA of the MF (p = 0.186) and of the LES (p = 0.256) were not significantly different between both populations. However, the fCSA of the PS was significantly larger in pain patients than in pain-free patients. (p = 0.012). The level of operation was never a significant factor. Conclusions: CT comparison of MF, LES and PS muscle condition between lumbar discectomy patients without pain and patients with protracted postoperative pain showed a smaller fat-free muscle CSA of the MF at all levels examined, a smaller fat-free muscle CSA of the LES at the L3 level, and more fat in the PS in patients with pain. The level of operation was not found to be of importance. The present results suggest a general lumbar muscle dysfunction in the pain group, in particular of the deep stabilizing muscle system