Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined time intervals) in comparison to the continuous delivery of interventions. Methods: We randomly assigned 93 participants to the continuous delivery (CD) or burst delivery (BD) group. The CD group engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule that provides five prompts per day throughout the 3-week-long study, while the BD group received five daily prompts only in the first and third weeks of the study. Results: No significant differences were found between the groups in terms of adherence, mental health outcomes (specifically depressive and anxiety symptoms), level of perceived stress, and perceived helpfulness of intervention. The BD group showed a significantly decreased perceived difficulty of intervention over time. Conclusions: The results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it improved the feasibility of the positive cognitive reappraisal intervention without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research.
BACKGROUND: The mobile Agnew Relationship Measure (mARM) is a self-report questionnaire for the evaluation of digital mental health interventions and their interactions with users. With the global increase in digital mental health intervention research, translated measures are required to conduct research with local populations. OBJECTIVE: The aim of this study was to translate and validate the original English version of the mARM into a German version (mARM-G). METHODS: A total of 2 native German speakers who spoke English as their second language conducted forward translation of the original items. This version was then back translated by 2 native German speakers with a fluent knowledge of English. An independent bilingual reviewer then compared these drafts and created a final German version. The mARM-G was validated by 15 experts in the field of mobile app development and 15 nonexperts for content validity and face validity; 144 participants were recruited to conduct reliability testing as well as confirmatory factor analysis. RESULTS: The content validity index of the mARM-G was 0.90 (expert ratings) and 0.79 (nonexperts). The face validity index was 0.89 (experts) and 0.86 (nonexperts). Internal consistency for the entire scale was Cronbach α=.91. Confirmatory factor analysis results were as follows: the chi-square statistic to df ratio was 1.66. Comparative Fit Index was 0.87 and the Tucker-Lewis Index was 0.86. The root mean square error of approximation was 0.07. CONCLUSIONS: The mARM-G is a valid and reliable tool that can be used for future studies in German-speaking countries.
Knowledge , Language , Humans , Reproducibility of Results , Factor Analysis, Statistical , Mental Health
Robust reward sensitivity may help preserve mental well-being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, "Imager," which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two-arm randomized controlled trial with 95 participants screened for reward sensitivity. Participants in the intervention group received an ecological momentary intervention-Imager, which encouraged participants to create mental images of rewarding events for 1 week. The control group participants received only ecological momentary assessment, without the instruction to generate mental images. Adherence to Imager was high; participants in the intervention group engaged in 88% of the planned activities. In the follow-up assessment, the intervention group reported less mental health symptoms, mainly in depression (ß = -0.34, df = 93, p = .004) and less perceived stress (ß = -0.18, df = 93, p = .035), than control group participants and compared with the baseline assessment. Our results show the positive effects of Imager on mental health symptoms. The encouraging effects of the app on mental health outcomes may lead to greater use of ecological momentary interventions in the clinical preventive practice of affective disorders.
BACKGROUND: Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low "stressor reactivity" [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. OBJECTIVE: Extending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. METHODS: Over 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. RESULTS: RFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P<.001) but also prospectively (average SR scores across subsequent weeks; positive appraisal (PA), P=.008; OPT, P<.001; GSE, P=.01; REC, P<.001; and PSS, P=.002). In both associations, PAS mediated the effects of PSS on SR (cross-sectionally: 95% CI -0.064 to -0.013; prospectively: 95% CI -0.074 to -0.0008). In the analyses of weekly RF-SR dynamics, the RFs PA of stressors generally and specifically related to the COVID-19 pandemic, and GSE were negatively associated with SR in a contemporaneous fashion (PA, P<.001; PAC,P=.03; and GSE, P<.001), but not in a lagged fashion (PA, P=.36; PAC, P=.52; and GSE, P=.06). CONCLUSIONS: We identified psychological RFs that prospectively predict resilience and cofluctuate with weekly SR within individuals. These prospective results endorse that the previously reported RF-SR associations do not exclusively reflect mood congruency or other temporal bias effects. We further confirm the important role of PA in resilience.
BACKGROUND: Digital tools assessing momentary parameters and offering interventions in people's daily lives play an increasingly important role in mental health research and treatment. Ecological momentary assessment (EMA) makes it possible to assess transient mental health states and their parameters. Ecological momentary interventions (EMIs) offer mental health interventions that fit well into individuals' daily lives and routines. Self-efficacy is a transdiagnostic construct that is commonly associated with positive mental health outcomes. OBJECTIVE: The aim of our study assessing mood, specific self-efficacy, and other parameters using EMA was 2-fold. First, we wanted to determine the effects of daily assessed moods and dissatisfaction with social contacts as well as the effects of baseline variables, such as depression, on specific self-efficacy in the training group (TG). Second, we aimed to explore which variables influenced both groups' positive and negative moods during the 7-day study period. METHODS: In this randomized controlled trial, we applied digital self-efficacy training (EMI) to 93 university students with elevated self-reported stress levels and daily collected different parameters, such as mood, dissatisfaction with social contacts, and specific self-efficacy, using EMA. Participants were randomized to either the TG, where they completed the self-efficacy training combined with EMA, or the control group, where they completed EMA only. RESULTS: In total, 93 university students participated in the trial. Positive momentary mood was associated with higher specific self-efficacy in the evening of the same day (b=0.15, SE 0.05, P=.005). Higher self-efficacy at baseline was associated with reduced negative mood during study participation (b=-0.61, SE 0.30, P=.04), while we could not determine an effect on positive mood. Baseline depression severity was significantly associated with lower specific self-efficacy over the week of the training (b=-0.92, SE 0.35, P=.004). Associations between higher baseline anxiety with higher mean negative mood (state anxiety: b=0.78, SE 0.38, P=.04; trait anxiety: b=0.73, SE 0.33, P=.03) and lower mean positive mood (b=-0.64, SE 0.28, P=.02) during study participation were found. Emotional flexibility was significantly enhanced in the TG. Additionally, dissatisfaction with social contacts was associated with both a decreased positive mood (b=-0.56, SE 0.15, P<.001) and an increased negative mood (b=0.45, SE 0.12, P<.001). CONCLUSIONS: This study showed several significant associations between mood and self-efficacy as well as those between mood and anxiety in students with elevated stress levels, for example, suggesting that improving mood in people with low mood could enhance the effects of digital self-efficacy training. In addition, engaging in 1-week self-efficacy training was associated with increased emotional flexibility. Future work is needed to replicate and investigate the training's effects in other groups and settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05617248; https://clinicaltrials.gov/study/NCT05617248.
BACKGROUND: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE: This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS: In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net-based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS: Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS: The Dynamic Modelling of Resilience-Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39817.
Background: Positive prospective mental imagery plays an important role in mental well-being, and depressive symptoms have been associated with difficulties in generating positive prospective mental images (PPMIs). We used a mobile app to gather PPMIs generated by young adults during the COVID-19 pandemic and analyzed content, characteristics, and associations with depressive symptoms. Methods: This is a secondary analysis of a randomized controlled trial with 95 healthy young adults allocated into two groups (intervention and control). Participants used the mobile app decreasing mental health symptoms for seven consecutive days. Fifty participants in the intervention group reported PPMIs at least three times per day using a mobile app inducing PPMI generation. We categorized entries into themes and applied moderation models to investigate associations between PPMI characteristics and depressive symptoms. Results: We distinguished 25 PPMI themes. The most frequent were related to consuming food and drinks, watching TV/streaming platforms, and doing sports. Vividness and ease of generation of PPMIs, but not their anticipation, pleasure intensity or number of engagements with the app were associated with fewer depressive symptoms. Conclusions: We identified PPMI themes in young adults and found significant negative associations between depressive symptoms and vividness and generation ease of PPMIs. These results may inform prevention and intervention science, including the design of personalized interventions. We discuss implications for future studies and treatment development for individuals experiencing diminished PPMI. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-023-10378-5.
Hemoglobin from either red meat or bowel bleeding may promote oxidative stress and increase the risk of colorectal cancer (CRC). Additionally, solid cancers or their metastases may be present with localized bruising. Escape from therapy-induced senescence (TIS) might be one of the mechanisms of tumor re-growth. Therefore, we sought to study whether hemin can cause escape from TIS in CRC. To induce senescence, human colon cancer cells were exposed to a chemotherapeutic agent irinotecan (IRINO). Cells treated with IRINO exhibited common hallmarks of TIS. To mimic bleeding, colon cancer cells were additionally treated with hemin. High hemin concentration activated heme oxygenase-1 (HO-1), induced escape from TIS and epithelial-to-mesenchymal transition, and augmented progeny production. The effect was even stronger in hypoxic conditions. Similar results were obtained when TIS cells were treated with another prooxidant agent, H2O2. Silencing of antioxidative enzymes such as catalase (CAT) or glutathione peroxidase-1 (GPx-1) maintained colon cancer cells in a senescent state. Our study demonstrates that a high hemin concentration combined with an increased activity of antioxidative enzymes, especially HO-1, leads to escape from the senescence of colon cancer cells. Therefore, our observations could be used in targeted anti-cancer therapy.
Ploidy increase has been shown to occur in different type of tumors and participate in tumor initiation and resistance to the treatment. Polyploid giant cancer cells (PGCCs) are cells with multiple nuclei or a single giant nucleus containing multiple complete sets of chromosomes. The mechanism leading to formation of PGCCs may depend on: endoreplication, mitotic slippage, cytokinesis failure, cell fusion or cell cannibalism. Polyploidy formation might be triggered in response to various genotoxic stresses including: chemotherapeutics, radiation, hypoxia, oxidative stress or environmental factors like: air pollution, UV light or hyperthermia. A fundamental feature of polyploid cancer cells is the generation of progeny during the reversal of the polyploid state (depolyploidization) that may show high aggressiveness resulting in the formation of resistant disease and tumor recurrence. Therefore, we propose that modern anti-cancer therapies should be designed taking under consideration polyploidization/ depolyploidization processes, which confer the polyploidization a hidden potential similar to a Trojan horse delayed aggressiveness. Various mechanisms and stress factors leading to polyploidy formation in cancer cells are discussed in this review.
Neoplasm Recurrence, Local , Polyploidy , Cell Nucleus , Giant Cells , Humans , Neoplasm Recurrence, Local/pathology
The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.
COVID-19/psychology , Mental Health , Resilience, Psychological , Social Factors , Stress, Psychological/prevention & control , Adult , COVID-19/prevention & control , Cross-Sectional Studies , Disease Transmission, Infectious/prevention & control , Europe , Female , Humans , Male , Middle Aged , Multivariate Analysis , Protective Factors , Regression Analysis , Social Support , Young Adult
BACKGROUND: A growing number of psychological interventions are delivered via smartphones with the aim of increasing the efficacy and effectiveness of these treatments and providing scalable access to interventions for improving mental health. Most of the scientifically tested apps are based on cognitive behavioral therapy (CBT) principles, which are considered the gold standard for the treatment of most mental health problems. OBJECTIVE: This review investigates standalone smartphone-based ecological momentary interventions (EMIs) built on principles derived from CBT that aim to improve mental health. METHODS: We searched the MEDLINE, PsycINFO, EMBASE, and PubMed databases for peer-reviewed studies published between January 1, 2007, and January 15, 2020. We included studies focusing on standalone app-based approaches to improve mental health and their feasibility, efficacy, or effectiveness. Both within- and between-group designs and studies with both healthy and clinical samples were included. Blended interventions, for example, app-based treatments in combination with psychotherapy, were not included. Selected studies were evaluated in terms of their design, that is, choice of the control condition, sample characteristics, EMI content, EMI delivery characteristics, feasibility, efficacy, and effectiveness. The latter was defined in terms of improvement in the primary outcomes used in the studies. RESULTS: A total of 26 studies were selected. The results show that EMIs based on CBT principles can be successfully delivered, significantly increase well-being among users, and reduce mental health symptoms. Standalone EMIs were rated as helpful (mean 70.8%, SD 15.3; n=4 studies) and satisfying for users (mean 72.6%, SD 17.2; n=7 studies). CONCLUSIONS: Study quality was heterogeneous, and feasibility was often not reported in the reviewed studies, thus limiting the conclusions that can be drawn from the existing data. Together, the studies show that EMIs may help increase mental health and thus support individuals in their daily lives. Such EMIs provide readily available, scalable, and evidence-based mental health support. These characteristics appear crucial in the context of a global crisis such as the COVID-19 pandemic but may also help reduce personal and economic costs of mental health impairment beyond this situation or in the context of potential future pandemics.
Cognitive Behavioral Therapy , Ecological Momentary Assessment , Mental Disorders/therapy , Mental Health , Mobile Applications , Smartphone , Telemedicine/methods , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2
Glioblastoma (GBM) is a malignant, primary brain tumor, highly resistant to conventional therapies. Temozolomide (TMZ) is a first line therapeutic agent in GBM patients, however, survival of such patients is poor. High level of DNA repair protein, O6-methylguanine-DNA-methyltransferase (MGMT) and occurrence of glioma stem-like cells contribute to GBM resistance to the drug. Here, we explored a possibility of epigenetic reprograming of glioma cells to increase sensitivity to TMZ and restore apoptosis competence. We combined TMZ treatment with BIX01294, an inhibitor of histone methyltransferase G9a, known to be involved in cancerogenesis. Two treatment combinations were tested: BIX01294 was administered to human LN18 and U251 glioma cell cultures 48 h before TMZ or 48 h after TMZ treatment. Despite their different status of the MGMT gene promoter, there was no correlation with the response to TMZ. The analyses of cell viability, appearance of apoptotic alterations in morphology of cells and nuclei, and markers of apoptosis, such as levels of cleaved caspase 3, caspase 7 and PARP, revealed that both pre-treatment and post-treatment with BIX01294 sensitize glioma cells to TMZ. The additive effect was stronger in LN18 cells. Moreover, BIX01294 enhanced the cytotoxic effect of TMZ on glioma stem-like cells, although it was not associated with modulation of the pluripotency markers (NANOG, SOX2, CD133) expression or methylation of NANOG and SOX2 gene promoters. Accordingly, knockdown of methyltransferase G9a augments TMZ-induced cell death in LN18 cells. We found the significant increases of the LC3-II levels in LN18 cells treated with BIX01294 alone and with drug combination that suggests involvement of autophagy in enhancement of anti-tumor effect of TMZ. Treatment with BIX01294 did not affect methylation of the MGMT gene promoter. Altogether, our results suggest that G9a is a potential therapeutic target in malignant glioma and the treatment with the G9a inhibitor reprograms glioma cells and glioma stem-like cells to increase sensitivity to TMZ and restore apoptosis competence.
BACKGROUND: The field of protein sequence analysis is dominated by tools rooted in substitution matrices and alignments. A complementary approach is provided by methods of quantitative characterization. A major advantage of the approach is that quantitative properties defines a multidimensional solution space, where sequences can be related to each other and differences can be meaningfully interpreted. RESULTS: Quantiprot is a software package in Python, which provides a simple and consistent interface to multiple methods for quantitative characterization of protein sequences. The package can be used to calculate dozens of characteristics directly from sequences or using physico-chemical properties of amino acids. Besides basic measures, Quantiprot performs quantitative analysis of recurrence and determinism in the sequence, calculates distribution of n-grams and computes the Zipf's law coefficient. CONCLUSIONS: We propose three main fields of application of the Quantiprot package. First, quantitative characteristics can be used in alignment-free similarity searches, and in clustering of large and/or divergent sequence sets. Second, a feature space defined by quantitative properties can be used in comparative studies of protein families and organisms. Third, the feature space can be used for evaluating generative models, where large number of sequences generated by the model can be compared to actually observed sequences.
Sequence Analysis, Protein/methods , Software , Amino Acids/chemistry , Cluster Analysis , Humans , Proteins/chemistry , Proteins/classification
We present a case report of potential reduction of hospitalization costs due to utilization of PET/CT in a diagnostic work-up of a patient with an implantable cardioverter-defibrillator and suspicion of infective endocarditis. The PET/CT scan would have shorten hospital stay, prevented clinical complications and reduced the cost of hospitalization by 45%.
Defibrillators, Implantable/adverse effects , Endocarditis/diagnosis , Length of Stay/economics , Positron-Emission Tomography/economics , Tomography, X-Ray Computed/economics , Aged , Cost Savings , Defibrillators, Implantable/economics , Endocarditis/etiology , Humans , Male
