Start With the Body or the Mind? Differential Benefits of Mindfulness and Qigong Practices for Colorectal Cancer Survivors: A Qualitative Study.

BACKGROUND: Mindfulness and qigong are 2 distinct forms of mind-body practice that have been well-received by cancer survivors. Although there is evidence supporting the effectiveness of mindfulness or qigong in promoting wellness of cancer survivors, little is known about the differential benefits of these common forms of mind-body practices among survivors. OBJECTIVE: To compare the potential biopsychosocial-spiritual impacts of mindfulness and Baduanjin (BDJ) qigong on colorectal cancer survivors. METHODS: Sixty cancer survivors who participated in a mindfulness intervention (n = 38) and BDJ qigong (n = 22) intervention were invited to provide qualitative feedback for their experiences. Content analyses were conducted to identify emerging themes from the data, and χ2 tests were conducted to compare the responses of the mindfulness and BDJ groups in the major categories. RESULTS: Both practices positively influenced psychosocial wellness. The practice of BDJ qigong led to more prominent improvements in physical well-being, whereas mindfulness worked best in enhancing spiritual growth and intrapersonal connectedness. CONCLUSIONS: Survivors of colorectal cancer who are looking for ways to enhance their vitality and rejuvenate their physical body may find the practice of BDJ helpful, whereas survivors who are looking for spiritual comfort or growth may consider practicing mindfulness as an entry point toward mind-body unity. IMPLICATIONS FOR PRACTICE: Mindfulness and BDJ may be helpful for survivors of colorectal cancer to improve their holistic wellness. Oncology nurses can consider prescription of mindfulness and/or BDJ for patients recovering from colorectal cancer.

Protocol for a mixed-methods randomised controlled trial evaluating the effectiveness of a dyadic expressive arts-based intervention in improving the psychosocial well-being of children with intellectual disability in special schools and their mothers.

INTRODUCTION: Mothers of children with intellectual disability (ID) are often distressed because of intensive workloads and difficulties in communicating with their children. Given the interdependence between the psychosocial well-being of such dyads, interventions that promote parent-child relationships and mutual communication would be beneficial. Arts provide alternative avenues for expression and offer an imaginative and playful environment for discovering new communication strategies. Given the lack of studies on arts-based dyadic interventions, this study aims to examine the effectiveness of dyadic expressive arts-based intervention (EXAT) in improving the psychosocial outcomes of children with ID and their mothers and the mother-child relationships. METHODS AND ANALYSIS: This study will adopt a mixed-methods randomised controlled trial design, wherein 154 dyads of children with ID and their mothers will be randomised into either the dyadic EXAT group or the treatment-as-usual waitlist control group. Quantitative data will be collected at four time points: baseline (T0), postintervention (T1), 3-month postintervention (T2) and 6-month postintervention (T3). Qualitative data will be collected from a subset of 30 mothers in the intervention group at T1 and T3 to document their experiences and perceived changes after the intervention. Mixed-effects models and path analysis will be adopted to analyse the quantitative data, whereas thematic analysis will be applied to the qualitative data. Both sets of data will be triangulated for an integrated view of the effectiveness and mechanism of the intervention. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Research Ethics Committee of the University of Hong Kong (Ref. no.: EA200329). Written consent forms will be obtained from all recruited participants (mothers, children with ID and teachers/social workers) before data collection. The study findings will be disseminated in international conferences and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: NCT05214859.

Comparison of passive drool and cotton-based collection methods for salivary C-reactive protein measurement.

Saliva collection and handling procedures for salivary C-reactive protein (CRP) can be challenging due to a lack of standardized protocols. This study compared two collection methods used to quantify salivary CRP. Twenty-two Chinese adults provided two unstimulated whole saliva samples using passive drool and cotton-based collection devices in two consecutive mornings at baseline and 1 month later. The effects of various factors on CRP levels were analyzed using linear mixed models. Salivary CRP levels were significantly affected by collection time and method, but not day or wave. The CRP peaked upon awakening and declined 45 min later. CRP levels were significantly higher in the passive drool than in the cotton-based method. The Bland-Altman plot revealed relative and proportional biases. The difference in the CRP levels between the methods decreased as the CRP levels increased. Results suggest that passive drool and cotton-based collection methods should not be used interchangeably for measuring low levels of salivary CRP.

Psychometric properties of the Chinese version of Five Facet Mindfulness Questionnaire-short form in cancer patients: a Bayesian structural equation modeling approach.

BACKGROUND: Mindfulness has emerged as an important correlate of well-being in various clinical populations. The present study evaluated the psychometric properties of the 20-item short form of the Five Facet Mindfulness Questionnaire (FFMQ-SF) in the Chinese context. METHODS: The study sample was 127 Chinese colorectal cancer patients who completed the FFMQ-SF and validated physical and mental health measures. Factorial validity of the FFMQ-SF was assessed using Bayesian structural equation modeling (BSEM) via informative priors on cross-loadings and residual covariances. Linear regression analysis examined its convergent validity with the health measures on imputed datasets. RESULTS: The five-factor BSEM model with approximate zero cross-loadings and one residual covariance provided an adequate model fit (PPP = 0.07, RMSEA = 0.06, CFI = 0.95). Satisfactory reliability (ω = 0.77-0.85) was found in four of the five facets (except nonjudging). Acting with awareness predicted lower levels of perceived stress, negative affect, anxiety, depression, and illness symptoms (ß = - 0.37 to - 0.42) and better quality of life (ß = 0.29-0.32). Observing, nonjudging, and nonreacting did not show any significant associations (p > .05) with health measures. Acting with awareness was not significantly correlated (r < 0.15) with the other four facets. CONCLUSION: The present findings provide partial support for the psychometric properties of the FFMQ-SF in colorectal cancer patients. The nonjudging facet showed questionable validity and reliability in the present sample. Further studies with larger sample sizes are needed to elucidate the viability of FFMQ-SF as a measure of mindfulness facets in cancer patients.

A randomised controlled trial of expressive arts-based intervention for young stroke survivors.

BACKGROUND: Stroke causes lasting brain damage that has numerous impacts on the survivor's physical, psychosocial, and spiritual well-being. Young survivors (< 65 years old) tend to suffer more because of their longer overall survival time. Expressive arts-based intervention is considered a holistic approach for stroke rehabilitation because it allows participants to express their thoughts and emotions through the arts. The group environment also promotes mutual support among participants. The creative art-making process helps expand participants' creativity and imagination as well as promote a sense of aesthetic appreciation. Previous studies have shown the effectiveness of the arts-based intervention in managing stroke and its psychosocial-spiritual comorbidities. Nevertheless, a systematic study has not been conducted, including in young survivors. This trial plans to investigate the effectiveness of an expressive arts-based intervention on bio-psychosocial-spiritual outcomes in young Chinese stroke survivors. METHODS/DESIGN: A single-blind, two-arm cluster randomised control trial with a waitlist control design will be adopted. One hundred and fifty-four stroke survivors, aged 18-64 years with modified Rankin Scale scores of 1-4, will be screened and randomised to either an expressive arts-based intervention group or a treatment-as-usual waitlist control group. The intervention group will receive a 90-min session once a week for a total of 8 weeks. All participants will be assessed three times: at baseline, 8 weeks, and 8 months after the baseline. Study outcomes include measures of depression and anxiety, perceived stress, perceived social support, hope, spiritual well-being, quality of life, salivary cortisol, blood pressure, and heart rate. DISCUSSION: This study is expected to contribute to the current knowledge on the effectiveness of an arts-based intervention on the holistic wellness of young stroke survivors. The findings will help stroke survivors and healthcare professionals make better choices in selecting practices that will yield maximum benefits, satisfaction, adherence, and sustainability. In addition, the examination of the relationships between bio-psychosocial-spiritual variables will help contribute to the development of holistic care for the survivors. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03729648 . Registered 31 October 2018 - Retrospectively registered, (329 words).

Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumors.

Subsets of breast tumors present major clinical challenges, including triple-negative, metastatic/recurrent disease and rare histologies. Here, we developed 37 patient-derived xenografts (PDX) from these difficult-to-treat cancers to interrogate their molecular composition and functional biology. Whole-genome and transcriptome sequencing and reverse-phase protein arrays revealed that PDXs conserve the molecular landscape of their corresponding patient tumors. Metastatic potential varied between PDXs, where low-penetrance lung micrometastases were most common, though a subset of models displayed high rates of dissemination in organotropic or diffuse patterns consistent with what was observed clinically. Chemosensitivity profiling was performed in vivo with standard-of-care agents, where multi-drug chemoresistance was retained upon xenotransplantation. Consolidating chemogenomic data identified actionable features in the majority of PDXs, and marked regressions were observed in a subset that was evaluated in vivo. Together, this clinically-annotated PDX library with comprehensive molecular and phenotypic profiling serves as a resource for preclinical studies on difficult-to-treat breast tumors.

Stress and psychosomatic symptoms in Chinese adults with sleep complaints: mediation effect of self-compassion.

Although stress has been widely acknowledged to link to psychosomatic dysfunctioning, the underlying mechanism that transmits the impact is not adequately investigated. This study examined self-compassion as a potential mediator that may explain the pathway from stress to depressive and somatic symptoms. Data in the present study were drawn from a baseline survey of 998 Chinese participants who enrolled in an intervention study on sleep disturbance in Hong Kong. Participants completed measures of perceived stress, self-compassion, depressive symptoms, and somatic symptoms. The results showed that stress was associated with depressive symptoms (r = .79, p < .01) and somatic symptoms (r = .47, p < .01). The path analyses showed that low levels of self-compassion mediated the association between stress and psychosomatic symptoms. Our findings provide insight into the pathway how stress affects psychosomatic symptoms. The intervention programs for stress management to improve psychological and physical functioning are recommended to consider self-compassion as a promising component in practice.

Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispersion.

Engineered in-vitro cell line mixtures and robust evaluation of computational methods for clonal decomposition and longitudinal dynamics in cancer.

Characterization and quantification of tumour clonal populations over time via longitudinal sampling are essential components in understanding and predicting the response to therapeutic interventions. Computational methods for inferring tumour clonal composition from deep-targeted sequencing data are ubiquitous, however due to the lack of a ground truth biological data, evaluating their performance is difficult. In this work, we generate a benchmark data set that simulates tumour longitudinal growth and heterogeneity by in vitro mixing of cancer cell lines with known proportions. We apply four different algorithms to our ground truth data set and assess their performance in inferring clonal composition using different metrics. We also analyse the performance of these algorithms on breast tumour xenograft samples. We conclude that methods that can simultaneously analyse multiple samples while accounting for copy number alterations as a factor in allelic measurements exhibit the most accurate predictions. These results will inform future functional genomics oriented studies of model systems where time series measurements in the context of therapeutic interventions are becoming increasingly common. These studies will need computational models which accurately reflect the multi-factorial nature of allele measurement in cancer including, as we show here, segmental aneuploidies.

Study protocol on comparative effectiveness of mindfulness meditation and qigong on psychophysiological outcomes for patients with colorectal cancer: a randomized controlled trial.

BACKGROUND: Colorectal cancer imposes threats to patients' well-being. Although most physical symptoms can be managed by medication, psychosocial stressors may complicate survival and hamper quality of life. Mindfulness and Qigong, two kinds of mind-body exercise rooted in Eastern health philosophy, has been found effective in symptoms management, improving mental health, and reducing stress. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the comparative effectiveness of mindfulness and Baduanjin intervention on the bio-psychosocial wellbeing of people with colorectal cancer. METHODS/ DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred eighty-nine participants will be randomized into (i) Mindfulness, (ii) Baduanjin, or (iii) waitlist control groups. Participants in both the Baduanjin and mindfulness groups will receive 8-weeks of specific intervention. All three groups will undergo four assessment phases: (i) at baseline, (ii) at 4-week, (iii) at 8-week (post-intervention), and 6-month post-intervention (maintenance). All participants will be assessed in terms of cancer-related symptoms and symptom distress, mental health status, quality of life, stress level based on physiological marker. DISCUSSION: Based on prior research studies, participants in both the mindfulness and Baduanjn intervention group are expected to have better symptoms management, lower stress level, better mental health, and higher level of quality of life than the control group. This study contributes to better understanding on the common and unique effectiveness of mindfulness and Baduanjin qigong, as such patients and qualified healthcare professionals can select or provide practices which will produce maximum benefits, satisfaction, adherence, and sustainability. TRIAL REGISTRATION: The trial has been registered in the Clinical Trials Centre of the University of Hong Kong ( HKCTR-2198 ) on 08 March 2017.

Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes.

We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.

CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.

CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, we explore the connectivity of genomic CDC-like kinase splicing functions by applying graduated, short-exposure, pharmacological CDC-like kinase inhibition using a novel small molecule (T3) with very high potency, selectivity, and cell-based stability. Using RNA-Seq, we define CDC-like kinase-responsive alternative splicing events, the large majority of which monotonically increase or decrease with increasing CDC-like kinase inhibition. We show that distinct RNA-binding motifs are associated with T3 response in skipped exons. Unexpectedly, we observe dose-dependent conjoined gene transcription, which is associated with motif enrichment in the last and second exons of upstream and downstream partners, respectively. siRNA knockdown of CLK2-associated genes significantly increases conjoined gene formation. Collectively, our results reveal an unexpected role for CDC-like kinase in conjoined gene formation, via regulation of 3'-end processing and associated splicing factors.The phosphorylation of serine/arginine-rich proteins by CDC-like kinase is a central regulatory mechanism for RNA splicing reactions. Here, the authors synthesize a novel small molecule CLK inhibitor and map CLK-responsive alternative splicing events and discover an effect on conjoined gene transcription.

Psychiatric symptoms mediate the effects of neurological soft signs on functional outcomes in patients with chronic schizophrenia: A longitudinal path-analytic study.

Neurological soft signs (NSS) in motor coordination and sequencing occur in schizophrenia patients and are an intrinsic sign of the underlying neural dysfunctions. The present longitudinal study explored the relationships among NSS, psychiatric symptoms, and functional outcomes in 151 Chinese patients with chronic schizophrenia across a 6-month period. The participants completed neurological assessments at baseline (Time 1), psychiatric interviews at Time 1 and 3-month follow-up (Time 2), and self-report measures on daily functioning at 6-month follow-up (Time 3). Two possible (combined and cascading) path models were examined on predicting the functional outcomes. Direct and indirect effects of Time 1 NSS on Time 3 functional outcomes via Time 2 psychiatric symptoms were evaluated using path analysis under bootstrapping. Motor coordination and sequencing NSS did not have significant direct effects on functional outcomes. Motor coordination NSS exerted significant and negative indirect effects on functional outcomes via psychiatric symptoms. These results contribute to a better understanding of the determinants of functional outcomes by showing significant indirect pathways from motor coordination NSS to functional outcomes via psychiatric symptoms. That motor sequencing NSS did not affect functional outcomes either directly or indirectly may be explained by their trait marking features.

Toward a Holistic Approach to Spiritual Health Care for People With Schizophrenia.

Medical and behavioral treatments are the predominant types of rehabilitation services for people with schizophrenia. Spirituality in people with schizophrenia remains poorly conceptualized, thereby limiting knowledge advancement in the area of spiritual health care services. To provide a framework for better clinical and research practices, we advocate a holistic approach to investigating spirituality and its application in spiritual health care services of people with schizophrenia.

Bimolecular complementation affinity purification (BiCAP) reveals dimer-specific protein interactions for ERBB2 dimers.

The dynamic assembly of multiprotein complexes is a central mechanism of many cell signaling pathways. This process is key to maintaining the spatiotemporal specificity required for an accurate, yet adaptive, response to rapidly changing cellular conditions. We describe a technique for the specific isolation and downstream proteomic characterization of any two interacting proteins, to the exclusion of their individual moieties and competing binding partners. We termed the approach bimolecular complementation affinity purification (BiCAP) because it combines the use of conformation-specific nanobodies with a protein-fragment complementation assay with affinity purification. Using BiCAP, we characterized the specific interactome of the epidermal growth factor receptor (EGFR) family member ERBB2 when in the form of a homodimer or when in the form of a heterodimer with either EGFR or ERBB3. We identified dimer-specific interaction patterns for key adaptor proteins and identified a number of previously unknown interacting partners. Functional analysis for one of these newly identified partners revealed a noncanonical mechanism of extracellular signal-regulated kinase (ERK) activation that is specific to the ERBB2:ERBB3 heterodimer and acts through the adaptor protein FAM59A in breast cancer cells.

Associations between diurnal cortisol patterns and lifestyle factors, psychotic symptoms, and neurological deficits: A longitudinal study on patients with chronic schizophrenia.

The present study examined the relationships between diurnal cortisol patterns and perceived stress, lifestyle factors, psychotic symptoms, neurological deficits, and daily functioning in patients with chronic schizophrenia. The participants were 149 Chinese patients with chronic schizophrenia, who provided salivary cortisol measures upon waking, before lunchtime, and before bedtime at baseline (Time 1). Self-report measures on perceived stress and lifestyle factors such as body-mass index and daily exercise span were recorded at Time 1. Diagnostic assessments on psychotic symptoms, neurological deficits, and daily functioning were made at Time 1 and Time 2 (3 months later). Latent growth modeling and path modeling analysis were performed to investigate the diurnal cortisol patterns and the relationships with the study variables, respectively. Greater perceived stress and body-mass index and less physical activity were significantly linked to reduced cortisol decline. Reduced cortisol decline at Time 1 significantly predicted greater psychotic (positive and negative) symptoms and more severe neurological deficits in motor coordination and sequencing of complex motor acts at Time 2. The present results contribute to a better understanding of the diurnal cortisol patterns among chronic schizophrenia patients and the associations with lifestyle factors, psychotic symptoms, and neurological deficits. The findings lend support to the neural diathesis-stress model and suggest that hypothalamic-pituitary-adrenal axis may potentially mediate the effects of lifestyle factors on psychotic symptoms and neurological deficits.

Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers.

Clonal genotype and population structure inference from single-cell tumor sequencing.

Single-cell DNA sequencing has great potential to reveal the clonal genotypes and population structure of human cancers. However, single-cell data suffer from missing values and biased allelic counts as well as false genotype measurements owing to the sequencing of multiple cells. We describe the Single Cell Genotyper (https://bitbucket.org/aroth85/scg), an open-source software based on a statistical model coupled with a mean-field variational inference method, which can be used to address these problems and robustly infer clonal genotypes.

A randomized controlled trial on the psychophysiological effects of physical exercise and Tai-chi in patients with chronic schizophrenia.

The chronic and prevalent natures of schizophrenia result in long-term institutionalization for the patients. Conventional treatment of anti-psychotic medication on management of psychotic symptoms often brings on severe side effects and reduces patients' well-being. Tai-chi is a mind-body exercise that underscores motor coordination and relaxation. This 3-arm randomized controlled trial investigated the psychophysiological benefits of Tai-chi on 153 chronic schizophrenia patients, who were recruited from a mental health rehab complex and randomized into Tai-chi, exercise, or waitlist control groups. Both intervention groups received 12weeks of specific intervention plus standard medication received by the controls. All participants completed psychiatric interviews, self-report questionnaires, performance tasks, and salivary cortisol measures at baseline, 3-month, and 6-month follow-up on psychotic symptoms, motor coordination, memory, daily living function, and stress. Multigroup latent growth modeling was used to evaluate the intervention effects on the outcomes. Compared to controls, the Tai-chi group showed significant decreases in motor deficits and increases in backward digit span and mean cortisol, while the exercise group displayed significant decreases in motor deficits, negative and depression symptoms and increases in forward digit span, daily living function, and mean cortisol. The two interventions did not show significantly different therapeutic effects, except for fewer symptom manifestations in the exercise group. These results suggest psychophysiological benefits for Tai-chi on chronic schizophrenia patients in terms of motor coordination and memory. Though both Tai-chi and exercise groups tended to manifest fewer symptoms than the control group, the exercise group showed better symptoms management than the Tai-chi group.

Psychometric validation of the consensus five-factor model of the Positive and Negative Syndrome Scale.

BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is widely used for clinical assessment of symptoms in schizophrenia. Instead of the traditional pyramidal model, recent literature supports the pentagonal model for the dimensionality of the PANSS. AIM: The present study aimed to validate the consensus five-factor model of the PANSS and evaluate its convergent validity. METHODS: Participants were 146 Chinese chronic schizophrenic patients who completed diagnostic interviews and cognitive assessments. Exploratory structural equation modeling (ESEM) was performed to investigate the dimensionality of the PANSS. Covariates (age, sex, and education level) and concurrent outcomes (perceived stress, memory, daily living functions, and motor deficits) were added in the ESEM model. RESULTS: The results supported the consensus 5-factor underlying structure, which comprised 20 items categorized into positive, negative, excitement, depression, and cognitive factors with acceptable reliability (α=.69-.85) and strong factor loadings (λ=.41-.93). The five factors, especially the cognitive factor, showed evident convergent validity with the covariates and concurrent outcomes. CONCLUSION: The results support the consensus five-factor structure of the PANSS as a robust measure of symptoms in schizophrenia. Future studies could explore the clinical and practical utility of the consensus five-factor model.