Citations

Abstract Introduction: There is insufficient knowledge about the feasibility and effect of mind-body intervention on QOL and stress at initial diagnosis and shortly after undergoing breast cancer surgical treatment. The pre-operative and post-operative period can be stressful, distressing and anxiety provoking for many women. Mind-body interventions such as meditation, relaxation and mindfulness can offset distress and is an option to cope with the stresses of treatment. We investigated the role of wearable mindfulness based technology in patients newly diagnosed breast cancer patients. Methods: This randomized study compared the Muse EEG mindfulness sensing headset device (n=16) to a stress reduction education control group (n=13). Primary outcomes included quality of life (QOL), stress, and fatigue via validated, standardized scales/subscales: Functional Assessment of Cancer Therapies – General (FACT-G), Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SI), and the Perceived Stress Scale (PSS). Participants from an academic cancer center were randomized to the wearable device or stress education material prior to surgery. Participants completed questionnaires at initial diagnosis and at specific time points during the breast cancer surgical journey: pre-surgery, post-surgery (2 weeks), and at 3 months. Usage was directly from Muse and via written log. Was It Worth It (WIWI) survey was conducted at 3 months. Results: Mindfulness via the headset devise was feasible and worthwhile (71.4% intervention group). The scales of QOL, fatigue, and stress improved in both groups at 3 months compared to baseline (MFSI-E, MFSI-M, MFSI-V, FACT-EWB, and PSS). Participants randomized to the mindfulness headset device had improved fatigue and QOL at 2 weeks post-operatively (MFSI-E, MFSI-V, MFSI-T, FACT-PWB, FACT-EWB) and in total MFSI at 3 months. The results were not significantly different between groups. High mindfulness headset utilizers (>30 sessions) compared to below average utilizers differed at the 3 month visit in fatigue and QOL (MFSI-G, MFSI-P, FACT-PWB, and FACT-Total). Conclusion: Our study demonstrated that the use of wearable mindfulness sensing headset device was feasible, simple to use, low cost, and integrated into the surgical breast cancer journey. Overall, among breast cancer patients undergoing surgery there was improvement in QOL, fatigue, and stress with mind-body interventions around surgery compared to baseline. Participants randomized to the wearable mindfulness headset device trended toward outcomes sooner (2 week follow-up) and with high utilization. Further research is needed to determine significance of these outcomes and long term impact in care of cancer survivors. Citation Format: Pruthi S, Millstine DM, Bhagra A, Nguyen M-D. Effect of wearable wellness brain sensing mindfulness-based technology in newly diagnosed surgical breast cancer patients: A randomized intervention [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-12.

Abstract Motivation Both single-cell RNA sequencing (scRNA-seq) and DNA sequencing (scDNA-seq) have been applied for cell-level genomic profiling. For mutation profiling, the latter seems more natural. However, the task is highly challenging due to the limited input materials from only two copies of DNA molecules, while whole-genome amplification generates biases and other technical noises. ScRNA-seq starts with a higher input amount, so generally has better data quality. There exists various methods for mutation detection from DNA sequencing, it is not clear whether these methods work for scRNA-seq data. Results Mutation detection methods developed for either bulk-cell sequencing data or scDNA-seq data do not work well for the scRNA-seq data, as they produce substantial numbers of false positives. We develop a novel and robust statistical method—called SCmut—to identify specific cells that harbor mutations discovered in bulk-cell data. Statistically SCmut controls the false positives using the 2D local false discovery rate method. We apply SCmut to several scRNA-seq datasets. In scRNA-seq breast cancer datasets SCmut identifies a number of highly confident cell-level mutations that are recurrent in many cells and consistent in different samples. In a scRNA-seq glioblastoma dataset, we discover a recurrent cell-level mutation in the PDGFRA gene that is highly correlated with a well-known in-frame deletion in the gene. To conclude, this study contributes a novel method to discover cell-level mutation information from scRNA-seq that can facilitate investigation of cell-to-cell heterogeneity. Availability and implementation The source codes and bioinformatics pipeline of SCmut are available at https://github.com/nghiavtr/SCmut. Supplementary information Supplementary data are available at Bioinformatics online.

Abstract Tumor–stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions are partly comprised of the cross-talk between tumor and stromal fibroblasts, but the key molecular mechanisms within the cross-talk that govern cancer invasion are still unclear. Here, we adapted our previously developed microfluidic device as a 3D in vitro organotypic model to mechanistically study tumor–stroma interactions by mimicking the spatial organization of the tumor microenvironment on a chip. We cocultured breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions, respectively, and combined functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor–stroma cross-talk on invasion. This led to the observation that cancer-associated fibroblasts (CAF) enhanced invasion in 3D by inducing expression of a novel gene of interest, glycoprotein nonmetastatic B (GPNMB), in breast cancer cells, resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAF on enhanced cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient-specific tumor microenvironments to investigate the cellular and molecular consequences of tumor–stroma interactions. Significance: An organotypic model of tumor–stroma interactions on a microfluidic chip reveals that CAFs promote invasion by enhancing expression of GPNMB in breast cancer cells.

Patients with Crohn’s disease commonly develop ileal and less commonly colonic strictures, containing various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment, predominantly fibrotic strictures currently require endoscopic balloon dilation or surgery. Therefore, differentiation of the main components of a stricturing lesion is key for defining the therapeutic management. The role of endoscopy to diagnose the nature of strictures is limited by the superficial inspection of the intestinal mucosa, the lack of depth of mucosal biopsies and by the risk of sampling error due to a heterogeneous distribution of inflammation and fibrosis within a stricturing lesion. These limitations may be in part overcome by cross-sectional imaging techniques such as ultrasound, CT and MRI, allowing for a full thickness evaluation of the bowel wall and associated abnormalities. This systematic literature review provides a comprehensive summary of currently used radiologic definitions of strictures. It discusses, by assessing only manuscripts with histopathology as a gold standard, the accuracy for diagnosis of the respective modalities as well as their capability to characterise strictures in terms of inflammation and fibrosis. Definitions for strictures on cross-sectional imaging are heterogeneous; however, accuracy for stricture diagnosis is very high. Although conventional cross-sectional imaging techniques have been reported to distinguish inflammation from fibrosis and grade their severity, they are not sufficiently accurate for use in routine clinical practice. Finally, we present recent consensus recommendations and highlight experimental techniques that may overcome the limitations of current technologies.