scPipe: an extended preprocessing pipeline for comprehensive single-cell ATAC-Seq data integration in R/Bioconductor.

scPipe is a flexible R/Bioconductor package originally developed to analyse platform-independent single-cell RNA-Seq data. To expand its preprocessing capability to accommodate new single-cell technologies, we further developed scPipe to handle single-cell ATAC-Seq and multi-modal (RNA-Seq and ATAC-Seq) data. After executing multiple data cleaning steps to remove duplicated reads, low abundance features and cells of poor quality, a SingleCellExperiment object is created that contains a sparse count matrix with features of interest in the rows and cells in the columns. Quality control information (e.g. counts per cell, features per cell, total number of fragments, fraction of fragments per peak) and any relevant feature annotations are stored as metadata. We demonstrate that scPipe can efficiently identify 'true' cells and provides flexibility for the user to fine-tune the quality control thresholds using various feature and cell-based metrics collected during data preprocessing. Researchers can then take advantage of various downstream single-cell tools available in Bioconductor for further analysis of scATAC-Seq data such as dimensionality reduction, clustering, motif enrichment, differential accessibility and cis-regulatory network analysis. The scPipe package enables a complete beginning-to-end pipeline for single-cell ATAC-Seq and RNA-Seq data analysis in R.

Benchmarking long-read RNA-sequencing analysis tools using in silico mixtures.

The lack of benchmark data sets with inbuilt ground-truth makes it challenging to compare the performance of existing long-read isoform detection and differential expression analysis workflows. Here, we present a benchmark experiment using two human lung adenocarcinoma cell lines that were each profiled in triplicate together with synthetic, spliced, spike-in RNAs (sequins). Samples were deeply sequenced on both Illumina short-read and Oxford Nanopore Technologies long-read platforms. Alongside the ground-truth available via the sequins, we created in silico mixture samples to allow performance assessment in the absence of true positives or true negatives. Our results show that StringTie2 and bambu outperformed other tools from the six isoform detection tools tested, DESeq2, edgeR and limma-voom were best among the five differential transcript expression tools tested and there was no clear front-runner for performing differential transcript usage analysis between the five tools compared, which suggests further methods development is needed for this application.

Strategies in activating lymphatic system on symptom distress and health-related quality of life in patients with heart failure: secondary analysis of a pilot randomized controlled trial.

Background: Abnormal interstitial fluid accumulation remains the major cause for patients with heart failure (HF) to endure a myriad of distressing symptoms and a decline in their health-related quality of life (HRQoL). The lymphatic system is essential in regulating fluid balance within the interstitial compartment and has recently been recognized as an important target for the prevention and mitigation of congestion. This study aimed to investigate the effects of exercises in activating lymphatic system on symptom distress and HRQoL among patients with HF. Methods and results: This was a pre-determined, secondary analysis of the TOLF-HF [The-Optimal-Lymph-Flow for Heart Failure (TOLF-HF)] study, a two-arm pilot randomized controlled trial evaluating the preliminary effects of the lymphatic exercise intervention in enhancing interstitial decongestion among patients with HF. Participants were randomized to receive either a four-week TOLF-HF program in addition to standard care or standard care alone. The Chinese version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) was employed to measure symptom distress and HRQoL before and after the intervention. Data analyses included descriptive statistics, the independent sample t-test, Pearson's chi-square test, the Mann-Whitney U test, and covariance analysis. Of the 66 patients enrolled, 60 completed the study. The study results exhibited that the TOLF-HF intervention were effective in alleviating both physical and psychological symptom distress. The intervention group yielded significantly lower MLHFQ total scores in comparison to the control group. The odd ratio of achieving meaningful improvement in HRQoL in TOLF-HF group was 2.157 times higher than those in the control group. Conclusions: The TOLF-HF program focusing on activating lymphatic system was effective in alleviating physical and psychological symptom distress as well as improving HRQoL for patients with HF. The tolerability, feasibility, and effectiveness of the TOLF-HF intervention make it a promising intervention for patients to manage HF. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier (ChiCTR2000039121).

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification.

The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

The Contribution of Cancer-Specific Psychosocial Factors to the Pain Experience in Cancer Survivors.

Palliative care teams are increasingly called up to manage chronic pain in cancer survivors. Chronic pain is common in cancer survivors and is heavily influenced by biopsychosocial factors. This study aimed to determine the relative contribution of unique cancer-specific psychosocial factors, pain catastrophizing, and multisite pain to the pain experience in 41 cancer survivors who completed curative cancer treatment. To test the research hypotheses, a series of nested linear regression models were used with likelihood ratio testing to test the individual and collective contribution of cancer-specific psychosocial factors (fear of cancer recurrence, cancer distress, cancer-related trauma), pain catastrophizing, and the number of pain sites on the pain experience. The results indicate pain catastrophizing and multisite pain explained a significant degree of variance in pain interference scores ( P < .001) and pain severity ( P = .005). Cancer-specific psychosocial factors did not significantly predict variability in pain interference ( P = .313) or pain severity ( P = .668) over and above pain catastrophizing and the number of sites of pain. In summary, pain catastrophizing and multisite pain contribute to the chronic cancer-related pain experienced by cancer survivors. Palliative care nurses are well positioned to improve chronic pain among cancer survivors by assessing and treating pain catastrophizing and multisite pain.

Sociodemographic characteristics, lifestyle behaviors, and symptoms associated with fluid overload among non-hospitalized and community-dwelling older adults with heart failure: A population-based approach.

BACKGROUND: Fluid overload is a major complication in patients with heart failure (HF) and the main reason for hospitalization. The purpose of the study was to explore the associations of fluid overload with sociodemographic characteristics, lifestyle behaviors, and symptoms among non-hospitalized and community-dwelling older adults with HF using large population data. METHODS: Descriptive and multivariate analyses were conducted on the Health and Retirement Study 2016. RESULTS: Fluid overload was prevalent in almost half of the sample. Female older adults with HF were more likely to have fluid overload (OR:1.43, p = 0.037) as well as being Black (OR:1.40, p = 0.041). Higher physical activity scores were associated with less likelihood of having fluid overload (OR:0.99, p = 0.025). Symptoms of shortness of breath (OR=2.18, p = 0.001), pain (OR=1.82, p < 0.001), and fatigue (OR=1.45, p = 0.025) were significantly associated with fluid overload. CONCLUSION: Female and Black community-dwelling older adults with HF are at higher risk of fluid overload. Symptoms of shortness of breath, pain, and fatigue are significant manifestations of fluid overload. Effective patient-centered interventions to promote fluid flow via physical activity may help older adults with HF manage fluid overload and alleviate associated symptoms.

[Inducible co-stimulatory molecules participate in mesenteric vascular endothelial-mesenchymal transition and sclerosis of mesenteric vessels in spontaneously hypertensive rats].

OBJECTIVE: To investigate the correlation of inducible co-stimulatory molecules (ICOS) with mesenteric vascular endothelial- mesenchymal transition (EndMT) and sclerosis in spontaneously hypertensive rats (SHR). METHODS: Twenty 4-week-old WKY rats and 20 SHRs of the same strain were both randomly divided into 4 groups for observation at 4, 6, 10 and 30 weeks of age. ICOS expression frequency in rat spleen CD4+T cells was analyzed using flow cytometry, and the expressions of ICOS, VE-cad, α-SMA and Col3 mRNA in rat mesentery were detected by RT-PCR. The distributions of ICOS, IL-17A and TGF-ß in rat mesentery were detected by immunohistochemistry. The levels of IL-17A and TGF-ß in rat plasma were measured using ELISA. The morphological changes of rat mesenteric vessels were observed with Masson staining. Spearman or Pearson correlation analyses were used to evaluate the correlation between ICOS expression and the expressions of the markers of vascular EndMT and sclerosis. RESULTS: Compared with the control WKY rats, the SHRs began to show significantly increased systolic blood pressure and ICOS expression frequency on CD4+T cells at 6 weeks of age (P < 0.05). In the SHRs, the mRNA and protein expressions of ICOS, α-SMA, Col3, IL-17A and TGF-ß in the mesentery were significantly higher than those in control group (P < 0.05), while the mRNA and protein expressions of VE-cad started to reduce significantly at 10 weeks of age (P < 0.05). The plasma levels of IL-17A and TGF-ß were significantly increased in SHRs since 6 weeks of age (P < 0.05) with progressive worsening of mesenteric vascular sclerosis (P < 0.05). ICOS mRNA and protein expression levels in the mesenteric tissues of SHRs began to show positive correlations with α-SMA and Col3 expression levels and the severity of vascular sclerosis at 6 weeks of age (P < 0.05) and a negative correlation with VE-cad expression level at 10 weeks (P < 0.05). CONCLUSION: ICOS play an important pathogenic role in EndMT and sclerosis of mesenteric vessels in essential hypertension by mediating related immune responses.

"It Is So Easy For Them to Dismiss": A Phenomenological Study of Cancer Survivors With Chronic Cancer-Related Pain.

Background: For many cancer survivors post-cure, chronic pain is a devastating complication of cancer treatment. The prevalence of chronic pain among cancer survivors is double that of the general population. However, little is known about the pain experience of cancer survivors who may have a different perspective than people with advanced cancer or people with noncancer pain. Objective: To understand the lived experience of chronic cancer-related pain in cancer survivors. Methods: We used a qualitative design with a descriptive phenomenological method to conduct in-depth interviews of 13 cancer survivors residing in the United States who completed curative cancer therapy, were at least three months from treatment, and experienced pain attributable to cancer. Data collection was focused on the lived experience and management of chronic cancer-related pain and a deep understanding of how the experience of chronic cancer-related pain shapes pain management choices. Results: The participants had a variety of primary cancer types and cancer pain syndromes. Three essential themes epitomized the experience of living with chronic cancer-related pain: invisible suffering at the cost of survival, an opioid paradox, and a lack of answers on what to expect and what might help. Conclusion and Implications: The results highlight an opportunity for pain self-management, education, and psychosocial interventions to optimize pain in cancer. Participants' experiences identify several opportunities to improve chronic cancer-related pain. Future efforts should prioritize access to multimodal pain treatments, high-quality communication, and expand clinicians' knowledge and skills to manage chronic pain.

A Pilot Qualitative Case Study of Women's Experiences with Fertility Awareness-Based Methods.

This pilot qualitative case study was able to elicit rich data enabling a description of how women went through the journey of achieving pregnancy using fertility awareness-based methods. Findings underscore that women preferred using natural ways to detect ovulation and would recommend other women to do so, but with healthcare providers' guidance. The findings of this case study can serve as a starting point to provide a framework to understand women's experiences of enduring trial and error with multiple fertility awareness-based methods before discovering their effective method. Findings emphasize the importance for healthcare providers to guide women in using fertility awareness-based methods.

Tracking Symptoms of Patients With Lymphedema Before and After Power-Assisted Liposuction Surgery.

PURPOSE: Lymphedema negatively impacts patients from a psychosocial standpoint and consequently affects patient's quality of life. Debulking procedures using power-assisted liposuction (PAL) are currently deemed an effective treatment for fat-dominant lymphedema and improves anthropometric measurements as well as quality of life. However, there have been no studies specifically evaluating changes in symptoms related to lymphedema after PAL. An understanding of how symptoms change after this procedure would be valuable for preoperative counseling and to guide patient expectations. METHODS: A cross-sectional study was performed in patients with extremity lymphedema who underwent PAL from January 2018 to December 2020 at a tertiary care facility. A retrospective chart review and follow-up phone survey were conducted to compare signs and symptoms related to lymphedema before and after PAL. RESULTS: Forty-five patients were included in this study. Of these, 27 patients (60%) underwent upper extremity PAL and 18 patients (40%) underwent lower extremity PAL. The mean follow-up time was 15.5±7.9 months. After PAL, patients with upper extremity lymphedema reported having resolved heaviness (44%), as well as improved achiness (79%) and swelling (78%). In patients with lower extremity lymphedema, they reported having improved all signs and symptoms, particularly swelling (78%), tightness (72%), and achiness (71%). CONCLUSIONS: In patients with fat-dominant lymphedema, PAL positively impacts patient-reported outcomes in a sustained fashion over time. Continuous surveillance of postoperative studies is required to elucidate factors independently associated with the outcomes found in our study. Moreover, further studies using a mixed method approach will help us better understand patient's expectations to achieve informed decision and adequate treatment goals.

Awareness of Disease Status Among Patients With Cancer: An Integrative Review.

BACKGROUND: As the quality of cancer care improves, oncology patients face a rapidly increasing number of treatment options. Thus, it is vital that they are full and active partners in the treatment decision-making process. Awareness of disease status has been investigated in the literature; it has been inconsistently conceptualized and operationalized. OBJECTIVE: The aim of this integrative review was to develop a conceptual definition and model of the awareness of disease status among patients with cancer. METHODS: Whittemore and Knafl's integrative review methodology guided this article. We obtained data through a systematic search of 8 databases. Key terms utilized were awareness, perception, truth disclosure, diagnosis, prognosis, terminal illness, status, neoplasm, and metastasis. Dates through January 2020 were searched to capture all relevant articles. Sixty-nine articles met inclusion criteria. RESULTS: The integrative review methodology guided the development of a conceptual definition and model. The concept of "awareness of disease status" was defined as the individual patient's understanding of being diagnosed and treated for cancer based on the multifactorial components of individual patient characteristics and contextually driven communication practices of healthcare providers. This understanding is dynamic and changes throughout the disease trajectory. CONCLUSION: These findings will inform consistency in the literature. Such consistency may improve person-centered clinical communication, care planning practices, and, ultimately, cancer-related outcomes. IMPLICATIONS FOR PRACTICE: With a greater understanding of the complexity of patients' awareness of disease status, nurses will be able to guide their patients to make informed decisions throughout their disease trajectory.

Losartan controls immune checkpoint blocker-induced edema and improves survival in glioblastoma mouse models.

Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and CD8+ T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment that disrupts the blood-tumor barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a "hot" tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions.

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.

The Role of Exercise Self-Efficacy in Exercise Participation Among Women With Persistent Fatigue After Breast Cancer: A Mixed-Methods Study.

OBJECTIVE: Survivors of breast cancer with persistent cancer-related fatigue (CRF) report less exercise participation compared with survivors of breast cancer without CRF. Although CRF predicts other domains of self-efficacy among survivors, the effect of CRF on exercise self-efficacy (ESE)-an important predictor of exercise participation-has not been quantified. This study examined the relationship between CRF, ESE, and exercise participation and explored the lived experience of engaging in exercise among survivors of breast cancer with persistent CRF. METHODS: Fifty-eight survivors of breast cancer (3.7 [SD = 2.4] years after primary treatment) self-reported CRF, ESE, and exercise participation (hours of moderate-intensity exercise per week). Regression and mediation analyses were conducted. Survivors who reported clinically significant CRF and weekly exercise were purposively sampled for 1-on-1 interviews (N = 11). Thematic analysis was performed across participants and within higher versus lower ESE subsets. RESULTS: Greater CRF predicted lower ESE (ß = -0.32) and less exercise participation (ß = -0.08). ESE mediated the relationship between CRF and exercise participation (ß = -0.05, 95% CI = -0.09 to -0.02). Qualitative data showed that survivors of breast cancer with higher ESE perceived exercise as a strategy to manage fatigue, described self-motivation and commitment to exercise, and had multiple sources of support. In contrast, survivors with lower ESE described less initiative to manage fatigue through exercise, greater difficulty staying committed to exercise, and less support. CONCLUSIONS: Survivors of breast cancer with persistent CRF may experience decreased ESE, which negatively influences exercise participation. Clinicians should screen for or discuss confidence as it relates to exercise and consider tailoring standardized exercise recommendations for this population to optimize ESE. This may facilitate more sustainable exercise participation and improve outcomes. IMPACT: This study highlights the behavioral underpinnings of CRF as a barrier to exercise. Individualized exercise tailored to optimize ESE may facilitate sustainable exercise participation among survivors of breast cancer with CRF. Strategies for clinicians to address ESE are described and future research is suggested. LAY SUMMARY: Women with fatigue after breast cancer treatment may have lower confidence about their ability to engage in exercise. Individually tailoring exercise to build confidence as it relates to exercise may result in more consistent exercise and better health-related outcomes.

[Interleukin-17A is closely correlated with the progression of renal epithelial-mesenchymal transition in spontaneously hypertensive rats].

OBJECTIVE: To explore the role of interleukin-17A (IL-17A) in renal epithelial- mesenchymal transition (EMT) in essential hypertensive nephropathy. METHODS: Four-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (control group) were both randomized into 4 groups (n=5) for observation at 4, 6, 10 and 30 weeks of age. Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry. The mRNA and protein expression levels of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining, respectively, and plasma levels of IL-17A were regularly detected using ELISA. RESULTS: At the age of 6 weeks, the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats (P < 0.05 or P < 0.01). At 30 weeks, renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats (P < 0.01). Compared with the WKY rats, the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks (P < 0.05 or 0.01) and higher α-SMA mRNA and protein expressions since 10 weeks of age (P < 0.05 or 0.01). In SHRs older than 10 weeks, renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin (r=-0.731, P < 0.05; r=-0.827, P < 0.01) and positively correlated with those of α-SMA (r=0.658, P < 0.05; r=0.968, P < 0.01). CONCLUSION: IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.

Corrigendum to 'A transcriptomic dataset evaluating the effect of radiotherapy injury on cells of skin and soft tissue' Data in Brief 41 (2022) 107828.

[This corrects the article DOI: 10.1016/j.dib.2022.107828.].

A WeChat-Based Rehabilitation Platform for Children and Adolescents with Congenital Heart Disease to Promote Cardiac FITness (HeartFIT): Protocol for a Mixed-Methods Strategy from Evidence-Based Design to Pilot Study.

Progress in medical and surgical care has tremendously improved the survival rates of children with congenital heart disease (CHD). However, reduced aerobic capacity and health-related issues remain a threaten to quality survival and prevention of related complications among children and adolescents with CHD. This research program aims to develop and evaluate a WeChat-based health platform (HeartFIT) to facilitate cardiac rehabilitation and promote physical fitness for this rapidly expanding young population. The study protocol describes the use of an iterative process of using a mixed-methods strategy to develop, refine, and pilot test the proposed HeartFIT platform. A sequential problem-solving process comprising four iterative phases with ongoing end-user input will be implemented. In phase 1, relevant literature was systematically reviewed (completed) and then child-parent dyads will be interviewed to understand the broad context and the requirements and considerations of the target population toward the WeChat-based rehabilitation platform. In phase 2, key features and priority functionalities for the platform will be ideated and refined, and a digital interactive prototype will be created. In phase 3, heuristic evaluation and three rounds of end-user testing will be conducted to ensure further refinement and usability of the prototype. In phase 4, a prospective pilot study will be performed to investigate the feasibility, acceptability, and preliminary efficacy of the developed platform over a 12-week intervention period. If HeartFIT intervention is feasible, acceptable, and demonstrates promising efficacy, an adequately powered randomized controlled trial (future work) will be deployed to test the real-world effectiveness of the intervention.

Psychometric Properties of the Spanish Version of Breast Cancer and Lymphedema Symptom Experience Index.

BACKGROUND: Lymphedema is a common late and chronic adverse effect of breast cancer treatment. This study aimed to translate and evaluate the psychometric properties of the BCLE-SEI Spanish version with Spanish-speaking breast cancer patients. METHOD: 286 patients were recruited (2018 to 2020), from the Hospital Universitario Central de Asturias. Data analysis included descriptive statistics; internal consistency and test-retest reliability; principal component analysis and exploratory factor analysis; average variance extracted; and receiver operating characteristic curves. RESULTS: No semantic modifications to items were needed. The scores of the instrument demonstrated excellent internal consistency (Cronbach´s alpha = .95-.97; McDonald´s omega = .96-.98) and test-retest reliability (r = .78-.87, n = 29). A significant difference was observed between the lymphedema group and non-lymphedema group (p < .001) in terms of total scale, symptom occurrence (p < .001), symptom distress in the physical-functional (p < .001), and psychosocial dimension (p < .001). Principal component analysis for symptom occurrence revealed a unidimensional factor and two factors were identified for symptom distress via exploratory factor analysis, the two of which explained 45.71% and 54.77% of the total sample variance, respectively. CONCLUSIONS: This study provided initial evidence to support the psychometric properties of the BCLE-SEI Spanish version.

A transcriptomic dataset evaluating the effect of radiotherapy injury on cells of skin and soft tissue.

Radiotherapy injury to cells of the skin and subcutaneous tissue is an inevitable consequence of external beam radiation for treatment of cancer. This sublethal injury to normal tissues plays a significant role in the development of fibrosis, lymphedema, impaired wound healing, and recurrent infections. To elucidate the transcriptional changes that occur in cells of the skin and soft tissues after radiotherapy injury, we performed genome-wide RNA-sequencing comparing irradiated cells (10Gy) with non-irradiated (0Gy) controls in normal human dermal fibroblasts, normal human keratinocytes, human microvascular endothelial cells, human dermal lymphatic endothelial cells, pericytes and adipose derived stem cell populations. These data are publicly available from the Gene Expression Omnibus database (accession number GSE184119). Further insights can be gained by comparing the mRNA signatures arising from radiation injury derived from these data to publicly available signatures from other studies involving similar or different tissue types. These global targets hold potential for manipulation to mitigate radiotherapy soft tissue injury.

Use of Dual-Energy X-Ray Absorptiometry to Assess Soft Tissue Composition in Breast Cancer Survivors With and Without Lymphedema.

Background: In patients with lymphedema (LE), in addition to hand dominance, between-group comparisons of interlimb soft tissue differences need to account for differences in whole-body adiposity, measured directly by dual energy X-ray absorptiometry (DXA) or indirectly by body mass index. No study has evaluated the effects of hand dominance and whole-body adiposity on limb composition in patients with LE. This study's purpose was to compare soft tissue composition of affected and unaffected limbs of women with breast cancer, who did and did not have LE, controlling for dominance and percent body fat. Methods and Results: Whole-body DXA scans were acquired and included measures of percent body fat, upper limb total mass, upper limb fat mass, and upper limb fat-free mass. Participants were classified into one of three groups: women without LE; women with only subjective LE; and women with objective signs of LE at the time of assessment. Differences among the LE groups were evaluated using analysis of variance (ANOVA) and Chi-square analyses. Analysis of covariance (ANCOVA) was used to control for percent body fat and for the affected limb dominance. Compared to women without LE, women with objective signs of LE have greater total limb mass, fat mass, and fat-free mass in their affected limbs, independent of affected side dominance and percent body fat. In addition, the interlimb differences in total mass, fat mass, and fat-free mass were greater for the women with objective signs of LE, compared to the other two groups. Conclusions: DXA is useful in identifying soft tissue changes in patients with LE. Given that limb circumferences measure only changes in limb volume and that bioimpedance provides estimates of extracellular fluid, DXA has the advantage of being able to estimate the volumes of specific tissues in the limb.