A Bayesian Methodology for Estimation for Sparse Canonical Correlation

It can be challenging to perform an integrative statistical analysis of multi-view high-dimensional data acquired from different experiments on each subject who participated in a joint study. Canonical Correlation Analysis (CCA) is a statistical procedure for identifying relationships between such data sets. In that context, Structured Sparse CCA (ScSCCA) is a rapidly emerging methodological area that aims for robust modeling of the interrelations between the different data modalities by assuming the corresponding CCA directional vectors to be sparse. Although it is a rapidly growing area of statistical methodology development, there is a need for developing related methodologies in the Bayesian paradigm. In this manuscript, we propose a novel ScSCCA approach where we employ a Bayesian infinite factor model and aim to achieve robust estimation by encouraging sparsity in two different levels of the modeling framework. Firstly, we utilize a multiplicative Half-Cauchy process prior to encourage sparsity at the level of the latent variable loading matrices. Additionally, we promote further sparsity in the covariance matrix by using graphical horseshoe prior or diagonal structure. We conduct multiple simulations to compare the performance of the proposed method with that of other frequently used CCA procedures, and we apply the developed procedures to analyze multi-omics data arising from a breast cancer study

Verrucous carcinoma of the vulva: patterns of care and treatment outcomes.

Background: Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. Aims: The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. Methods and results: Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. OS was assessed with Kaplan–Meier curves and the log-rank test. Construction of a Cox model compared survival after controlling for confounding variables. The reported incidence of SCC of the vulva has significantly increased since 2004 (p \u3c .0001). In contrast, the incidence of VC has remained stable (p = .344) since 2004. Compared to SCC, VC was significantly more likely to be diagnosed in older women (p \u3c .0001) and treated with surgery alone (p \u3c .0001). However, on propensity score weighted analysis there was a trend toward improved 5-year OS in women with VC compared to those with SCC (63.4% vs. 57.7%, p = .0794). Multivariable Cox survival analysis showed an improvement in OS in VC patients treated with both primary site and regional lymph node surgery compared to primary site surgery alone (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.46–0.97, p = .0357). Conclusion: Verrucous carcinoma is more likely to present in older women. Regional lymph node surgery in addition to primary site surgery significantly improves OS in VC patients

Stereotactic body radiation therapy (SBRT) of adrenal gland metastases in oligometastatic and oligoprogressive disease

BACKGROUND: Stereotactic body radiation therapy (SBRT) as a form of noninvasive treatment that is becoming increasingly used to manage cancers with adrenal gland metastases. There is a paucity of data on safety and efficacy of this modality. The aim of the study was to evaluate the safety and efficacy of adrenal gland SBRT in oligometastatic and oligoprogressive disease. MATERIALS AND METHODS: In this retrospective study, we performed a single-institution analysis of 26 adrenal lesions from 23 patients with oligometastatic or oligoprogressive disease treated from 2013 to 2019 with the goal of achieving durable local control. Palliative cases were excluded. Radiation dosimetry data was collected. Kaplan Meier product estimator and Cox proportional hazards regression analysis were used for statistical analysis. RESULTS: The median dose was 36 Gy in 3 fractions (range: 24–50 Gy and 3–6 fractions) with a median biologically effective dose (BED10) of 72 (range: 40–100). 1-year local control rate was 80% and median local control was not achieved due to a low number of failures. 1- and 2-year overall survival rates were 66% and 32%. Toxicity was mild with only one case of grade 2 nausea and no grade 3–5 toxicity. Higher neutrophil to lymphocyte ratio was associated with worse overall survival and a trend toward worse progression-free survival. In addition, worse performance status and lower BED10 were associated with worse survival. No such association could be shown for primary tumor location, histology, size or stage. CONCLUSION: Adrenal SBRT for oligometastatic or oligoprogressive disease is a safe and effective form of treatment

The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study

Interstitial cystitis/bladder pain syndrome (ICBPS) may be related to an altered genitourinary microbiome. Our aim was to compare the vaginal and urinary microbiomes between premenopausal women with ICBPS and unaffected controls. This cross-sectional study screened premenopausal women with an O'Leary-Sant questionnaire (ICBPS if score ≥6 on either index; controls <6 on both). Women completed questionnaires on health characteristics, pelvic floor symptoms (OABq, PFDI-20), body image (mBIS), and sexual function (PISQ-IR). Bacterial genomic DNA was isolated from vaginal and clean-catch urinary specimens; the bacterial 16 rRNA gene was sequenced and analyzed using the QIIME pipeline. We performed UniFrac analysis (β-diversity) and generated Chao1 estimator (richness) and Simpson index (richness and evenness) values. We analyzed 23 ICBPS and 18 non-ICBPS patients. ICBPS patients had increased vaginal deliveries, BMI, and public insurance as well as worsened OAB-q, PFDI-20, mBIS, and PISQ-IR domain scores. Lactobacilli was the most abundant genus in both cohorts, and anaerobic or fastidious predominance was similar between groups (p = 0.99). For both the urine and vagina specimens, Chao1 and Simpson indices were similar between ICBPS and unaffected women. Weighted and unweighted UniFrac analyses showed no differences between groups. A significant correlation existed between the urinary and vaginal Simpson indices in ICBPS women, but not in unaffected women. Premenopausal women with ICBPS, despite worsened socioeconomic indicators and pelvic floor function, were not found to have significantly different urinary and vaginal microbiomes compared to women without ICBPS

Adipose-Derived Stromal Vascular Fraction Cell Effects on a Rodent Model of Thin Endometrium

<div><p>Endometrial dysfunction affects approximately 1% of infertile women, and there is currently no standard therapy for improving fertility treatment outcomes in these patients. In our study, we utilized a rodent model of thin endometrium to test whether intrauterine application of adipose-derived stromal vascular fraction cells (SVF) could improve morphological and physiological markers of endometrial receptivity. Using anhydrous ethanol, endometrial area and gland density were significantly reduced in our model of thin endometrium. Application of SVF was associated with a 29% reduction in endometrial vascular endothelial growth factor (VEGF) expression and significant increases in uterine artery systolic/diastolic velocity ratios and resistance index values, suggesting reduced diastolic microvascular tone. However, no significant improvements in endometrial area or gland density were observed following SVF treatment. 3D confocal imaging demonstrated poor engraftment of SVF cells into recipient tissue, which likely contributed to the negative results of this study. We suspect modified treatment protocols utilizing adjuvant estrogen and/or tail vein cell delivery may improve SVF retention and therapeutic response in subsequent studies. SVF is an easily-obtainable cell product with regenerative capability that may have a future role in the treatment of infertile women with endometrial dysfunction.</p></div

Representative examples of uterine horn cross sections in the third estrus phase following intrauterine instillation of either phosphate-buffered saline (PBS) (A and B) or ethanol (C and D).

<p>Gross differences in endometrial area and gland density are apparent. Scale bars = 500 μm (A) and 250 μm (B).</p

Graphs of mean endometrial areas (A) and median gland densities (B) between individual experimental groups (left) and collective sham and injured groups (right).

<p>Significant differences were observed between collective sham and injured groups (asterisks). Error bars represent standard deviation (A) and Q1, Q3 (B).</p

(A) Cultured stromal vascular fraction (SVF) cells viewed under bright field microscope at 10x magnification. (B) Fluorescent imaging demonstrates green fluorescent protein (GFP+) signal from SVF cells. Scale bar = 100 μm. (C) Intrauterine instillation procedures were performed with proximal and distal hemostatic clamps in place to isolate each uterine horn. (D) Protocol timeline demonstrates the approximate schedule of injury, treatment, and analysis.

<p>Exact dates were dependent on individual estrous cycles.</p