Impact of Oncotype DX testing on ER+ breast cancer treatment and survival in the first decade of use

Background: The Oncotype DX breast recurrence score has been introduced more than a decade ago to aid physicians in determining the need for systemic adjuvant chemotherapy in patients with early-stage, estrogen receptor (ER)+, lymph node-negative breast cancer. Methods: In this study, we utilized data from The Surveillance, Epidemiology, and End Results (SEER) Program to investigate temporal trends in Oncotype DX usage among US breast cancer patients in the first decade after the introduction of the Oncotype DX assay. Results: We found that the use of Oncotype DX has steadily increased in the first decade of use and that this increase is associated with a decreased usage of chemotherapy. Patients who utilized the Oncotype DX test tended to have improved survival compared to patients who did not use the assay even after adjusting for clinical variables associated with prognosis. In addition, chemotherapy usage in patients with high-risk scores is associated with significantly longer overall and breast cancer-specific survival compared to high-risk patients who did not receive chemotherapy. On the contrary, patients with low-risk scores who were treated with chemotherapy tended to have shorter overall survival compared to low-risk patients who forwent chemotherapy. Conclusion: We have provided a comprehensive temporal overview of the use of Oncotype DX in breast cancer patients in the first decade after Oncotype DX was introduced. Our results suggest that the use of Oncotype DX is increasing in ER+ breast cancer and that the Oncotype DX test results provide valuable information for patient treatment and prognosis

Systematic computational identification of prognostic cytogenetic markers in neuroblastoma

Background: Neuroblastoma (NB) is the most common extracranial solid tumor found in children. The frequent gain/loss of many chromosome bands in tumor cells and absence of mutations found at diagnosis suggests that NB is a copy number-driven cancer. Despite the previous work, a systematic analysis that investigates the relationship between such frequent gain/loss of chromosome bands and patient prognosis has yet to be implemented. Methods: First, we analyzed two NB CNV datasets to select chromosomal bands with a high frequency of gain or loss. Second, we applied a computational approach to infer sample-specific CNVs for each chromosomal band selected in step 1 based on gene expression data. Third, we applied univariate Cox proportional hazards models to examine the association between the resulting inferred copy number values (iCNVs) and patient survival. Finally, we applied multivariate Cox proportional hazards models to select chromosomal bands that remained significantly associated with prognosis after adjusting for critical clinical variables, including age, stage, gender, and MYCN amplification status. Results: Here, we used a computational method to infer the copy number variations (CNVs) of sample-specific chromosome bands from NB patient gene expression profiles. The resulting inferred CNVs (iCNVs) were highly correlated with the experimentally determined CNVs, demonstrating CNVs can be accurately inferred from gene expression profiles. Using this iCNV metric, we identified 58 frequent gain/loss chromosome bands that were significantly associated with patient survival. Furthermore, we found that 7 chromosome bands were still significantly associated with patient survival even when clinical factors, such as MYCN status, were considered. Particularly, we found that the chromosome band chr11p14 has high potential as a novel candidate cytogenetic biomarker for clinical use. Conclusion: Our analysis resulted in a comprehensive list of prognostic chromosome bands supported by strong statistical evidence. In particular, the chr11p14 gain event provided additional prognostic value in addition to well-established clinical factors, including MYCN status, and thereby represents a novel candidate cytogenetic biomarker with high clinical potential. Additionally, this computational framework could be readily extended to other cancer types, such as leukemia

Forward osmosis research trends in desalination and wastewater treatment: A review of research trends over the past decade

Issues of water scarcity and water security have driven the rapid development of various technologies to ensure water sustainability. The forward osmosis (FO) membrane process has been widely recognized as one of the more promising technologies to play an important role in alleviating the issues of water sustainability. Extensive research has been carried out worldwide to explore the potential of FO in desalination, water and wastewater treatment and reclamation. It is of the utmost importance to understand the topics of interest and research trends to further advance the development of FO process technology. In this study, a bibliometric analysis based on the Scopus database was carried out to identify and understand the global research trends of FO process based on 6 main analyses: basic growth trends, journals, countries, institutions, authors, and keywords. A total of 1462 article published between 1967-2018 were extracted from Scopus and used as the raw data for bibliometric analysis using VOSviewer software. The total number of FO articles has sharply increased since 2009 and stabilized at around 250 publications in the past three years. FO research started to diversify after the appearance of commercial FO membranes with improved characteristics, enabling the researchers to employ them for various application studies. Keywords analysis showed that the main directions of FO research could be categorized into three clusters: application of FO, membrane fouling study, and FO membrane synthesis. These bibliometric results provide a valuable reference and information on current research directions of FO for researchers and industry practitioners

Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine

<p>Abstract</p> <p>Background</p> <p>Bladder cancer is the sixth most common cancer in the world and the incidence is particularly high in southwestern Taiwan. Previous studies have identified several tumor-related genes that are hypermethylated in bladder cancer; however the DNA methylation profile of bladder cancer in Taiwan is not fully understood.</p> <p>Methods</p> <p>In this study, we compared the DNA methylation profile of multiple tumor suppressor genes (<it>APC</it>, <it>DAPK</it>, <it>E-cadherin</it>, <it>hMLH1</it>, <it>IRF8</it>, <it>p14</it>, <it>p15</it>, <it>RASSF1A</it>, <it>SFRP1 </it>and <it>SOCS-1</it>) in bladder cancer patients from different Chinese sub-populations including Taiwan (104 cases), Hong Kong (82 cases) and China (24 cases) by MSP. Two normal human urothelium were also included as control. To investigate the diagnostic potential of using DNA methylation in non-invasive detection of bladder cancer, degree of methylation of <it>DAPK</it>, <it>IRF8</it>, <it>p14</it>, <it>RASSF1A </it>and <it>SFRP1 </it>was also accessed by quantitative MSP in urine samples from thirty bladder cancer patients and nineteen non-cancer controls.</p> <p>Results</p> <p>There were distinct DNA methylation epigenotypes among the different sub-populations. Further, samples from Taiwan and China demonstrated a bimodal distribution suggesting that CpG island methylator phentotype (CIMP) is presented in bladder cancer. Moreover, the number of methylated genes in samples from Taiwan and Hong Kong were significantly correlated with histological grade (P < 0.01) and pathological stage (P < 0.01). Regarding the samples from Taiwan, methylation of <it>SFRP1</it>, <it>IRF8</it>, <it>APC </it>and <it>RASSF1A </it>were significantly associated with increased tumor grade, stage. Methylation of <it>RASSF1A </it>was associated with tumor recurrence. Patients with methylation of <it>APC </it>or <it>RASSF1A </it>were also significantly associated with shorter recurrence-free survival. For methylation detection in voided urine samples of cancer patients, the sensitivity and specificity of using any of the methylated genes (<it>IRF8</it>, <it>p14 </it>or <it>sFRP1</it>) by qMSP was 86.7% and 94.7%.</p> <p>Conclusions</p> <p>Our results indicate that there are distinct methylation epigenotypes among different Chinese sub-populations. These profiles demonstrate gradual increases with cancer progression. Finally, detection of gene methylation in voided urine with these distinct DNA methylation markers is more sensitive than urine cytology.</p

Metagenomic Characterization and Comparative Analysis of Removable Denture-Wearing and Non-Denture-Wearing Individuals in Healthy and Diseased Periodontal Conditions

Removable denture wearers are at an increased risk of developing periodontal diseases due to biofilm deposition and microbial colonization on the denture surface. This study aimed to characterize and compare the metagenomic composition of saliva in denture wearers with different periodontal statuses. Twenty-four community-dwelling elders were recruited and grouped into denture wearers with active periodontitis (APD), non-denture wearers with active periodontitis (APXD), denture wearers with stable periodontal health conditions (SPCD), and non-denture wearers with stable periodontal health conditions (SPCXD). Saliva samples were collected and underwent Type IIB restriction-site-associated DNA for microbiome (2bRAD-M) metagenomic sequencing to characterize the species-resolved microbial composition. Alpha diversity analysis based on the Shannon index revealed no significant difference between groups. Beta diversity analysis using the Jaccard distance matrix was nearly significantly different between denture-wearing and non-denture-wearing groups (p = 0.075). Some respiratory pathogens, including Streptococcus agalactiae and Streptococcus pneumoniae, were detected as the top 30 species in saliva samples. Additionally, LEfSe analysis revealed a substantial presence of pathogenic bacteria in denture groups. In the cohort of saliva samples collected from community-dwelling elders, a remarkable abundance of certain opportunistic pathogens was detected in the microbial community

Erectile Dysfunction Predicts Coronary Heart Disease in Type 2 Diabetes

ObjectivesWe examined the predictive power of erectile dysfunction (ED) on coronary heart disease (CHD) events in Chinese men with type 2 diabetes.BackgroundSubjects with diabetes are prone to develop cardiovascular complications. Erectile dysfunction is strongly associated with CHD in cross-sectional studies, but prospective data are lacking.MethodsA consecutive cohort of men with no clinical evidence of cardiovascular disease underwent comprehensive assessments for diabetic complications. Erectile dysfunction was defined according to the definition of the National Institutes of Health Consensus Conference 1992. Coronary heart disease events were censored with centralized territory-wide hospital databases in 2005.ResultsOf 2,306 subjects (age: 54.2 ± 12.7 years; follow-up: 4.0 [range 1.7 to 7.1] years), 26.7% had ED at baseline. The incidence of CHD events was higher in men with ED than those without (19.7/1,000 person-years, 95% confidence interval [CI] 14.3 to 25.2 person-years vs. 9.5/1,000 person-years, 95% CI 7.4 to 11.7 person-years). Men who developed CHD events were older; had a higher frequency of ED and microvascular complications; had longer duration of diabetes; and had higher blood pressure, total cholesterol, low-density lipoprotein cholesterol, and urinary albumin/creatinine ratio but lower high-density lipoprotein cholesterol and estimated glomerular filtration rate than those without CHD events. Erectile dysfunction remained an independent predictor for CHD events (hazard ratio 1.58, 95% CI 1.08 to 2.30, p = 0.018) after adjustment for other covariates along with age, duration of disease, and use of antihypertensive agents and albuminuria.ConclusionsIn type 2 diabetic men without clinically overt cardiovascular disease, the presence of ED predicts a new onset of CHD events. Symptoms of ED should be independently sought to identify high-risk subjects for comprehensive cardiovascular assessments

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms.Methods: We explored functional near-infrared spectroscopy (fNIRS) alongside a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer's disease (AD). In addition, a group of healthy controls (HC) was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD) took part in the present study.Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively); in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively); in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively). The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886) between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE) score] in MCI subjects uniquely.Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment.Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and hypoactivation in mild AD could reflect an inability to compensate. Future studies will investigate the fNIRS parameters with a larger sample size, and their validity as prognostic biomarkers of neurodegeneration