Modifying the false discovery rate procedure based on the information theory under arbitrary correlation structure and its performance in high-dimensional genomic data.

BACKGROUND: Controlling the False Discovery Rate (FDR) in Multiple Comparison Procedures (MCPs) has widespread applications in many scientific fields. Previous studies show that the correlation structure between test statistics increases the variance and bias of FDR. The objective of this study is to modify the effect of correlation in MCPs based on the information theory. We proposed three modified procedures (M1, M2, and M3) under strong, moderate, and mild assumptions based on the conditional Fisher Information of the consecutive sorted test statistics for controlling the false discovery rate under arbitrary correlation structure. The performance of the proposed procedures was compared with the Benjamini-Hochberg (BH) and Benjamini-Yekutieli (BY) procedures in simulation study and real high-dimensional data of colorectal cancer gene expressions. In the simulation study, we generated 1000 differential multivariate Gaussian features with different levels of the correlation structure and screened the significance features by the FDR controlling procedures, with strong control on the Family Wise Error Rates. RESULTS: When there was no correlation between 1000 simulated features, the performance of the BH procedure was similar to the three proposed procedures. In low to medium correlation structures the BY procedure is too conservative. The BH procedure is too liberal, and the mean number of screened features was constant at the different levels of the correlation between features. The mean number of screened features by proposed procedures was between BY and BH procedures and reduced when the correlations increased. Where the features are highly correlated the number of screened features by proposed procedures reached the Bonferroni (BF) procedure, as expected. In real data analysis the BY, BH, M1, M2, and M3 procedures were done to screen gene expressions of colorectal cancer. To fit a predictive model based on the screened features the Efficient Bayesian Logistic Regression (EBLR) model was used. The fitted EBLR models based on the screened features by M1 and M2 procedures have minimum entropies and are more efficient than BY and BH procedures. CONCLUSION: The modified proposed procedures based on information theory, are much more flexible than BH and BY procedures for the amount of correlation between test statistics. The modified procedures avoided screening the non-informative features and so the number of screened features reduced with the increase in the level of correlation.

Prediction of Normal Tissue Complication Probability (NTCP) After Radiation Therapy Using Imaging and Molecular Biomarkers and Multivariate Modelling.

The aim of this study was to design a predictive radiobiological model of normal brain tissue in low-grade glioma following radiotherapy based on imaging and molecular biomarkers. Fifteen patients with primary brain tumors prospectively participated in this study and underwent radiation therapy. Magnetic resonance imaging (MRI) was obtained from the patients, including T1- and T2-weighted imaging and diffusion tensor imaging (DTI), and a generalized equivalent dose (gEUD) was calculated. The radiobiological model of the normal tissue complication probability (NTCP) was performed using the variables gEUD; axial diffusivity (AD) and radial diffusivity (RD) of the corpus callosum; and serum protein S100B by univariate and multivariate logistic regression XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium (2018). Changes in AD, RD, and S100B from baseline up to the 6 months after treatment had an increasing trend and were significant in some time points (P-value < 0.05). The model resulting from RD changes in the 6 months after treatment was significantly more predictable of necrosis than other univariate models. The bivariate model combining RD changes in Gy40 dose-volume and gEUD, as well as the trivariate model obtained using gEUD, RD, and S100B, had a higher predictive value among multivariate models at the sixth month of the treatment. Changes in RD diffusion indices and in serum protein S100B value were used in the early-delayed stage as reliable biomarkers for predicting late-delayed damage (necrosis) caused by radiation in the corpus callosum. Current findings could pave the way for intervention therapies to delay the severity of damage to white matter structures, minimize cognitive impairment, and improve the quality of life of patients with low-grade glioma.

Evaluation of the gene encoding carnitine transporter (OCTN2/SLC22A5) expression in human breast cancer and its association with clinicopathological characteristics.

BACKGROUND: Fatty acid oxidation (FAO) is a major energy-generating process in the mitochondria and supports proliferation, growth, and survival of cancer cells. L-Carnitine is an essential co-factor for carrying long-chain fatty acids into the mitochondria. The entry of l-carnitine across cell membrane is regulated by OCTN2 (SLC22A5). Thus, it can plays a significant role in the mitochondrial fatty acid oxidation. This study aimed to evaluate the OCTN2 expression and its association with clinicopathological characteristics in breast cancer. METHODS: In this work, OCTN2 was examined in 54 pairs of fresh samples of breast cancer (BC) and adjacent noncancerous tissue using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC). The IHC approach was also used to investigate the expression of additional clinicopathological features. RESULTS: The present research findings revealed that the relative expression of OCTN2 in BC tissues was substantially higher than the adjacent normal tissues. This up-regulation was correlated positively with tumor size and Ki-67 and negatively with the progesterone receptor (PR) status, providing evidence of the opposite effects of OCTN2 and PR on tumor development. CONCLUSION: The study shows that the OCTN2 expression in BC patients may be used as a prognostic biomarker and a tumor oncogene. As a result, it could be considered a possible therapeutic target. Nevertheless, the significance of the findings needs to be confirmed by further studies.

The Impact of Incentive Spirometry on Shoulder Tip Pain in Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

BACKGROUND: Shoulder pain is among the early postlaparoscopic symptoms related to carbon dioxide used for pneumoperitoneum, which remains in the abdominal cavity. Therefore, incentive spirometry (IS) is a novel technique to alleviate this pain following laparoscopic cholecystectomy (LC). The present study was designed to investigate if the use of IS after LC would relieve shoulder tip pain, and determine the amount of postoperative opioid analgesics utilized. MATERIALS AND METHODS: This randomized clinical trial was conducted on patients who were clinically diagnosed with cholecystitis, and underwent LC. Accordingly, group I patients (n=42) received IS (including 10 deep breaths with a spirometer in sitting or semisitting positions) in full consciousness every 2 hours starting at 2 hours after surgery, but group II patients (n=42) did not have respiratory physiotherapy. The postoperative shoulder pain after the surgery was further evaluated by a numerical rating scale (NRS). RESULTS: At 4, 8, 12, 24, and 48 hours following LC, the NRS pain scores significantly reduced in group I compared with group II. In addition, the results of the repeated measures analysis of variance indicated significantly lower NRS pain scores within the first 48 hours after LC in group I compared with group II. Consequently, the study findings showed a significantly higher percentage of cases in group II, requiring postoperative analgesics, in comparison with group I. CONCLUSIONS: IS decreased the severity of shoulder tip pain after LC with no complications. Thus, IS may be considered as a viable alternative to other laparoscopic interventions. However, still further studies are necessary to evaluate its efficacy compared with other techniques.

Smokeless Tobacco Use in Iran: A Systematic Review.

BACKGROUND: Smokeless tobacco (ST) use is one of the most important public health problems in Southeast Asia. The use of these substances increases the incidence of some cancers and other diseases. The purpose of this review study was to investigate on ST use in Iran. METHODS: A literature search was conducted on PubMed, Google Scholar, and three national databases [Scientific Information Database (SID), IranMedex, and IranDoc] based on the standard search strategy. FINDINGS: Most consumer people lived in Sistan and Baluchestan Province (Zahedan and Chabahar Cities) and Golestan Province, Iran. ST use rates ranged from 11.0% to 45.7% among college students in Sistan and Baluchestan (Zahedan and Chabahar) and Golestan. There are various types of ST consumed in Iran that have been mentioned in various articles, including Pan, Gutka, Nass, Naswar, Biti, and Supari. CONCLUSION: Most studies on ST have been conducted in Sistan and Baluchestan and Golestan Provinces and we need more research for other provinces. Consumption by women is a warning and a threat to women's health in the future. Further studies will be needed to find out more precisely the prevalence of consumption in Iran.