From space to biomedicine: Enabling biomarker data science in the cloud.

NASA's Jet Propulsion Laboratory (JPL) is advancing research capabilities for data science with two of the National Cancer Institute's major research programs, the Early Detection Research Network (EDRN) and the Molecular and Cellular Characterization of Screen-Detected Lesions (MCL), by enabling data-driven discovery for cancer biomarker research. The research team pioneered a national data science ecosystem for cancer biomarker research to capture, process, manage, share, and analyze data across multiple research centers. By collaborating on software and data-driven methods developed for space and earth science research, the biomarker research community is heavily leveraging similar capabilities to support the data and computational demands to analyze research data. This includes linking diverse data from clinical phenotypes to imaging to genomics. The data science infrastructure captures and links data from over 1600 annotations of cancer biomarkers to terabytes of analysis results on the cloud in a biomarker data commons known as "LabCAS". As the data increases in size, it is critical that automated approaches be developed to "plug" laboratories and instruments into a data science infrastructure to systematically capture and analyze data directly. This includes the application of artificial intelligence and machine learning to automate annotation and scale science analysis.

Acute temozolomide induced liver injury: mixed type hepatocellular and cholestatic toxicity.

Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT): 632 IU/L (normal range 0-40); aspartate aminotransferase(AST): 554 IU/L (normal range 5-34); alkaline phosphatase(ALP): 1143 IU/L (normal range 40-150); γ-glutamyl transpeptidase(GGT): 514 IU/L (normal range 9-64 IU/L); total bilirubin: 15.1 mg/dL (normal range 0-1.2); direct bilirubin: 13.2 mg/dL and prothrombin time(PT): 13.5 s, with international normalized ratio (INR): 1.1 (normal range 0.8-1.2). His liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that TMZ was the probable cause of the acute hepatitis. His liver function tests gradually normalized in 2 months after discontinuation of the drug. In susceptible individuals, TMZ use may lead to acute mixed type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established. (Acta gastro-enterol. belg., 2016, 79, 363-365).

Aromatase inhibitors decrease radiation-induced lung fibrosis: Results of an experimental study.

PURPOSE: In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. MATERIALS AND METHODS: 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. RESULTS: Mean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. CONCLUSIONS: In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.

Acute temozolomide induced liver injury : Mixed type hepatocellular and cholestatic toxicity.

Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15.1 mg/dL (normal range 0-1.2) ; direct bilirubin : 13.2 mg/dL and prothrombin time(PT) : 13.5 s, with international normalized ratio (INR) : 1.1 (normal range 0.8-1.2). His liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that TMZ was the probable cause of the acute hepatitis. His liver function tests gradually normalized in 6 months after discontinuation of the drug. In susceptible individuals, TMZ use may lead to acute mixed type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established. (Acta gastroenterol. belg., 2016, 79, 487-489).

Δ9-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta.

OBJECTIVE: In this study, we investigated the possible effect of Δ(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus. MATERIAL AND METHODS: Type 2 diabetes was induced with 65 mg/kg STZ, 15 minute later 85 mg/kg NIC was given intraperitoneally (i.p.) to rats. Three days after diabetes induction, THC (3 mg/kg/day, i.p.) was given for 7 days to diabetic rats. Body weight and plasma glucose levels of rats were measured in all groups before and at the end of 3 weeks after diabetes induction. Acetylcholine (Ach) and sodium nitroprusside (SNP) potency and maximum relaxant effects were calculated on aortic rings pre-contracted with noradrenaline (NA). RESULTS: At the end of 3 weeks, blood glucose levels of diabetic group significantly increased in comparison with the control group. Increased plasma glucose levels were significantly decreased by the treatment of THC. Ach induced relaxation was impaired whereas endothelium-independent relaxation to SNP was unaffected on isolated diabetic rat aorta. THC treatment enhanced Ach induced relaxation on diabetic rat aortas. DISCUSSION: These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.

Effects of omega-3 polyunsaturated fatty acid supplementation on serum fetuin-A levels in type 2 diabetic patients.

Fetuin-A is an endogenous inhibitor of the insulin-stimulated insulin receptor tyrosine kinase recently shown that high levels of circulating fetuin-A are associated with insulin resistance in humans suggesting that fetuin-A may represent a novel mechanism involved in the pathophysiology of type 2 diabetes (T2DM). Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to reduce triglyceride levels, but their impact on glycemic control are not well known. The aim of this study to determine the effects of omega-3 PUFA supplementation on fetuin-A and glycemic control in patients with type 2 diabetes mellitus. 40 T2DM patients (17 males/23 females; aged 39-65 years) were included in the study. Serum fetuin-A levels and metabolic and biochemical profiles were measured before (baseline) and two months after n-3 PUFA supplementations (1.2 g/day). Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay. Our results indicated that serum fetuin-A, fasting glucose, HbA1c and triglyceride levels were significantly decreased after supplementation (P<0.02, P<0.001, P<0.02 and P<0.01, respectively). At baseline, serum fetuin-A levels were correlated with HbA1c (r:-0.391, P<0.04). A significant positive correlation between fetuin-A and both triglycerides (r: 0.343, P<0.05) and total cholesterol (r: 0.330, P<0.05) and negative correlation between fetuin-A and fasting glucose (r: -0.405, P<0.01) were found after the supplementations. When performed multiply regression analysis, we found that serum fetuin-a levels were related with triglyceride levels (r: 0.351, P<0.01) at baseline and HbA1c levels (r: 0.344, P<0.04) after the supplementation. Based on the results, it thought that omega-3 PUFA intake decreases serum fetuin-A levels and serum fetuin-A is associated with plasma lipids and glycemic controls in type 2 diabetic patients. Further studies are required to resolve the question.

Factors affecting intraocular pressure measured by noncontact tonometer.

PURPOSE: To investigate the mean values of intraocular pressure (IOP) measured with noncontact tonometer (NCT) and evaluate the factors that may affect IOP. METHODS: A total of 850 subjects who were admitted to our clinic between March 2005 and February 2006 were recruited for the study. Subjects having blepharitis, conjunctivitis, corneal diseases, glaucoma suspicion, or glaucoma were not accepted to the study. All subjects were questioned about systemic diseases. IOP measurement with NCT and central corneal thickness (CCT) with ultrasound pachymetry were performed for each patient between 9 and 11 AM. RESULTS: The mean ages of 367 (43.2%) male subjects and 483 (56.8%) female subjects were 43.9+/-18.1 and 40.7+/-18.0 years +/- SD, respectively. Since right and left eye IOP, CCT, and keratometric values were significantly correlated, right eye values were used for statistical purposes. Mean IOP values in males and females were 13.2+/-3.0 and 13.5+/-2.9 mmHg, respectively. Mean CCT values were 552.5+/-34.7 mum for males and 550.1+/-34.3 mum for females. In multiple regression analysis, IOP was found to be associated with gender, refractive error, CCT, and the presence of diabetes mellitus (DM). CONCLUSIONS: Gender, CCT, the presence of DM, and refractive error may be significantly associated with IOP in this particular population.

Factors influencing central corneal thickness in a Turkish population.

PURPOSE: The aim of this study is to find out the central corneal thickness (CCT) values for a Turkish patient group and to investigate the possible influences of age, sex, IOP, refractive status, keratometry readings, systemic disorders (hypertension, diabetes mellitus, hyperlipidemia, heart disease and asthma) on CCT values. MATERIALS AND METHODS: Six hundred twenty five subjects (276 male (44%), 349 female (56%)) of ages 6 to 88 years were recruited. Subjects who had corneal diseases, purulent conjunctivitis or blepharitis were excluded. Refraction and keratometry readings were made by MRK-3100 premium auto-ref/keratometer, IOP was measured by Reichert AT-555 auto noncontact pneumotonometer. RESULTS: Mean age was 44.1 +/- 16.6 years +/- SD for male subjects, 41.0 +/- 16.9 for females. Mean CCT +/- SD values for male was 552.2 +/- 35.9 microm, for female was 552.3 +/- 35.4 microm, respectively. There was no significant difference between right and left eye CCT values for both genders. Age and CCT was not correlated for the whole study group but there was a slight negative correlation in male subjects. IOP and CCT had moderately significant correlation for males and females. There was a slight significant correlation between Kh-Kv and CCT values for the whole group. In a multivariate regression model only Kv values seemed to affect CCT values. DISCUSSION: There are studies showing the variation of CCT values among different nations and ethnicities. There is no agreement about the relationship between age, IOP, Kh-Kv, spherical equivalence of refractive error, systemic disorders, menopause and CCT. In our study CCT was correlated with Kh-Kv and IOP in correlation analysis but in multivariate regression analysis only Kv appeared to influence corneal thickness.