Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymorphisms in the Matrix Metalloproteinase-9 Promoters and Susceptibility to Glial Tumors in Turkey.

AIM Evidence suggests an association between MMP-9 functional gene polymorphisms and several tumors. The aim of this study was to investigate the possible role of single-nucleotide polymorphisms (SNP) at MMP-9 R279Q A/G, P574R G/C and R668Q G/A and R668Q (rs17577) genotypes with glial tumors in Turkey. MATERIAL AND METHODS The present series consisted of tissue samples obtained from 100 cancer-free controls and 100 patients who had undergone glial tumor resection from 2007 to 2011 at the Cerrahpasa Medical Faculty of Istanbul University. Blood samples were collected to extract the genomic deoxyribonucleic acid (DNA) of each subject by polymerase chain reaction (PCR) and DNA sequencing. The genotypes of MMP-9 P574R, R279Q and R668Q SNPs were determined by using the PCR-RFLP assay. Genotypic distributions between patient and control groups were compared for correlations with glial tumor occurrence. RESULTS SNPs in MMP-9 were not found to be significantly associated with glial tumor risk among participants except R279Q (G-G) which showed high risk only in multivariate analysis (OR adjusted, 3.15 95% CI, 1.10-9.01). The comparisons between the grade of tumor and the genotypic polymorphisms also showed no significant associations in the case group (all p values > 0.05). CONCLUSION The current study showed a significant association between the R279Q G/G polymorphism and formation of glial tumor in advanced age. Changed protein features may cause triggering of some subcellular mechanisms that may have a role in activating oncogenic processes over the years. These data add to the growing epidemiological and experimental evidence that MMP-9 may play a role in glial tumors.
Prognostic factors and outcomes in anaplastic gliomas: An institutional experience

Abstract Background: There is lack of clear evidence and treatment guidelines for anaplastic gliomas (AGs) with very few studies focusing exclusively on these patients. The aim of the study was to analyze the clinical profile and survival in these patients. Materials and Methods: Patients of AGs treated with radiation and concurrent ± adjuvant chemotherapy from January 2010 to December 2015 were analyzed. Statistical analysis was done using SPSS version 20 software. Results: A total of 100 patients were included in the study. The median age was 35 years (range 6–68 years). Eighty-four patients had follow-up details and were included for survival analysis. The 5-year overall survival (OS) was 58%. Age, presentation with seizures, and focal neurological deficit were not found to significantly influence survival. The 5-year survival for oligodendroglioma and astrocytoma was 69% and 52%, respectively. Patients with Karnofsky Performance Score (KPS) of ≥70 had a significantly better 5-year OS (65%) as compared to those with KPS <70 (33%) (P = 0.000). The use of adjuvant temozolomide (TMZ) showed longer 5-year OS of 67.7% compared to 36% in patients who did not receive adjuvant chemotherapy (P = 0.018). Patients receiving both concurrent and adjuvant TMZ showed longer 5-year OS (68.5% vs. 40%, P = 0.010). Twenty-two patients had recurrence with average time to recurrence being 37 months. Fourteen patients underwent salvage surgery and two patients received reirradiation. Conclusions: OS significantly correlated with KPS and receipt of concurrent and adjuvant chemotherapy with TMZ. Therefore, adjuvant radiation with concurrent and adjuvant TMZ should be the standard of care for AGs.
Cerebral circulatory and metabolic effects of hypotension produced by deep halothane anaesthesia

Hypotension to a mean blood pressure of 33 mmHg for periods of 70 to 187 minutes was induced by increasing the inspired halothane concentration in 11 baboons which were already anaesthetized with 0·5% halothane, nitrous oxide, and oxygen. During hypotension, cerebral blood flow, measured by Xenon clearance and by a carotid electromagnetic flowmeter, decreased by more than half, and sagittal sinus oxygen saturation was 46%. Cerebral oxygen uptake fell from 5·15 to 3·56 ml. /100 g/min at this deeper level of halothane anaesthesia. Cerebral hyperaemia developed after hypotension in those animals which regained a mean blood pressure greater than 70 mmHg. Acidbase measurements on CSF from the cisterna magna revealed no metabolic acidosis during or after hypotension. In all four animals with intact autoregulation before hypotension, this was absent or impaired afterwards.
Legume intake and risk of prostate cancer: a meta-analysis of prospective cohort studies

Previous studies regarding the relationship between legume intake and risk of prostate cancer have reported inconsistent results. We conducted a meta-analysis of prospective cohort studies to summarize evidence on this association. A systematic literature search of articles published through June 2016 was performed using PubMed and Web of Science databases. The combined relative risk (RR) with its 95% confidence interval (CI) for the highest versus the lowest intake of legumes was calculated with a random-effects model. Dose-response meta-analysis was also performed for the studies that provided at least three levels of legume consumption. Ten articles (eight cohorts) reporting 281,034 individuals and 10,234 incident cases were identified. The individuals with high consumption of legumes compared with the reference group experienced a significantly reduced risk for developing prostate cancer (RR: 0.85 [95% CI 0.75−0.96], P = 0.010). Moderate heterogeneity of RRs was observed across these studies (P = 0.064 for heterogeneity, I2 = 45.8 %). Dose-response meta-analysis indicated that the risk of prostate cancer reduced by 3.7% (95% CI 1.5%−5.8%) for each 20 grams per day increment of legume intake. In conclusion, the results from this meta-analysis suggest that a high intake of legumes is associated with a low incidence of prostate cancer.
Genetic and environmental influences on eating behavior: the Swedish Young Male Twins Study.

BACKGROUND Eating behavior may be implicated in the increasing prevalence of overweight and obesity, presumably in relation to easy access to energy-dense and highly palatable foods. OBJECTIVE The aim of the present study was to disentangle genetic and environmental influences on eating behavior in a population-based cohort of male twins. DESIGN The study included 326 dizygotic and 456 monozygotic male twin pairs aged 23-29 y from Sweden. The revised 21-item version of the Three-Factor Eating Questionnaire (TFEQ-R21) was used to assess eating behavior. This validated instrument consists of 3 dimensions: cognitive restraint, emotional eating, and uncontrolled eating. Structural equation modeling was used to estimate the heritability of eating behavior. RESULTS Cognitive restraint was the only TFEQ-R21 scale that significantly correlated with BMI (r = 0.39, P < 0.0001). The best-fitted models gave a heritability of 59% (95% CI: 52%, 66%) for cognitive restraint, 60% (95% CI: 52%, 67%) for emotional eating, and 45% (95% CI: 36%, 53%) for uncontrolled eating. CONCLUSIONS These results show the great importance of genetic factors in the eating behavior of a large, unselected population of young adult male twins. Nonshared environmental factors were also important, whereas shared environmental factors did not contribute to eating behavior.
In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone

Several indolylquinone analogues of perezone, a natural sesquiterpene quinone, were characterized in this work by theoretical methods. In addition, some physicochemical, toxicological and metabolic properties were predicted using bioinformatics software. The predicted physicochemical properties are in agreement with the solubility and cLogP values, the penetration across the cell membrane, and absorption values, as well as with a possible apoptosis-activated mechanism of cytotoxic action. The toxicological predictions suggest no mutagenic, tumorigenic or reproductive effects of the four target molecules. Complementarily, the results of a performed docking study show high scoring values and hydrogen bonding values in agreement with the cytotoxicity IC50 value ranking, i.e., indolylmenadione > indolylperezone > indolylplumbagine > indolylisoperezone. Consequently, it is possible to suggest an appropriate apoptotic pathway for each compound. Finally, potential metabolic pathways of the molecules were proposed.
Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules. CUR is isolated from the root of turmeric (Curcuma longa). CUR is currently used in the treatment of many disorders, especially in those involving an inflammatory process. CUR and modified derivatives have been shown to have potent anti-cancer effects, especially on cancer stem cells (CSC). BBR is also isolated from various plants (e.g., Coptis chinensis) and has been used for centuries in traditional medicine to treat diseases such as adult- onset diabetes. Understanding the benefits of these and other nutraceuticals may result in approaches to improve human health.
Homocysteine and folate as risk factors for dementia and Alzheimer disease.

BACKGROUND In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results. OBJECTIVE We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population. DESIGN A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12. RESULTS Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 micromol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (< or = 11.8 nmol/L) were also associated with an increased risk of both dementia (1.87; 95% CI: 1.21, 2.89; P = 0.005) and AD (1.98; 95% CI: 1.15, 3.40; P = 0.014), whereas the association was not significant for vitamin B-12. CONCLUSIONS Elevated plasma tHcy concentrations and low serum folate concentrations are independent predictors of the development of dementia and AD.
Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Significance Reactive oxygen species (ROS) production is induced by multiple environmental stresses in various organisms. In plants, ROS transduce local and systemic signaling for adaptation and tolerance to these stresses. Here we show that red clover necrotic mosaic virus (RCNMV), a plant positive-strand RNA [(+)RNA] virus, hijacks the host’s ROS-generating machinery during infection. An RCNMV replication protein associates with host ROS-generating machinery and triggers intracellular ROS bursts. These bursts are required for robust viral RNA replication. We further show that another (+)RNA virus, brome mosaic virus, also depends on ROS for replication. This study represents an example of diversion of a plant stress-resilience system for robust virus replication. As sessile organisms, plants have to accommodate to rapid changes in their surrounding environment. Reactive oxygen species (ROS) act as signaling molecules to transduce biotic and abiotic stimuli into plant stress adaptations. It is established that a respiratory burst oxidase homolog B of Nicotiana benthamiana (NbRBOHB) produces ROS in response to microbe-associated molecular patterns to inhibit pathogen infection. Plant viruses are also known as causative agents of ROS induction in infected plants; however, the function of ROS in plant–virus interactions remains obscure. Here, we show that the replication of red clover necrotic mosaic virus (RCNMV), a plant positive-strand RNA [(+)RNA] virus, requires NbRBOHB-mediated ROS production. The RCNMV replication protein p27 plays a pivotal role in this process, redirecting the subcellular localization of NbRBOHB and a subgroup II calcium-dependent protein kinase of N. benthamiana (NbCDPKiso2) from the plasma membrane to the p27-containing intracellular aggregate structures. p27 also induces an intracellular ROS burst in an RBOH-dependent manner. NbCDPKiso2 was shown to be an activator of the p27-triggered ROS accumulations and to be required for RCNMV replication. Importantly, this RBOH-derived ROS is essential for robust viral RNA replication. The need for RBOH-derived ROS was demonstrated for the replication of another (+)RNA virus, brome mosaic virus, suggesting that this characteristic is true for plant (+)RNA viruses. Collectively, our findings revealed a hitherto unknown viral strategy whereby the host ROS-generating machinery is diverted for robust viral RNA replication.
Feeding frequency and type of isotope tracer do not affect direct estimates of lysine oxidation in growing pigs.

Oxidation contributes to the inefficiency of lysine utilization for protein deposition. The influences of feeding frequency and type of isotope tracer on estimated lysine oxidation were studied in growing pigs fed lysine-limiting diets. Yorkshire gilts (n = 11) weighing 40-45 kg were fitted with venous catheters. They were fed, in 3 or 8 equal meals daily, a purified diet based on casein and cornstarch. Lysine intake limited the pigs' protein deposition to 70% of their potential. After a 5-d N-balance period, lysine oxidation was estimated by a primed, constant 26-h infusion of [1-14C]L-lysine and [6-3H]L-lysine. Feeding frequency and type of tracer did not affect lysine oxidation (P > 0.1). Increasing feeding frequency from 3 to 8 times daily reduced the variance and fluctuation of lysine oxidation by 46 and 30%, respectively. The mean lysine oxidation, as a fraction of the true ileal digestible lysine intake, was 9.2% based on the free lysine specific radioactivity (SRA) in plasma, 20.1% based on free lysine SRA in liver and 21.8% calculated from N-balance data. On the basis of liver free lysine SRA, tracer dilution methods and N-balance data give similar quantitative estimates of lysine oxidation (P > 0.10). Isotope tracer studies that cover one or more complete feeding cycles, i.e., feeding-to-feeding periods, can be used to obtain valid daily lysine oxidation values.
Plasma retinol is a major determinant of vitamin A utilization in rats.

We studied relationships among vitamin A intake, liver levels of vitamin A, plasma retinol concentrations and the irreversible utilization of vitamin A. To supplement existing data, we first used model-based compartmental analysis to determine vitamin A utilization and other kinetic parameters in male Sprague-Dawley rats that had adequate liver vitamin A stores ( approximately 9000 nmol) and were fed a diet containing low levels of vitamin A. Plasma retinol kinetics were monitored for 43 d after administration of [3H]retinol-labeled plasma to rats consuming approximately 23 (Group 1, n = 6) or approximately 4.2 (Group 2, n = 6) nmol vitamin A/d. Data for plasma tracer vs. time and for tracer lost irreversibly by the end of the experiment, were fit to a three-compartment model in which plasma retinol exchanges with vitamin A in two kinetically distinct extravascular compartments. Irreversible utilization rates ( approximately 41 nmol/d) were similar to those for rats that are in vitamin A balance, suggesting that, when liver vitamin A stores are adequate, utilization rate is not decreased to compensate for a low vitamin A intake. Multiple linear regression analysis was then used to relate these and previously collected data (total, 62 rats) on vitamin A intake (4. 2-49 nmol/d), plasma retinol concentration (1.4-2.5 micromol/L) and liver vitamin A level (1.2-11,000 nmol) to vitamin A utilization (disposal rate, 4.2-68 nmol/d). A significant relationship (R2(adj) = 0.93) was found for the equation [disposal rate (nmol/d) = -0.720 (nmol/d) + 0.844 (d-1). (plasma retinol; nmol) + 0.00139 (d-1). (liver vitamin A; nmol) + 0.220. (vitamin A intake; nmol/d)]. Plasma retinol accounted for 92% of the variability in disposal rate (vs. 5% for liver vitamin A and 3% for vitamin A intake). We conclude that plasma retinol is a main determinant of the irreversible utilization of vitamin A in rats with low to moderate vitamin A intake.
Metabotropic glutamate receptors depress vagal and aortic baroreceptor signal transmission in the NTS.

We sought to determine whether metabotropic glutamate receptors contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in the nucleus of the solitary tract (NTS) in vivo. In α-chloralose-anesthetized rabbits, we determined the number of extracellular action potentials synaptically evoked by low (1 Hz)- or high-frequency vagal (3-20 Hz) or aortic depressor nerve (ADN) (6-80 Hz) stimulation and postsynaptically evoked by the ionotropic glutamate receptor agonist α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The metabotropic glutamate receptor agonist (2 S,1' S,2' S)-2-(carboxycyclopropyl)glycine (L-CCG-I) attenuated NTS responses monosynaptically evoked by 1-Hz vagus stimulation by 34% ( n = 25; P = 0.011), while augmenting AMPA-evoked responses by 64% ( n = 17; P = 0.026). The metabotropic glutamate receptor antagonist α-methyl-4-phosphonophenylglycine (MPPG) did not affect NTS responses to low-frequency vagal stimulation ( n = 11) or AMPA ( n = 10) but augmented responses to high-frequency stimulation by 50% ( n= 25; P = 0.0001). MPPG also augmented NTS responses to high-frequency ADN stimulation by 35% ( n = 9; P = 0.048) but did not affect responses to low-frequency stimulation ( n = 9) or AMPA ( n = 7). The results suggest that metabotropic glutamate receptors, presumably at presynaptic sites, contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in NTS.
Exercise cardiac magnetic resonance to differentiate athlete’s heart from structural heart disease

Aims The distinction between left ventricular (LV) dilation with mildly reduced LV ejection fraction (EF) in response to regular endurance exercise training and an early cardiomyopathy is a frequently encountered and difficult clinical conundrum. We hypothesized that exercise rather than resting measures would provide better discrimination between physiological and pathological LV remodelling and that preserved exercise capacity does not exclude significant LV damage. Methods and results We prospectively included 19 subjects with LVEF between 40 and 52%, comprising 10 ostensibly healthy endurance athletes (EA-healthy) and nine patients with dilated cardiomyopathy (DCM). In addition, we recruited five EAs with a region of subepicardial LV. Receiver operating characteristic fibrosis (EA-fibrosis). Cardiac magnetic resonance (CMR) imaging was performed at rest and during supine bicycle exercise. Invasive afterload measures were obtained to enable calculations of biventricular function relative to load (an estimate of contractility). In DCM and EA-fibrosis subjects there was diminished augmentation of LVEF (5 ± 6% vs. 4 ± 3% vs. 14 ± 3%; P = 0.001) and contractility [LV end-systolic pressure-volume ratio, LVESPVR; 1.4 (1.3-1.6) vs. 1.5 (1.3-1.6) vs. 1.8 (1.7-2.7); P < 0.001] during exercise relative to EA-healthy. Receiver-operator characteristic curves demonstrated that a cut-off value of 11.2% for ΔLVEF differentiated DCM and EA-fibrosis patients from EA-healthy [area under the curve (AUC) = 0.92, P < 0.001], whereas resting LVEF and VO2max were not predictive. The AUC value for LVESPVR ratio was similar to that of ΔLVEF. Conclusions Functional cardiac evaluation during exercise is a promising tool in differentiating healthy athletes with borderline LVEF from those with an underlying cardiomyopathy. Excellent exercise capacity does not exclude significant LV damage.
Worldwide burden of cervical cancer in 2008.

BACKGROUND The knowledge that persistent human papillomavirus infection is the main cause of cervical cancer has resulted in the development of assays that detect nucleic acids of the virus and prophylactic vaccines. Up-to-date and reliable data are needed to assess impact of existing preventive measures and to define priorities for the future. MATERIALS AND METHODS Best estimates on cervical cancer incidence and mortality are presented using recently compiled data from cancer and mortality registries for the year 2008. RESULTS There were an estimated 530,000 cases of cervical cancer and 275,000 deaths from the disease in 2008. It is the third most common female cancer ranking after breast (1.38 million cases) and colorectal cancer (0.57 million cases). The incidence of cervical cancer varies widely among countries with world age-standardised rates ranging from <1 to >50 per 100,000. Cervical cancer is the leading cause of cancer-related death among women in Eastern, Western and Middle Africa; Central America; South-Central Asia and Melanesia. The highest incidence rate is observed in Guinea, with ∼6.5% of women developing cervical cancer before the age of 75 years. India is the country with the highest disease frequency with 134,000 cases and 73 000 deaths. Cervical cancer, more than the other major cancers, affects women <45 years. CONCLUSIONS In spite of effective screening methods, cervical cancer continues to be a major public health problem. New methodologies of cervical cancer prevention should be made available and accessible for women of all countries through well-organised programmes.