Miracle-dz/UniFAR-FTUs huggingface dataset:
The VEGF-634 G > C promoter polymorphism is associated with risk of gastric cancer

Background: Both TGF-β1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the TGFB1 and VEGF genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population. Methods: The risk associated with genotypes and haplotypes of four TGFB1 SNPs and four VEGF SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity. Results: Compared with the VEGF-634GG genotype, the -634CG genotype and the combined 634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other TGFB1 and VEGF SNPs was associated with risk of gastric cancer. Conclusion: Our data suggested that the VEGF-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies. Background Gastric cancer is one of the major causes of cancer-related deaths worldwide, although both incidence and mortality of gastric cancer have been declining in recent years [1]. In 2008, there were 21,500 new gastric cancer patients, and 10,880 patients died of this disease in the United States [2]. Epidemiological studies have identified many risk factors for gastric cancer, including older age, being a man, Helicobacter pylori (H. pylori) bacteria infection, diets high in smoked foods, salted fish and meats, and pickled vegetables, tobacco use and obesity [2]. Although about two-thirds of gastric cancer could be prevented by changing lifestyle and diet habits [3], the fact that some individuals develop gastric cancer while others do not when having similar exposures suggests that genetic factors may also play an important role in the etiology of gastric cancer. Published: 16 October 2009 BMC Gastroenterology 2009, 9:77 doi:10.1186/1471-230X-9-77 Received: 11 May 2009 Accepted: 16 October 2009 This article is available from: http://www.biomedcentral. com/1471-230X/9/77 © 2009 Guan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fast 3D migration-velocity analysis by wavefield extrapolation using the prestack exploding-reflector model

In areas of complex geology, migration-velocity estimation should use methods that describe the complexity of wavefield propagation, such as focusing and defocusing, multipathing, and frequency-dependent velocity sensitivity. Migration-velocity analysis by wavefield extrapolation has the ability to address these issues because, in contrast to ray-based methods, it uses wavefields as carriers of information. However, its high cost and lack of flexibility with respect to model parametrization and to target-oriented analysis have prevented its routine industrial use. We overcome those limitations by using new types of wavefields as carriers of information: the image-space generalized wavefields. These wavefields are synthesized from a prestack image computed with wavefield-extrapolation methods, using the prestack exploding-reflector model. Cost of migration-velocity analysis (MVA) by wavefield extrapolation is decreased because only a small number of image-space generalized wavefields are necessary to accur.
Improved Automated Radiosynthesis of [11C]PBR28

Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [11C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this study, we optimized the radiolabeling procedure of [11C]PBR28 for higher radiochemical yield, radiochemical purity, and specific activity, which can be easily translated to any automated module for clinical trials. Time-activity curves (TACs) derived from the dynamic PET imaging of male rhesus monkey brains demonstrated that [11C]PBR28 had suitable kinetics with radiotracer accumulation observed in the caudate, putamen, cerebellum, and frontal cortex region.
Imaging Surveillance After Primary Breast Cancer Treatment.

OBJECTIVE Current clinical guidelines are consistent in supporting annual mammography for women after treatment of primary breast cancer. Surveillance imaging beyond standard digital mammography, including digital breast tomosynthesis (DBT), breast ultrasound, and MRI, may improve outcomes. This article reviews the evidence on the performance and effectiveness of breast imaging modalities available for surveillance after treatment of sporadic unilateral primary breast cancer and identifies additional factors to be considered when selecting an imaging surveillance regimen. CONCLUSION Evidence review supports the use of mammography for surveillance after primary breast cancer treatment. Variability exists in guideline recommendations for surveillance initiation, interval, and cessation. DBT offers the most promise as a potential modality to replace standard digital mammography as a front-line surveillance test; a single published study to date has shown a significant decrease in recall rates compared with standard digital mammography alone. Most guidelines do not support the use of whole-breast ultrasound in breast cancer surveillance, and further studies are needed to define the characteristics of women who may benefit from MRI surveillance. The emerging evidence about surveillance imaging outcomes suggests that additional factors, including patient and imaging characteristics, tumor biology and gene expression profile, and choice of treatment, warrant consideration in selecting personalized posttreatment imaging surveillance regimens.
Dissection of transcriptional and cis‐regulatory control of differentiation in human pancreatic cancer

The histological grade of carcinomas describes the ability of tumor cells to organize in differentiated epithelial structures and has prognostic and therapeutic impact. Here, we show that differential usage of the genomic repertoire of transcriptional enhancers leads to grade‐specific gene expression programs in human pancreatic ductal adenocarcinoma (PDAC). By integrating gene expression profiling, epigenomic footprinting, and loss‐of‐function experiments in PDAC cell lines of different grade, we identified the repertoires of enhancers specific to high‐ and low‐grade PDACs and the cognate set of transcription factors acting to maintain their activity. Among the candidate regulators of PDAC differentiation, KLF5 was selectively expressed in pre‐neoplastic lesions and low‐grade primary PDACs and cell lines, where it maintained the acetylation of grade‐specific enhancers, the expression of epithelial genes such as keratins and mucins, and the ability to organize glandular epithelia in xenografts. The identification of the transcription factors controlling differentiation in PDACs will help clarify the molecular bases of its heterogeneity and progression.
Polymorphisms in DNA Repair Genes and Susceptibility to Glioma in a Chinese Population

The excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and X-ray repair cross-complementing group 1 (XRCC1) genes appear to protect mammalian cells from the harmful effects of ionizing radiation. We conducted a large case-control study to investigate the association of polymorphisms in ERCC1 C118T, ERCC1 C8092A, XRCC1 A194T, XRCC1 A194T, and XRCC3 C241T, with glioma risk in a Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped, using the MassARRAY IPLEX platform, in 443 glioma cases and 443 controls. Association analyses based on an χ2 test and binary logistic regression were performed to determine the odds ratio (OR) and a 95% confidence interval (95% CI) for each SNP. For XRCC1 Arg194Trp, the variant genotype T/T was strongly associated with a lower risk of glioma cancer when compared with the wild type C/C (OR = 2.45, 95% CI = 1.43–4.45). Individuals carrying the XRCC1 399A allele had an increased risk of glioma (OR = 1.33, 95% CI = 1.02–1.64). The XRCC3 241T/T genotype was associated with a strong increased glioma risk (OR = 3.78, 95% CI = 1.86–9.06). Further analysis of the interactions of two susceptibility-associated SNPs, XRCC1 Arg194Trp and XRCC3 Thr241Met, showed that the combination of the XRCC1 194T and XRCC3 241T alleles brought a large increase in glioma risk (OR = 2.75, 95% CI = 1.54–4.04). XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XRCC3 C241T, appear to be associated with susceptibility to glioma in a Chinese population.
mplications of post-perovskite transport properties for core – mantle dynamics

Recent evidence on perovskite to post-perovskite phase change in the lowermost mantle suggests that post-perovskite piles or lens should be present in the relatively cold downwelling areas, while the roots of the hot upwelling plumes consist of perovskite. Post-perovskite is often believed to be deformed predominantly by the dislocation creep and there are some hints that the activation parameters of the dislocation creep in post-perovskite induce lower viscosity than that of perovskite at the same pressure and temperature conditions. That can even result in a viscosity paradox in the lowermost mantle—viscosity in cold downwellings transformed to post-perovskite might be lower than the viscosity of warm perovskite plumes. Such a viscosity structure was indeed recently suggested by the geodynamical inversions of the geoid. Rheologically weak areas at the base of the subducted slabs may have important consequences for the slab deformation in the D′′. We investigate the dynamics of the cold slabs transformed to postperovskite in the lowermost mantle by means of the simulations of thermal convection in a 2D Cartesian model of the lower mantle with composite rheology including diffusion creep and dislocation creep. Different creep parameters are used for the perovskite lower mantle and for the post-perovskite lens (or layer) respectively. While perovskite is considered to be deformed via linear diffusion creep, postperovskite is modeled either as a constant viscosity material (with viscosity ranging from 1020 Pa s to 1023 Pa s) or it is deformed purely by the dislocation creep. The presence of the rheologically distinct postantle convection perovskite not only strongly influences the slab deformation above the core–mantle boundary (CMB) but also results in different dynamic regimes of the CMB region (characterised by, e.g., the different length scales of the upwelling plumes) depending on the creep parameters of post-perovskite. Further, the presence of very low viscosity lens or a layer above the CMB strongly enhances the CMB heat flux in the cold slab areas. According to the amount of post-perovskite present in the D′′ and the rheology of post-perovskite the heat flux across the CMB can vary considerably with time, which may have important man implications for the core–
The implications of human metabolic network topology for disease comorbidity

Most diseases are the consequence of the breakdown of cellular processes, but the relationships among genetic/epigenetic defects, the molecular interaction networks underlying them, and the disease phenotypes remain poorly understood. To gain insights into such relationships, here we constructed a bipartite human disease association network in which nodes are diseases and two diseases are linked if mutated enzymes associated with them catalyze adjacent metabolic reactions. We find that connected disease pairs display higher correlated reaction flux rate, corresponding enzyme-encoding gene coexpression, and higher comorbidity than those that have no metabolic link between them. Furthermore, the more connected a disease is to other diseases, the higher is its prevalence and associated mortality rate. The network topology-based approach also helps to uncover potential mechanisms that contribute to their shared pathophysiology. Thus, the structure and modeled function of the human metabolic network can provide insights into disease comorbidity, with potentially important consequences for disease diagnosis and prevention.
Dehydration in Hospital-Admitted Stroke Patients: Detection, Frequency, and Association

Background and Purpose— We aimed to determine the frequency of dehydration, risk factors, and associations with outcomes at hospital discharge after stroke. Methods— We linked clinical data from stroke patients in 2 prospective hospital registers with routine blood urea and creatinine results. Dehydration was defined by a blood urea-to-creatinine ratio >80. Results— Of 2591 patients registered, 1606 (62%) were dehydrated at some point during their admission. Independent risk factors for dehydration included older age, female gender, total anterior circulation syndrome, and prescribed diuretics (all P<0.001). Patients with dehydration were significantly more likely be dead or dependent at hospital discharge than those without (&khgr;2=170.5; degrees of freedom=2; P<0.0001). Conclusions— Dehydration is common and associated with poor outcomes. Further work is required to establish if these associations are causal and if preventing or treating dehydration improves outcomes.
Feel the Noise: Relating Individual Differences in Auditory Imagery to the Structure and Function of Sensorimotor Systems

Humans can generate mental auditory images of voices or songs, sometimes perceiving them almost as vividly as perceptual experiences. The functional networks supporting auditory imagery have been described, but less is known about the systems associated with interindividual differences in auditory imagery. Combining voxel-based morphometry and fMRI, we examined the structural basis of interindividual differences in how auditory images are subjectively perceived, and explored associations between auditory imagery, sensory-based processing, and visual imagery. Vividness of auditory imagery correlated with gray matter volume in the supplementary motor area (SMA), parietal cortex, medial superior frontal gyrus, and middle frontal gyrus. An analysis of functional responses to different types of human vocalizations revealed that the SMA and parietal sites that predict imagery are also modulated by sound type. Using representational similarity analysis, we found that higher representational specificity of heard sounds in SMA predicts vividness of imagery, indicating a mechanistic link between sensory- and imagery-based processing in sensorimotor cortex. Vividness of imagery in the visual domain also correlated with SMA structure, and with auditory imagery scores. Altogether, these findings provide evidence for a signature of imagery in brain structure, and highlight a common role of perceptual–motor interactions for processing heard and internally generated auditory information.
Rapid quantitative profiling of complex microbial populations

Diverse and complex microbial ecosystems are found in virtually every environment on earth, yet we know very little about their composition and ecology. Comprehensive identification and quantification of the constituents of these microbial communities—a ‘census’—is an essential foundation for understanding their biology. To address this problem, we developed, tested and optimized a DNA oligonucleotide microarray composed of 10 462 small subunit (SSU) ribosomal DNA (rDNA) probes (7167 unique sequences) selected to provide quantitative information on the taxonomic composition of diverse microbial populations. Using our optimized experimental approach, this microarray enabled detection and quantification of individual bacterial species present at fractional abundances of <0.1% in complex synthetic mixtures. The estimates of bacterial species abundance obtained using this microarray are similar to those obtained by phylogenetic analysis of SSU rDNA sequences from the same samples—the current ‘gold standard’ method for profiling microbial communities. Furthermore, probes designed to represent higher order taxonomic groups of bacterial species reliably detected microbes for which there were no species-specific probes. This simple, rapid microarray procedure can be used to explore and systematically characterize complex microbial communities, such as those found within the human body.
Differential Regulation of Pituitary Hormone Secretion and Gene Expression by Thyrotropin-Releasing Hormone. A Role for Mitogen-Activated Protein Kinase Signaling Cascade in Rat Pituitary GH3 Cells1

Abstract We examined the possible involvement of mitogen-activated protein (MAP) kinase activation in the secretory process and gene expression of prolactin and growth hormone. Thyrotropin-releasing hormone (TRH) rapidly stimulated the secretion of both prolactin and growth hormone from GH3 cells. Secretion induced by TRH was not inhibited by 50 μM PD098059, but was completely inhibited by 1 μM wortmannin and 10 μM KN93, suggesting that MAP kinase does not mediate the secretory process. Stimulation of GH3 cells with TRH significantly increased the mRNA level of prolactin, whereas expression of growth hormone mRNA was largely attenuated. The increase in prolactin mRNA stimulated by TRH was inhibited by addition of PD098059, and the decrease in growth hormone mRNA was also inhibited by PD098059. Transfection of the cells with a pFC-MEKK vector (a constitutively active MAP kinase kinase kinase), significantly increased the synthesis of prolactin and decreased the synthesis of growth hormone. These data taken together indicate that MAP kinase mediates TRH-induced regulation of prolactin and growth hormone gene expression. Reporter gene assays showed that prolactin promoter activity was increased by TRH and was completely inhibited by addition of PD098059, but that the promoter activity of growth hormone was unchanged by TRH. These results suggest that TRH stimulates both prolactin and growth hormone secretion, but that the gene expressions of prolactin and growth hormone are differentially regulated by TRH and are mediated by different mechanisms.
A wavelet-based neural model to optimize and read out a temporal population code

It has been proposed that the dense excitatory local connectivity of the neo-cortex plays a specific role in the transformation of spatial stimulus information into a temporal representation or a temporal population code (TPC). TPC provides for a rapid, robust, and high-capacity encoding of salient stimulus features with respect to position, rotation, and distortion. The TPC hypothesis gives a functional interpretation to a core feature of the cortical anatomy: its dense local and sparse long-range connectivity. Thus far, the question of how the TPC encoding can be decoded in downstream areas has not been addressed. Here, we present a neural circuit that decodes the spectral properties of the TPC using a biologically plausible implementation of a Haar transform. We perform a systematic investigation of our model in a recognition task using a standardized stimulus set. We consider alternative implementations using either regular spiking or bursting neurons and a range of spectral bands. Our results show that our wavelet readout circuit provides for the robust decoding of the TPC and further compresses the code without loosing speed or quality of decoding. We show that in the TPC signal the relevant stimulus information is present in the frequencies around 100 Hz. Our results show that the TPC is constructed around a small number of coding components that can be well decoded by wavelet coefficients in a neuronal implementation. The solution to the TPC decoding problem proposed here suggests that cortical processing streams might well consist of sequential operations where spatio-temporal transformations at lower levels forming a compact stimulus encoding using TPC that are subsequently decoded back to a spatial representation using wavelet transforms. In addition, the results presented here show that different properties of the stimulus might be transmitted to further processing stages using different frequency components that are captured by appropriately tuned wavelet-based decoders.
Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.
Kawasaki disease incidence in children and adolescents: an observational study in primary care.

BACKGROUND Kawasaki disease is reported to be increasing in incidence and is the commonest childhood cause of acquired heart disease in the Western world. AIM To determine the current UK incidence of Kawasaki disease across childhood and adolescence; and investigate trends over time and season. DESIGN AND SETTING An observational, descriptive study in the UK. METHOD The Health Improvement Network (THIN) database of primary healthcare records was searched for codes or text indicating Kawasaki disease. Identified records were compared with a study case definition and a date of onset was assigned to cases. The incidence, age/sex distribution, and trend in seasonal and temporal distribution were estimated (2008-2012). RESULTS A total of 110 episodes of Kawasaki disease in 109 children were identified from 3.9 million person-years observation. The incidence of Kawasaki disease was 2.8 per 100 000 person-years (95% confidence interval [CI] = 2.3 to 3.4) when aged <20 years; 9.1 (95% CI = 7.3 to 11.2) aged <5 years, and 3.0 per 100 000 (95% CI = 2.0 to 4.3) across the age groups when possible cases were included. More cases were identified in males (55%) with one-fifth of cases diagnosed after 5 years of age. There was no statistically significant trend in incidence over the study years (P = 0.10 adjusted for sex and month), or between seasons (P = 0.65 adjusted for year and sex). CONCLUSION Although the incidence of Kawasaki disease remains low and has stabilised in the UK, GPs should recognise that the condition occurs throughout childhood and across the seasons.