Extraction of artefactual MRS patterns from a large database using non-negative matrix factorization

Despite the success of automated pattern recognition methods in problems of human brain tumor diagnostic classification, limited attention has been paid to the issue of automated data quality assessment in the field of MRS for neuro-oncology. Beyond some early attempts to address this issue, the current standard in practice is MRS quality control through human (expert-based) assessment. One aspect of automatic quality control is the problem of detecting artefacts in MRS data. Artefacts, whose variety has already been reviewed in some detail and some of which may even escape human quality control, have a negative influence in pattern recognition methods attempting to assist tumor characterization. The automatic detection of MRS artefacts should be beneficial for radiology as it guarantees more reliable tumor characterizations, as well as the development of more robust pattern recognition-based tumor classifiers and more trustable MRS data processing and analysis pipelines. Feature extraction methods have previously been used to help distinguishing between good and bad quality spectra to apply subsequent supervised pattern recognition techniques. In this study, we apply feature extraction differently and use a variant of a method for blind source separation, namely Convex Non-Negative Matrix Factorization, to unveil MRS signal sources in a completely unsupervised way. We hypothesize that, while most sources will correspond to the different tumor patterns, some of them will reflect signal artefacts. The experimental work reported in this paper, analyzing a combined short and long echo time 1H-MRS database of more than 2000 spectra acquired at 1.5T and corresponding to different tumor types and other anomalous masses, provides a first proof of concept that points to the possible validity of this approach.Peer ReviewedPostprint (author's final draft

Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

Background There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-γ-2 (PPARγ2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13–18.5 years. Methods A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE ε3ε4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPARγ2 genotypes. Conclusion The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE ε3/ε4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.The AVENA study was supported by the Spanish Ministry of Health Instituto de Salud Carlos III (FIS PI021830), the Spanish Ministry of Health, FEDER-FSE funds FIS n° 00/0015, CSD grants 05/UPB32/0, 109/UPB31/03 and 13/UPB20/04, the Spanish Ministry of Education (AP-2004-2745; EX-2007-1124), scholarships from Panrico S.A., Madaus S.A. and Procter and Gamble S.A

Angiotensin-(1–7) and the G Protein-Coupled Receptor Mas Are Key Players in Renal Inflammation

Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1–7) by interacting with the G protein-coupled receptor Mas may also have important biological activities

Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death

This work was supported by Agencia Aragonesa para la Investigación y Desarrollo (ARAID), Ministerio de Economía y Competitividad (CTQ2013-44367-C2-2-P to R.H.-G.) and Diputación General de Aragón (DGA; B89 to R.H.-G.) and the EU Seventh Framework Programme (2007–2013) under BioStruct-X (grant agreement 283570 and BIOSTRUCTX 5186, to R.H.-G.). T.K.S. was supported by the Wellcome Trust grant 093228 and European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED).Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite’s growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.Publisher PDFPeer reviewe

Biogenesis and Dynamics of Mitochondria during the Cell Cycle: Significance of 3′UTRs

Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of β-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (ΔΨm) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of β-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3′UTR of the transcript. The 3′UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated β-F1-ATPase expression in human cancer

A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data

BackgroundThe clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal.Methodology/Principal FindingsNon-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification.Conclusions/SignificanceWe show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain tumor labeling from single-voxel spectroscopy data. We are confident that the proposed methodology has wider applicability for biomedical signal processing

Validity of Resting Energy Expenditure Predictive Equations before and after an Energy-Restricted Diet Intervention in Obese Women

Background We investigated the validity of REE predictive equations before and after 12-week energy-restricted diet intervention in Spanish obese (30 kg/m2>BMI<40 kg/m2) women. Methods We measured REE (indirect calorimetry), body weight, height, and fat mass (FM) and fat free mass (FFM, dual X-ray absorptiometry) in 86 obese Caucasian premenopausal women aged 36.7±7.2 y, before and after (n = 78 women) the intervention. We investigated the accuracy of ten REE predictive equations using weight, height, age, FFM and FM. Results At baseline, the most accurate equation was the Mifflin et al. (Am J Clin Nutr 1990; 51: 241–247) when using weight (bias:−0.2%, P = 0.982), 74% of accurate predictions. This level of accuracy was not reached after the diet intervention (24% accurate prediction). After the intervention, the lowest bias was found with the Owen et al. (Am J Clin Nutr 1986; 44: 1–19) equation when using weight (bias:−1.7%, P = 0.044), 81% accurate prediction, yet it provided 53% accurate predictions at baseline. Conclusions There is a wide variation in the accuracy of REE predictive equations before and after weight loss in non-morbid obese women. The results acquire especial relevance in the context of the challenging weight regain phenomenon for the overweight/obese population.The present study was supported by the University of the Basque Country (UPV 05/80), Social Foundation of the Caja Vital- Kutxa and by the Department of Health of the Government of the Basque Country (2008/111062), and by the Spanish Ministry of Science and Innovation (RYC-2010-05957)

A Broad Assessment of Factors Determining Culicoides imicola Abundance: Modelling the Present and Forecasting Its Future in Climate Change Scenarios

Bluetongue (BT) is still present in Europe and the introduction of new serotypes from endemic areas in the African continent is a possible threat. Culicoides imicola remains one of the most relevant BT vectors in Spain and research on the environmental determinants driving its life cycle is key to preventing and controlling BT. Our aim was to improve our understanding of the biotic and abiotic determinants of C. imicola by modelling its present abundance, studying the spatial pattern of predicted abundance in relation to BT outbreaks, and investigating how the predicted current distribution and abundance patterns might change under future (2011–2040) scenarios of climate change according to the Intergovernmental Panel on Climate Change. C. imicola abundance data from the bluetongue national surveillance programme were modelled with spatial, topoclimatic, host and soil factors. The influence of these factors was further assessed by variation partitioning procedures. The predicted abundance of C. imicola was also projected to a future period. Variation partitioning demonstrated that the pure effect of host and topoclimate factors explained a high percentage (>80%) of the variation. The pure effect of soil followed in importance in explaining the abundance of C. imicola. A close link was confirmed between C. imicola abundance and BT outbreaks. To the best of our knowledge, this study is the first to consider wild and domestic hosts in predictive modelling for an arthropod vector. The main findings regarding the near future show that there is no evidence to suggest that there will be an important increase in the distribution range of C. imicola; this contrasts with an expected increase in abundance in the areas where it is already present in mainland Spain. What may be expected regarding the future scenario for orbiviruses in mainland Spain, is that higher predicted C. imicola abundance may significantly change the rate of transmission of orbiviruses

Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial

Background The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. Methods/Design One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. Discussion Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.This study was supported by the Consejeria de Turismo, Comercio y Deporte (CTCD-201000019242-TRA), the Spanish Ministry of Science and Innovation (I + D + I DEP2010-15639, grants: BES-2009-013442, BES-2011-047133, RYC-2010-05957, RYC-2011-09011), the Swedish Heart-Lung Foundation (20090635), the Spanish Ministry of Education (AP-2009-3173), Granada Research of Excelence Initiative on Biohealth (GREIB), Campus BioTic, University of Granada, Spain and European University of Madrid. Escuela de Estudios Universitarios Real Madrid. 2010/04RM

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

BACKGROUND: The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant. METHODS: We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects. RESULTS: We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients. CONCLUSION: We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes