vgaraujov/thesis-chile huggingface dataset:
Dark-blood late gadolinium enhancement without additional magnetization preparation

Abstract Background This study evaluates a novel dark-blood late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) method, without using additional magnetization preparation, and compares it to conventional bright-blood LGE, for the detection of ischaemic myocardial scar. LGE is able to clearly depict myocardial infarction and macroscopic scarring from viable myocardium. However, due to the bright signal of adjacent left ventricular blood, the apparent volume of scar tissue can be significantly reduced, or even completely obscured. In addition, blood pool signal can mimic scar tissue and lead to false positive observations. Simply nulling the blood magnetization by choosing shorter inversion times, leads to a negative viable myocardium signal that appears equally as bright as scar due to the magnitude image reconstruction. However, by combining blood magnetization nulling with the extended grayscale range of phase-sensitive inversion-recovery (PSIR), a darker blood signal can be achieved whilst a dark myocardium and bright scar signal is preserved. Methods LGE was performed in nine male patients (63 ± 11y) using a PSIR pulse sequence, with both conventional viable myocardium nulling and left ventricular blood nulling, in a randomized order. Regions of interest were drawn in the left ventricular blood, viable myocardium, and scar tissue, to assess contrast-to-noise ratios. Maximum scar transmurality, scar size, circumferential scar angle, and a confidence score for scar detection and maximum transmurality were also assessed. Bloch simulations were performed to simulate the magnetization levels of the left ventricular blood, viable myocardium, and scar tissue. Results Average scar-to-blood contrast was significantly (p < 0.001) increased by 99% when nulling left ventricular blood instead of viable myocardium, while scar-to-myocardium contrast was maintained. Nulling left ventricular blood also led to significantly (p = 0.038) higher expert confidence in scar detection and maximum transmurality. No significant changes were found in scar transmurality (p = 0.317), normalized scar size (p = 0.054), and circumferential scar angle (p = 0.117). Conclusions Nulling left ventricular blood magnetization for PSIR LGE leads to improved scar-to-blood contrast and increased expert confidence in scar detection and scar transmurality. As no additional magnetization preparation is used, clinical application on current MR systems is readily available without the need for extensive optimizations, software modifications, and/or additional training.
Development and characterization of microsatellite markers in Gaultheria pumila Lf. (Ericaceae)

Abstract Background Polymorphic microsatellite markers were developed for Gaultheria pumila (Ericaceae) to evaluate genetic diversity and population structure within its native range in Chile. This is a very important Ericaceae endemic to Chile with a large commercial potential. Its resistance to different abiotic conditions makes it a valuable target for genetic improvement. Results Ten polymorphic simple sequence repeat (SSR) loci were isolated from Gaultheria pumila using new-generation 454 FLX Titanium pyrosequencing technology. The mean number of alleles per locus ranged from 2 to 4. Observed and expected heterozygosity ranged from 0.00 to 1.0 and 0.00 to 0.64, respectively. Conclusions From 10 SSR markers developed for G. pumila, 9 markers are promising candidates for analyzing genetic variation within or between natural populations of G. pumila and other species from the same genus.
Is L-methionine a trigger factor for Alzheimer’s-like neurodegeneration?: Changes in Aβ oligomers, tau phosphorylation, synaptic proteins, Wnt signaling and behavioral impairment in wild-type mice

Abstract Background L-methionine, the principal sulfur-containing amino acid in proteins, plays critical roles in cell physiology as an antioxidant and in the breakdown of fats and heavy metals. Previous studies suggesting the use of L-methionine as a treatment for depression and other diseases indicate that it might also improve memory and propose a role in brain function. However, some evidence indicates that an excess of methionine can be harmful and can increase the risk of developing Type-2 diabetes, heart diseases, certain types of cancer, brain alterations such as schizophrenia, and memory impairment. Results Here, we report the effects of an L-methionine-enriched diet in wild-type mice and emphasize changes in brain structure and function. The animals in our studypresented 1) higher levels of phosphorylated tau protein, 2) increased levels of amyloid-β (Aβ)-peptides, including the formation of Aβ oligomers, 3) increased levels of inflammatory response,4) increased oxidative stress, 5) decreased level of synaptic proteins, and 6) memory impairment and loss. We also observed dysfunction of the Wnt signaling pathway. Conclusion Taken together, the results of our study indicate that an L-methionine-enriched diet causes neurotoxic effects in vivo and might contribute to the appearance of Alzheimer’s-like neurodegeneration.
Amyloid-B-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the AB peptide. Implications for the pathogenesis of Alzheimer's disease

Abstract The presence of amyloid-β (Aβ) deposits in selected brain regions is a hallmark of Alzheimer's disease (AD). The amyloid deposits have "chaperone molecules" which play critical roles in amyloid formation and toxicity. We report here that treatment of rat hippocampal neurons with Aβ-acetylcholinesterase (Aβ-AChE) complexes induced neurite network dystrophia and apoptosis. Moreover, the Aβ-AChE complexes induced a sustained increase in intracellular Ca2+ as well as a loss of mitochondrial membrane potential. The Aβ-AChE oligomers complex also induced higher alteration of Ca2+ homeostasis compared with Aβ-AChE fibrillar complexes. These alterations in calcium homeostasis were reversed when the neurons were treated previously with lithium, a GSK-3β inhibitor; Wnt-7a ligand, an activator for Wnt Pathway; and an N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), demonstrating protective roles for activation of the Wnt signaling pathway as well as for NMDA-receptor inhibition. Our results indicate that the Aβ-AChE complexes enhance Aβ-dependent deregulation of intracellular Ca2+ as well as mitochondrial dysfunction in hippocampal neurons, triggering an enhanced damage than Aβ alone. From a therapeutic point of view, activation of the Wnt signaling pathway, as well as NMDAR inhibition may be important factors to protect neurons under Aβ-AChE attack.
An assessment of the Chilean National Examination of Orthopaedic Surgery

Abstract Background The Chilean National Examination of Orthopaedic Surgery (EMNOT) has been administered since 2009. It was developed to determine whether individual residents are meeting minimal knowledge standards at the end of their training programs. Methods We performed a retrospective evaluation of the EMNOT for all years it has been administered (2009–2015). The test was analyzed for content, taxonomy of questions asked (1: direct recall; 2: diagnosis; 3: evaluation/decision-making), residents’ performance, difficulty index and discrimination index. Results During the years of EMNOT administration, the most frequently tested areas have been pediatric orthopaedics (22.9 %), spine (13.8 %), general orthopaedics (13.8 %) and musculoskeletal trauma (9.9 %). A significant increase in questions with images was observed, as well as a significant decrease in the percentage of Type 1 and an increase in Type 3 questions. The Difficulty Index showed a medium level of difficulty for all years the examination has been administered. The Discrimination Index showed good discrimination in 2009, fair discrimination from 2010 through 2012, and excellent discrimination from 2013 through 2015. Conclusion The EMNOT has evolved over several years to include better quality questions, better discrimination, and a more representative distribution of questions covering the different orthopaedic sub-specialties. This examination represents an effective instrument for quality assurance of orthopaedic residency programs in Chile.
Development of phytase-expressing chlamydomonas reinhardtii for monogastric animal nutrition

Abstract Background In plant-derived animal feedstuffs, nearly 80 % of the total phosphorus content is stored as phytate. However, phytate is poorly digested by monogastric animals such as poultry, swine and fish, as they lack the hydrolytic enzyme phytase; hence it is regarded as a nutritionally inactive compound from a phosphate bioavailability point of view. In addition, it also chelates important dietary minerals and essential amino acids. Therefore, dietary supplementation with bioavailable phosphate and exogenous phytases are required to achieve optimal animal growth. In order to simplify the obtaining and application processes, we developed a phytase expressing cell-wall deficient Chlamydomonas reinhardtii strain. Results In this work, we developed a transgenic microalgae expressing a fungal phytase to be used as a food supplement for monogastric animals. A codon optimized Aspergillus niger PhyA E228K phytase (mE228K) with improved performance at pH 3.5 was transformed into the plastid genome of Chlamydomonas reinhardtii in order to achieve optimal expression. We engineered a plastid-specific construction harboring the mE228K gene, which allowed us to obtain high expression level lines with measurable in vitro phytase activity. Both wild-type and cell-wall deficient strains were selected, as the latter is a suitable model for animal digestion. The enzymatic activity of the mE228K expressing lines were approximately 5 phytase units per gram of dry biomass at pH 3.5 and 37 °C, similar to physiological conditions and economically competitive for use in commercial activities. Conclusions A reference basis for the future biotechnological application of microalgae is provided in this work. A cell-wall deficient transgenic microalgae with phytase activity at gastrointestinal pH and temperature and suitable for pellet formation was developed. Moreover, the associated microalgae biomass costs of this strain would be between US$5 and US$60 per ton of feedstuff, similar to the US$2 per ton of feedstuffs of commercially available phytases. Our data provide evidence of phytate-hydrolyzing microalgae biomass for use as a food additive without the need for protein purification.
An evidence-based approach to identify aging-related genes in Caenorhabditis elegans

Abstract Background Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C. elegans. Results We developed a semantic knowledge base for aging by integrating data about C. elegans genes from WormBase with data about 2005 human and model organism genes from GenAge and 149 genes from GenDR, and with the Bio2RDF network of linked data for the life sciences. Using HyQue (a Semantic Web tool for hypothesis-based querying and evaluation) to interrogate this knowledge base, we examined 48,231 C. elegans genes for their role in modulating lifespan and aging. HyQue identified 24 novel but well-supported candidate aging-related genes for further experimental validation. Conclusions We use semantic technologies to discover candidate aging genes whose effects on lifespan are not yet well understood. Our customized HyQue system, the aging research knowledge base it operates over, and HyQue evaluations of all C. elegans genes are freely available at http://hyque.semanticscience.org .
Jet fuel exposure and auditory outcomes in Australian air force personnel

Abstract Background Animal data suggest that jet fuels such as JP-8 are associated with hearing deficits when combined with noise and that the effect is more pronounced than with noise exposure alone. Some studies suggest peripheral dysfunction while others suggest central auditory dysfunction. Human data are limited in this regard. The aim of this study was to investigate the possible chronic adverse effects of JP-8 combined with noise exposure on the peripheral and central auditory systems in humans. Methods Fifty-seven participants who were current personnel from the Royal Australian Air Force were selected. Based on their levels of exposure to jet fuels, participants were divided into three exposure groups (low, moderate, high). Groups were also categorised based on their noise exposure levels (low, moderate, high). All participants were evaluated by tympanometry, pure-tone audiometry (1–12 kHz), distortion product otoacoustic emissions (DPOAEs), auditory brainstem response (ABR), words-in-noise, compressed speech, dichotic digit test, pitch pattern sequence test, duration pattern sequence test and adaptive test of temporal resolution. All auditory tests were carried out after the participants were away from the Air Force base for a minimum of two weeks, thus two weeks without jet fuel and noise exposure. Results Jet fuel exposure was significantly associated with hearing thresholds at 4 and 8 kHz; average hearing thresholds across frequencies in the better ear; DPOAEs at 2.8, 4 and 6 kHz; ABR wave V latency in the right ear; compressed speech and words-in-noise. Further analyses revealed that participants with low exposure level to jet fuels showed significantly better results for the aforementioned procedures than participants with moderate and high exposure levels. All results were controlled for the covariates of age and noise exposure levels. Conclusions The results suggest that jet fuel exposure, when combined with noise exposure, has an adverse effect on audibility in humans. Taking all the test results into consideration, jet fuel exposure combined with noise exposure specifically seems to affect the peripheral hearing system in humans.
An integrated genetic, genomic and systems approach defines gene networks regulated by the interaction of light and carbon signaling pathways in Arabidopsis

Abstract Background Light and carbon are two important interacting signals affecting plant growth and development. The mechanism(s) and/or genes involved in sensing and/or mediating the signaling pathways involving these interactions are unknown. This study integrates genetic, genomic and systems approaches to identify a genetically perturbed gene network that is regulated by the interaction of carbon and light signaling in Arabidopsis. Results C arbon and l ight i nsensitive (cli) mutants were isolated. Microarray data from cli186 is analyzed to identify the genes, biological processes and gene networks affected by the integration of light and carbon pathways. Analysis of this data reveals 966 genes regulated by light and/or carbon signaling in wild-type. In cli186, 216 of these light/carbon regulated genes are misregulated in response to light and/or carbon treatments where 78% are misregulated in response to light and carbon interactions. Analysis of the gene lists show that genes in the biological processes "energy" and "metabolism" are over-represented among the 966 genes regulated by carbon and/or light in wild-type, and the 216 misregulated genes in cli186. To understand connections among carbon and/or light regulated genes in wild-type and the misregulated genes in cli186, the microarray data is interpreted in the context of metabolic and regulatory networks. The network created from the 966 light/carbon regulated genes in wild-type, reveals that cli186 is affected in the light and/or carbon regulation of a network of 60 connected genes, including six transcription factors. One transcription factor, HAT22 appears to be a regulatory "hub" in the cli186 network as it shows regulatory connections linking a metabolic network of genes involved in "amino acid metabolism", "C-compound/carbohydrate metabolism" and "glycolysis/gluconeogenesis". Conclusion The global misregulation of gene networks controlled by light and carbon signaling in cli186 indicates that it represents one of the first Arabidopsis mutants isolated that is specifically disrupted in the integration of both carbon and light signals to control the regulation of metabolic, developmental and regulatory genes. The network analysis of misregulated genes suggests that CLI186 acts to integrate light and carbon signaling interactions and is a master regulator connecting the regulation of a host of downstream metabolic and regulatory processes.
Diagnostic performance of image navigated coronary CMR angiography in patients with coronary artery disease

Abstract Background The use of coronary MR angiography (CMRA) in patients with coronary artery disease (CAD) remains limited due to the long scan times, unpredictable and often non-diagnostic image quality secondary to respiratory motion artifacts. The purpose of this study was to evaluate CMRA with image-based respiratory navigation (iNAV CMRA) and compare it to gold standard invasive x-ray coronary angiography in patients with CAD. Methods Consecutive patients referred for CMR assessment were included to undergo iNAV CMRA on a 1.5 T scanner. Coronary vessel sharpness and a visual score were assigned to the coronary arteries. A diagnostic reading was performed on the iNAV CMRA data, where a lumen narrowing >50% was considered diseased. This was compared to invasive x-ray findings. Results Image-navigated CMRA was performed in 31 patients (77% male, 56 ± 14 years). The iNAV CMRA scan time was 7 min:21 s ± 0 min:28 s. Out of a possible 279 coronary segments, 26 segments were excluded from analysis due to stents or diameter less than 1.5 mm, resulting in a total of 253 coronary segments. Diagnostic image quality was obtained for 98% of proximal coronary segments, 94% of middle segments, and 91% of distal coronary segments. The sensitivity and specificity was 86% and 83% per patient, 80% and 92% per vessel and 73% and 95% per segment. Conclusion In this study, iNAV CMRA offered a very good diagnostic performance when compared against invasive x-ray angiography. Due to the short and predictable scan time it can add clinical value as a part of a comprehensive CAD assessment protocol.
Landscape genomics: natural selection drives the evolution of mitogenome in penguins

Abstract Background Mitochondria play a key role in the balance of energy and heat production, and therefore the mitochondrial genome is under natural selection by environmental temperature and food availability, since starvation can generate more efficient coupling of energy production. However, selection over mitochondrial DNA (mtDNA) genes has usually been evaluated at the population level. We sequenced by NGS 12 mitogenomes and with four published genomes, assessed genetic variation in ten penguin species distributed from the equator to Antarctica. Signatures of selection of 13 mitochondrial protein-coding genes were evaluated by comparing among species within and among genera (Spheniscus, Pygoscelis, Eudyptula, Eudyptes and Aptenodytes). The genetic data were correlated with environmental data obtained through remote sensing (sea surface temperature [SST], chlorophyll levels [Chl] and a combination of SST and Chl [COM]) through the distribution of these species. Results We identified the complete mtDNA genomes of several penguin species, including ND6 and 8 tRNAs on the light strand and 12 protein coding genes, 14 tRNAs and two rRNAs positioned on the heavy strand. The highest diversity was found in NADH dehydrogenase genes and the lowest in COX genes. The lowest evolutionary divergence among species was between Humboldt (Spheniscus humboldti) and Galapagos (S. mendiculus) penguins (0.004), while the highest was observed between little penguin (Eudyptula minor) and Adélie penguin (Pygoscelis adeliae) (0.097). We identified a signature of purifying selection (Ka/Ks < 1) across the mitochondrial genome, which is consistent with the hypothesis that purifying selection is constraining mitogenome evolution to maintain Oxidative phosphorylation (OXPHOS) proteins and functionality. Pairwise species maximum-likelihood analyses of selection at codon sites suggest positive selection has occurred on ATP8 (Fixed-Effects Likelihood, FEL) and ND4 (Single Likelihood Ancestral Counting, SLAC) in all penguins. In contrast, COX1 had a signature of strong negative selection. ND4 Ka/Ks ratios were highly correlated with SST (Mantel, p-value: 0.0001; GLM, p-value: 0.00001) and thus may be related to climate adaptation throughout penguin speciation. Conclusions These results identify mtDNA candidate genes under selection which could be involved in broad-scale adaptations of penguins to their environment. Such knowledge may be particularly useful for developing predictive models of how these species may respond to severe climatic changes in the future.
Latin American Study of Nutrition and Health (ELANS): rationale and study design

Abstract Background Obesity is growing at an alarming rate in Latin America. Lifestyle behaviours such as physical activity and dietary intake have been largely associated with obesity in many countries; however studies that combine nutrition and physical activity assessment in representative samples of Latin American countries are lacking. The aim of this study is to present the design rationale of the Latin American Study of Nutrition and Health/Estudio Latinoamericano de Nutrición y Salud (ELANS) with a particular focus on its quality control procedures and recruitment processes. Methods/Design The ELANS is a multicenter cross-sectional nutrition and health surveillance study of a nationally representative sample of urban populations from eight Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Perú and Venezuela). A standard study protocol was designed to evaluate the nutritional intakes, physical activity levels, and anthropometric measurements of 9000 enrolled participants. The study was based on a complex, multistage sample design and the sample was stratified by gender, age (15 to 65 years old) and socioeconomic level. A small-scale pilot study was performed in each country to test the procedures and tools. Discussion This study will provide valuable information and a unique dataset regarding Latin America that will enable cross-country comparisons of nutritional statuses that focus on energy and macro- and micronutrient intakes, food patterns, and energy expenditure. Trial Registration Clinical Trials NCT02226627