The relationship between nanoscale genome organization and gene expression in mouse embryonic stem cells during pluripotency transition.

During early development, gene expression is tightly regulated. However, how genome organization controls gene expression during the transition from naïve embryonic stem cells to epiblast stem cells is still poorly understood. Using single-molecule microscopy approaches to reach nanoscale resolution, we show that genome remodeling affects gene transcription during pluripotency transition. Specifically, after exit from the naïve pluripotency state, chromatin becomes less compacted, and the OCT4 transcription factor has lower mobility and is more bound to its cognate sites. In epiblast cells, the active transcription hallmark, H3K9ac, decreases within the Oct4 locus, correlating with reduced accessibility of OCT4 and, in turn, with reduced expression of Oct4 nascent RNAs. Despite the high variability in the distances between active pluripotency genes, distances between Nodal and Oct4 decrease during epiblast specification. In particular, highly expressed Oct4 alleles are closer to nuclear speckles during all stages of the pluripotency transition, while only a distinct group of highly expressed Nodal alleles are in close proximity to Oct4 when associated with a nuclear speckle in epiblast cells. Overall, our results provide new insights into the role of the spatiotemporal genome remodeling during mouse pluripotency transition and its correlation with the expression of key pluripotency genes.

Identification of a gene expression signature associated with breast cancer survival and risk that improves clinical genomic platforms.

Motivation: Modern genomic technologies allow us to perform genome-wide analysis to find gene markers associated with the risk and survival in cancer patients. Accurate risk prediction and patient stratification based on robust gene signatures is a key path forward in personalized treatment and precision medicine. Several authors have proposed the identification of gene signatures to assign risk in patients with breast cancer (BRCA), and some of these signatures have been implemented within commercial platforms in the clinic, such as Oncotype and Prosigna. However, these platforms are black boxes in which the influence of selected genes as survival markers is unclear and where the risk scores provided cannot be clearly related to the standard clinicopathological tumor markers obtained by immunohistochemistry (IHC), which guide clinical and therapeutic decisions in breast cancer. Results: Here, we present a framework to discover a robust list of gene expression markers associated with survival that can be biologically interpreted in terms of the three main biomolecular factors (IHC clinical markers: ER, PR and HER2) that define clinical outcome in BRCA. To test and ensure the reproducibility of the results, we compiled and analyzed two independent datasets with a large number of tumor samples (1024 and 879) that include full genome-wide expression profiles and survival data. Using these two cohorts, we obtained a robust subset of gene survival markers that correlate well with the major IHC clinical markers used in breast cancer. The geneset of survival markers that we identify (which includes 34 genes) significantly improves the risk prediction provided by the genesets included in the commercial platforms: Oncotype (16 genes) and Prosigna (50 genes, i.e. PAM50). Furthermore, some of the genes identified have recently been proposed in the literature as new prognostic markers and may deserve more attention in current clinical trials to improve breast cancer risk prediction. Availability and implementation: All data integrated and analyzed in this research will be available on GitHub (https://github.com/jdelasrivas-lab/breastcancersurvsign), including the R scripts and protocols used for the analyses. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Two plus one is almost three: a fast approximation for multi-view deconvolution.

Multi-view deconvolution is a powerful image-processing tool for light sheet fluorescence microscopy, providing isotropic resolution and enhancing the image content. However, performing these calculations on large datasets is computationally demanding and time-consuming even on high-end workstations. Especially in long-time measurements on developing animals, huge amounts of image data are acquired. To keep them manageable, redundancies should be removed right after image acquisition. To this end, we report a fast approximation to three-dimensional multi-view deconvolution, denoted 2D+1D multi-view deconvolution, which is able to keep up with the data flow. It first operates on the two dimensions perpendicular and subsequently on the one parallel to the rotation axis, exploiting the rotational symmetry of the point spread function along the rotation axis. We validated our algorithm and evaluated it quantitatively against two-dimensional and three-dimensional multi-view deconvolution using simulated and real image data. 2D+1D multi-view deconvolution takes similar computation time but performs markedly better than the two-dimensional approximation only. Therefore, it will be most useful for image processing in time-critical applications, where the full 3D multi-view deconvolution cannot keep up with the data flow.

Post-vasectomy semen analysis compliance with use of a home-based test.

INTRODUCTION Although the importance of post-vasectomy semen analysis (PVSA) is well known, compliance with this test has historically been low. We sought to compare compliance with PVSA when using a home-based testing kit with traditional office based microscopy, and to estimate the impact of compliance differences on the risk of undetected vasectomy failure. MATERIALS AND METHODS: A retrospective review of vasectomies performed by three providers was performed. Patients were prescribed either traditional office-based PVSA testing (Group 1) or home-based PVSA testing (Group 2). Compliance with PVSA testing was defined as completion of at least one PVSA test. Decision analysis methodology was applied to estimate the risk of undetected vasectomy failure in each group. RESULTS: A total of 226 vasectomies were reviewed, 141 in Group 1 and 85 in Group 2. The compliance rate was 65.96% in Group 1 compared to 76.47% in Group 2 (p = .095). When utilizing a single home-based test, the estimated risk of undetected vasectomy failure was 3.65% in Group 1 compared to 4.09% in Group 2. When utilizing two serial home-based tests, the estimated risk in Group 2 decreased to 2.87%. CONCLUSION: As home-based PVSA tests become more widely available, it is important to understand their impact. The availability of such tests may lead to improved compliance with PVSA testing. In turn, increased compliance may offer increased detection of vasectomy failure. Further study is needed with regard to the impact of home-based tests.

Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling.

BACKGROUND: Identification of biomarkers associated with the prognosis of different cancer subtypes is critical to achieve better therapeutic assistance. In colorectal cancer (CRC) the discovery of stable and consistent survival markers remains a challenge due to the high heterogeneity of this class of tumors. In this work, we identified a new set of gene markers for CRC associated to prognosis and risk using a large unified cohort of patients with transcriptomic profiles and survival information. RESULTS: We built an integrated dataset with 1273 human colorectal samples, which provides a homogeneous robust framework to analyse genome-wide expression and survival data. Using this dataset we identified two sets of genes that are candidate prognostic markers for CRC in stages III and IV, showing either up-regulation correlated with poor prognosis or up-regulation correlated with good prognosis. The top 10 up-regulated genes found as survival markers of poor prognosis (i.e. low survival) were: DCBLD2, PTPN14, LAMP5, TM4SF1, NPR3, LEMD1, LCA5, CSGALNACT2, SLC2A3 and GADD45B. The stability and robustness of the gene survival markers was assessed by cross-validation, and the best-ranked genes were also validated with two external independent cohorts: one of microarrays with 482 samples; another of RNA-seq with 269 samples. Up-regulation of the top genes was also proved in a comparison with normal colorectal tissue samples. Finally, the set of top 100 genes that showed overexpression correlated with low survival was used to build a CRC risk predictor applying a multivariate Cox proportional hazards regression analysis. This risk predictor yielded an optimal separation of the individual patients of the cohort according to their survival, with a p-value of 8.25e-14 and Hazard Ratio 2.14 (95% CI: 1.75-2.61). CONCLUSIONS: The results presented in this work provide a solid rationale for the prognostic utility of a new set of genes in CRC, demonstrating their potential to predict colorectal tumor progression and evolution towards poor survival stages. Our study does not provide a fixed gene signature for prognosis and risk prediction, but instead proposes a robust set of genes ranked according to their predictive power that can be selected for additional tests with other CRC clinical cohorts.

Antropología filosófica: un aspecto pendiente en la investigación de Enfermería en América Latina / Philosophical Anthropology: An sigue pending in nursing research in Latin America

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Envelope filter sequence to delete blinks and overshoots.

BACKGROUND: Eye movements have been used in control interfaces and as indicators of somnolence, workload and concentration. Different techniques can be used to detect them: we focus on the electrooculogram (EOG) in which two kinds of interference occur: blinks and overshoots. While they both draw bell-shaped waveforms, blinks are caused by the eyelid, whereas overshoots occur due to target localization error and are placed on saccade. They need to be extracted from the EOG to increase processing effectiveness. METHODS: This paper describes off- and online processing implementations based on lower envelope for removing bell-shaped noise; they are compared with a 300-ms-median filter. Techniques were analyzed using two kinds of EOG data: those modeled from our own design, and real signals. Using a model signal allowed to compare filtered outputs with ideal data, so that it was possible to quantify processing precision to remove noise caused by blinks, overshoots, and general interferences. We analyzed the ability to delete blinks and overshoots, and waveform preservation. RESULTS: Our technique had a high capacity for reducing interference amplitudes (>97%), even exceeding median filter (MF) results. However, the MF obtained better waveform preservation, with a smaller dependence on fixation width. CONCLUSIONS: The proposed technique is better at deleting blinks and overshoots than the MF in model and real EOG signals.

Envelopment filter and K-means for the detection of QRS waveforms in electrocardiogram.

The electrocardiogram (ECG) is a well-established technique for determining the electrical activity of the heart and studying its diseases. One of the most common pieces of information that can be read from the ECG is the heart rate (HR) through the detection of its most prominent feature: the QRS complex. This paper describes an offline version and a real-time implementation of a new algorithm to determine QRS localization in the ECG signal based on its envelopment and K-means clustering algorithm. The envelopment is used to obtain a signal with only QRS complexes, deleting P, T, and U waves and baseline wander. Two moving average filters are applied to smooth data. The K-means algorithm classifies data into QRS and non-QRS. The technique is validated using 22 h of ECG data from five Physionet databases. These databases were arbitrarily selected to analyze different morphologies of QRS complexes: three stored data with cardiac pathologies, and two had data with normal heartbeats. The algorithm has a low computational load, with no decision thresholds. Furthermore, it does not require any additional parameter. Sensitivity, positive prediction and accuracy from results are over 99.7%.

EEG feature variations under stress situations.

The goal of this study is to identify EEG parameters and electrode positions with the highest significant values to differentiate between tasks and relax periods. Different signals were recorded as 12 subjects are doing arithmetic and memory tasks under stress condition. The test consisted of an initial and final 5-minute relax periods and three 4-minute performance phases with increased stress level. θ and α bands concentrated mainly features whose variation were significant, and F3 and P4 were the best positions to distinguish between performed tasks and arousal level.

Chen's attractor exists if Lorenz repulsor exists: the Chen system is a special case of the Lorenz system.

In this paper, we show, by means of a linear scaling in time and coordinates, that the Chen system, given by x=a(y-x), y=(c-a)x+cy-xz, z=-bz+xy, is, generically (c≠0), a special case of the Lorenz system. First, we infer that it is enough to consider two parameters to study its dynamics. Furthermore, we prove that there exists a homothetic transformation between the Chen and the Lorenz systems and, accordingly, all the dynamical behavior exhibited by the Chen system is present in the Lorenz system (since the former is a special case of the second). We illustrate our results relating Hopf bifurcations, periodic orbits, invariant surfaces, and chaotic attractors of both systems. Since there has been a large literature that has ignored this equivalence, the aim of this paper is to review and clarify this field. Unfortunately, a lot of the previous papers on the Chen system are unnecessary or incorrect.

Comment on "Sil'nikov chaos of the Liu system" [Chaos 18, 013113 (2008)].

In the referenced paper, the authors use the undetermined coefficient method to prove analytically the existence of homoclinic and heteroclinic orbits in a Lorenz-like system. If the proof was correct, the existence of horseshoe chaos would be guaranteed via the Sil'nikov criterion. However, we hereby show that their demonstration is incorrect for two reasons. On the one hand, they wrongly use a symmetry the Lorenz-like system exhibits. On the other hand, they try to find structurally unstable global bifurcations by means of a series that is uniformly convergent in an open set of the parameter space: this would imply that the dynamical object they have found is structurally stable.

κ-NN for the classification of human cancer samples using the gene expression profiles.

The [Formula: see text]-Nearest Neighbor (k-NN) classifier has been applied to the identification of cancer samples using the gene expression profiles with encouraging results. However, the performance of [Formula: see text]-NN depends strongly on the distance considered to evaluate the sample proximities. Besides, the choice of a good dissimilarity is a difficult task and depends on the problem at hand. In this chapter, we introduce a method to learn the metric from the data to improve the [Formula: see text]-NN classifier. To this aim, we consider a regularized version of the kernel alignment algorithm that incorporates a term that penalizes the complexity of the family of distances avoiding overfitting. The error function is optimized using a semidefinite programming approach (SDP). The method proposed has been applied to the challenging problem of cancer identification using the gene expression profiles. Kernel alignment [Formula: see text]-NN outperforms other metric learning strategies and improves the classical [Formula: see text]-NN algorithm.

Combining dissimilarities in a Hyper Reproducing Kernel Hilbert Space for complex human cancer prediction.

DNA microarrays provide rich profiles that are used in cancer prediction considering the gene expression levels across a collection of related samples. Support Vector Machines (SVM) have been applied to the classification of cancer samples with encouraging results. However, they rely on Euclidean distances that fail to reflect accurately the proximities among sample profiles. Then, non-Euclidean dissimilarities provide additional information that should be considered to reduce the misclassification errors. In this paper, we incorporate in the nu-SVM algorithm a linear combination of non-Euclidean dissimilarities. The weights of the combination are learnt in a (Hyper Reproducing Kernel Hilbert Space) HRKHS using a Semidefinite Programming algorithm. This approach allows us to incorporate a smoothing term that penalizes the complexity of the family of distances and avoids overfitting. The experimental results suggest that the method proposed helps to reduce the misclassification errors in several human cancer problems.

Frecuencia y complicaciones materno perinatales de la malaria gestacional por Plasmodium Falciparum Hospital de apoyo Jese Alfredo Mendoza Olavaria. Tumbes / Frequency and maternal perinatal complications of gestational malaria, by Plasmodium Falciparum Hospital de apoyo Jese Alfredo Mendoza Olavaria. Tumbes

Investigación realizada en gestantes atendidas en el Hospital "José Alfredo Mendoza Olavaria" de Tumbes entre enero de 1998 a junio de 1999.El universo fue de 2670 gestantes y la muestra la constituyeron 73 pacientes con malaria a P. Falciparum. Se determinó que de 2670 gestantes atendidas 90 tuvieron malaria (3.37 por ciento), de los cuales 17 (0.64 por ciento) fueron por P. Vivax y en 73 (2.73 por ciento)el agente fue P. Falciparum. Del total de casos por P. Falciparum casi la mitad procedían de la zona rural (47.95 por ciento) y el grupo de edad más frecuente fue el de 20 a 24 años (41.09 por ciento), las multigestas estuvieron en mayor porcentaje (68.49 por ciento), siendo los dos últimos trimestres las etapas de mayor infección (86.31 por ciento. Por parte de la madre, la fiebre, la cefalea y las molestias gástricas fueron los motivos de consulta mas frecuentes: 57, 46 y35 por ciento respectivamente y la anemia, la hipoglisemia y la amenaza de parto prematuro (44, 36 Y 27 respectivamente) las complicaciones más frecuentes, habiendo fallecido 3 pacientes (4.11 por ciento). En el producto de la gestación las complicaciones perinatales más frecuentes fueron el peso bajo al nacer (27.40 por ciento) y el sufrimiento fetal agudo (21.92 por ciento). En un caso se hizo el diagnostico de malaria congénita (1.37 por ciento) y hubieron 3 muertes fetales (4.11 por ciento).

Investigation carried out in pregnancy assisted in the Hospital Jose Alfredo Mendoza Olavaria gives you knock down among January she gives 1998 to June she gives 1999. The universe was gives 2670 pregnancies and the sample 73 patients they constituted in with malaria to P. Falciparum. You determines that she gives 2670 attended pregnancies 90 they had malaria (3.37 per cent), give those which 17 (0.64 per cent) theywere for Vivacious P. and in 73 (2.73 per cent) the agent was P. Falciparum.Give the total she gives case for P. Falciparum almost the half proceeded she gives the rural area (47.95 per cent), and the group gives age but it frequents the one she went she gives 20 to 24 years (41.09 per cent), the multigestas was in more percentage (68.49 per cent), being the last two trimesters the stages gives bigger infection (86.31 per cent). On the part of the mother , the fever, the migraine and the gastric misances were the reasons she gives consultation but you frequent: 57,46 and 35 per cent respectively and the anemia, the hypoglycemia and the threat gives chilbirth premature( 44,36 and 27 respectively) the complications but you frequent, having died 3 patients (4.11 per cent). In the product she gives the gestation the perinatal complications more frequent they went the low weight when being born (27.40 per cent) and the sharp fetal suffering (21.92 per cent) . In a case it was made the I diagnose she gives congenital malaria (1.37 per cent) and they had 3 deaths fetales (4.11 per cent).

Abdomen agudo quirúrgico en el anciano

Las principales causas de abdomen agudo que hemos visto en este estudio que son la obstrucción intestinal y la patología de las vías bibliares, podrían ser significativamente variadas, si las trataremos de inicio en forma electiva, una vez diagnosticadas. Otro punto a resaltar, en este estudio, es alta frecuencia de cuadros complicados, por falta de un dignostico precoz, esto podria ser atribuible a que los pacientes llegan en forma tardia a buscar atención médica por diversos problemas sociales propios de este grupo humano, y/o por falta de acuciocidad en el diagnóstico clínico al no encontrarse en ellos la signología clásica. Para finalizar no debemos de olvidar que en el anciano la morbilidad perioperatoria está aumentando por los cambios fisiológicos propios de esta edad, que no son capaces de compensar con facilidad las agreciones que sufre su organismo y que además un buen porcentaje de ellos vienen con una patología de fondo asociada. Debemos preocuparnos con mucho celo de la compensación peoperatoria en el menor tiempo permisible para una cirugía adecuada así como enel cuidado postoperatorio que tiene que estar orientado a la rápidad recuperación del pacientes a fin de evitar la complicaciones de una postración prolongada.