bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-Sensitive Mutation Detection and Genome-Wide DNA Copy Number Reconstruction by Error-Corrected Circulating Tumor DNA Sequencing
Authors: Mansukhani Sonia , Barber Louise J , Kleftogiannis Dimitrios , Moorcraft Sing Yu , Davidson Michael , Woolston Andrew , Proszek Paula Zuzanna , Griffiths Beatrice , Fenwick Kerry , Herman Bram , Matthews Nik , O'Leary Ben , Hulkki Sanna , Gonzalez De Castro David , Patel Anisha , Wotherspoon Andrew , Okachi Aleruchi , Rana Isma , Begum Ruwaida , Davies Matthew N , Powles Thomas , von Loga Katharina , Hubank Michael , Turner Nick , Watkins David , Chau Ian , Cunningham David , Lise Stefano , Starling Naureen , Gerlinger Marco 
Published: August 2018

Abstract

BACKGROUND
Circulating free DNA sequencing (cfDNA-Seq) can portray cancer genome landscapes, but highly sensitive and specific technologies are necessary to accurately detect mutations with often low variant frequencies.

METHODS
We developed a customizable hybrid-capture cfDNA-Seq technology using off-the-shelf molecular barcodes and a novel duplex DNA molecule identification tool for enhanced error correction.

RESULTS
Modeling based on cfDNA yields from 58 patients showed that this technology, requiring 25 ng of cfDNA, could be applied to &gt;95% of patients with metastatic colorectal cancer (mCRC). cfDNA-Seq of a 32-gene, 163.3-kbp target region detected 100% of single-nucleotide variants, with 0.15% variant frequency in spike-in experiments. Molecular barcode error correction reduced false-positive mutation calls by 97.5%. In 28 consecutively analyzed patients with mCRC, 80 out of 91 mutations previously detected by tumor tissue sequencing were called in the cfDNA. Call rates were similar for point mutations and indels. cfDNA-Seq identified typical mCRC driver mutations in patients in whom biopsy sequencing had failed or did not include key mCRC driver genes. Mutations only called in cfDNA but undetectable in matched biopsies included a subclonal resistance driver mutation to anti-EGFR antibodies in KRAS, parallel evolution of multiple PIK3CA mutations in 2 cases, and TP53 mutations originating from clonal hematopoiesis. Furthermore, cfDNA-Seq off-target read analysis allowed simultaneous genome-wide copy number profile reconstruction in 20 of 28 cases. Copy number profiles were validated by low-coverage whole-genome sequencing.

CONCLUSIONS
This error-corrected, ultradeep cfDNA-Seq technology with a customizable target region and publicly available bioinformatics tools enables broad insights into cancer genomes and evolution.

ClinicalTrials.gov Identifier
NCT02112357
Los límites de la democracia argentina. Lecturas desde el proyecto de ley de defensa de la democracia de 1961
Authors: Azzolini Nicolás 
Published: August 2018

En este artículo trabajamos con los debates que se dieron con relación al proyecto de ley de defensa de la democracia que fue presentado en el Congreso de la Nación en 1961. Pese a que el proyecto buscaba defender a la democracia contra el avance del comunismo y otros tipos de extremismos, dichos debates nos permiten reconstruir los distintitos sentidos ligados al concepto de democracia, las diferencias entre distintos sectores antiperonistas y los límites de un lenguaje político basado en la defensa de la democracia. Para ello, desde una metodología cualitativa, se analizan fuentes primarias.
“Remembering with advantages”: The memory of the Great War in Australia
Authors: Holbrook Carolyn 
Published: August 2018

La memoria australiana de la Gran Guerra siempre se ha expresado de modo más efusivo en los ritos del día de Anzac: un acontecimiento que reconoce el aniversario de participación en la primera batalla en la Guerra de los australianos en Turquía, el 25 de abril de 1915. En las décadas tras los años 1914-1918, los efectos devastadores de la Guerra se apaciguaron en parte gracias al orgullo que los australianos sentían en la reputación de sus soldados como combatientes. En la década de 1960 los ritos de Anzac estaban en un declive palpable. Los australianos jóvenes eran reacios a los valores de la generación de la Gran Guerra y creían que las prácticas conmemorativas del día de Anzac glorificaban la Guerra. A pesar de la creencia generalizada de que el día de Anzac moriría junto al último de los veteranos, este ha resurgido de modo notable. Este hecho se puede explicar por la reconstrucción de la leyenda de Anzac, que ha evolucionado desde el mito anclado en el patriotismo racial británico y el nacionalismo marcial hacia uno que habla en el idioma moderno del trauma, el sufrimiento y la empatía. Lo que permanece de la leyenda original de Anzac es la creencia sostenida de modo global por los australianos contemporáneos de que su conciencia nacional nació en Gallipoli, el 25 de abril de 1915.
New Algorithms for δγ-Order Preserving Matching
Authors: Mendivelso Juan , Niquefa Rafael , Pinzón Yoan , Hernández Germán 
Published: August 2018

Context: Order-preserving matching regards the relative order of strings. However, its application areas require more flexibility in the matching paradigm. We advance in this direction in this paper that extends our previous work [27].Method: We define γ -order preserving matching as an approximate variant of order-preserving matching. We devise two solutions for it based on segment and Fenwick trees: segtreeBA and bitBA.Results: We experimentally show the efficiency of our algorithms compared to the ones presented in [26] (naiveA and updateBA). Also, we present applications of our approach in music retrieval and stock market analysis.Conclusions: Even though the worst-case time complexity of the proposed algorithms (namely, O(nm log m)) is higher than the Ѳ(nm)-time complexity of updateBA, their Ω (n log n) lower bound makes them more efficient in practice. On the other hand, we show that our approach is useful to identify similarity in music melodies and stock price trends through real application examples.
Explorando o conceito "Densidade" com estudantes do ensino fundamental
Authors: Dias Broietti Fabiele Cristiane , Ferracin Talita Parpinelli , Arrigo Viviane 
Published: August 2018

La densidad es un concepto científico que genera algunas confusiones entre los estudiantes, siendo muchas veces enseñado solamente desde el modelo matemático, esto acarrea grandes dificultades para comprenderlo en situaciones cotidianas. En este contexto, presentamos resultados de investigación sobre la manera como estudiantes de noveno grado de la educación básica comprenden este concepto. También presentamos y discutimos una secuencia de actividades, elaborada con base en la estrategia metodológica de los tres momentos pedagógicos, aplicada con este grupo de estudiantes. Los datos fueron tomados por medio de cuestionarios propuestos en el primero y tercer momento, además de los registros de campo a lo largo del desarrollo de las actividades. El análisis y la interpretación de los datos se realizó con base en los presupuestos del análisis de contenido. Como resultado encontramos que la mayoría de los estudiantes relaciona la flotación de los cuerpos con la densidad, sin embargo, presentan otros argumentos considerando otros parámetros como peso, cantidad y la no miscibilidad. En este sentido, resaltamos la necesidad de estudios que amplíen esta discusión así como de otras propuestas de enseñanza que discutan este concepto en los diferentes niveles de enseñanza.
Ekskluzywizm ewangelikalny
Authors: Kubacki Zbigniew 
Published: August 2018

Within the Christian theology of religions one distinguishes three basic paradigms: exclusivism, inclusivism and pluralism. Pluralism considers all religions as equal ways of salvation leading to God. It denies that Jesus Christ is the unique Savior of the world. Inclusivism maintains the unicity and salvivic universality of Jesus Christ, but affirms that explicit faith in Jesus Christ is not necessary for salvation for unevangelized people. Exclusivism is the view that Jesus Christ is the only Savior of the world and that one must believe God’s special revelation that culminates in the gospel of Christ in order to be saved. Evangelical theologians principally maintain this position. Interestingly enough, on the one hand they affirm that children who die in infancy (as well as people who are mentally incompetent) are included within the circle of God’s saving grace and will be saved; on the other hand, they say that since the first coming of Christ the only way of salvation is explicit faith in him.The article is divided into three parts. The first part examines the argument of those theologians about the fate of children who die in infancy and then compares it with the teaching of the Catholic Church expressed by the International Theological Commission in its document The Hope of Salvation for Infants Who Die Without Being Baptized (2007). The second part examines the biblical and theological arguments advanced by evangelical theologians in favor of exclusivism. In the third part these arguments are discussed from the perspective of Catholic theology. For Catholics as much as for evangelicals, there is no doubt that Jesus Christ is the unique Savior of the world and that salvation has always been by grace through faith. The difference concerns the content of this saving faith. Must it have as its object an explicit knowledge of Jesus Christ, as is argued by the evangelical exclusivists?
Spike-Conducting Integrate-and-Fire Model
Authors: Ashida Go , Nogueira Waldo 
Published: August 2018

AbstractModeling is a useful tool for investigating various biophysical characteristics of neurons. Recent simulation studies of propagating action potentials (spike conduction) along axons include the investigation of neuronal activity evoked by electrical stimulation from implantable prosthetic devices. In contrast to point-neuron simulations, where a large variety of models are readily available, Hodgkin–Huxley-type conductance-based models have been almost the only option for simulating axonal spike conduction, as simpler models cannot faithfully replicate the waveforms of propagating spikes. Since the amount of available physiological data, especially in humans, is usually limited, calibration, and justification of the large number of parameters of a complex model is generally difficult. In addition, not all simulation studies of axons require detailed descriptions of nonlinear ionic dynamics. In this study, we construct a simple model of spike generation and conduction based on the exponential integrate-and-fire model, which can simulate the rapid growth of the membrane potential at spike initiation. In terms of the number of parameters and equations, this model is much more compact than conventional models, but can still reliably simulate spike conduction along myelinated and unmyelinated axons that are stimulated intracellularly or extracellularly. Our simulations of auditory nerve fibers with this new model suggest that, because of the difference in intrinsic membrane properties, the axonal spike conduction of high-frequency nerve fibers is faster than that of low-frequency fibers. The simple model developed in this study can serve as a computationally efficient alternative to more complex models for future studies, including simulations of neuroprosthetic devices.
A Brain–Heart Biomarker for Epileptogenesis
Authors: Bahari Fatemeh , Ssentongo Paddy , Schiff Steven J. , Gluckman Bruce J. 
Published: August 2018

Postinjury epilepsy is an potentially preventable sequela in as many as 20% of patients with brain insults. For these cases biomarkers of epileptogenesis are critical to facilitate identification of patients at high-risk of developing epilepsy and to introduce effective anti-epileptogenic interventions. Here, we demonstrate that delayed brain–heart coincidences serve as a reliable biomarker. In a murine model of post-infection acquired epilepsy, we used long-term simultaneous measurements of the brain activity via electroencephalography and autonomic cardiac activity via electrocardiography, in male mice, to quantitatively track brain–heart interactions during epileptogenesis. We find that abnormal cortical discharges precede abnormal fluctuations in the cardiac rhythm at the resolution of single beat-to-beat intervals. The delayed brain–heart coincidence is detectable as early as the onset of chronic measurements, 2–14 weeks before the first seizure, only in animals that become epileptic, and increases during epileptogenesis. Therefore, delayed brain–heart coincidence serves as a biomarker of epileptogenesis and could be used for phenotyping, diagnostic, and therapeutic purposes.SIGNIFICANCE STATEMENTNo biomarker that readily predicts and tracks epileptogenesis currently exists for the wide range of human acquired epilepsies. Here, we used long-term measurements of brain and heart activity in a mouse model of post-infection acquired epilepsy to investigate the potential of brain–heart interaction as a biomarker of epileptogenesis. We found that delayed coincidences from brain to heart can clearly separate the mice that became epileptic from those that did not weeks before development of epilepsy. Our findings allow for phenotyping and tracking of epileptogenesis in this and likely other models of acquired epilepsy. Such capability is critical for efficient adjunctive treatment development and for tracking the efficacy of such treatments.
Thalamus Controls Development and Expression of Arousal States in Visual Cortex
Authors: Murata Yasunobu , Colonnese Matthew T. 
Published: August 2018

Two major checkpoints of development in cerebral cortex are the acquisition of continuous spontaneous activity and the modulation of this activity by behavioral state. Despite the critical importance of these functions, the circuit mechanisms of their development remain unknown. Here we use the rodent visual system as a model to test the hypothesis that the locus of circuit change responsible for the developmental acquisition of continuity and state dependence measured in sensory cortex is relay thalamus, rather than the local cortical circuitry or the interconnectivity of the two structures. We conducted simultaneous recordings in the dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (VC) of awake, head-fixed male and female rats using linear multielectrode arrays throughout early development. We find that activity in dLGN becomes continuous and positively correlated with movement (a measure of state dependence) on P13, the same day as VC, and that these properties are not dependent on VC activity. By contrast, silencing dLGN after P13 causes activity in VC to become discontinuous and movement to suppress, rather than augment, cortical firing, effectively reversing development. Thalamic bursting, a core characteristic of non-aroused states, emerged later, on P16, suggesting these processes are developmentally independent. Together our results indicate that cellular or circuit changes in relay thalamus are critical drivers for the maturation of background activity, which occurs around term in humans.SIGNIFICANCE STATEMENTThe developing brain acquires two crucial features, continuous spontaneous activity and its modulation by arousal state, around term in humans and before the onset of sensory experience in rodents. This developmental transition in cortical activity, as measured by electroencephalogram (EEG), is an important milestone for normal brain development and indicates a good prognosis for babies born preterm and/or suffering brain damage such as hypoxic-ischemic encephalopathy. By using the awake rodent visual system as a model, we identify changes occurring at the level of relay thalamus, the major input to cortex, as the critical driver of EEG maturation. These results could help understand the circuit basis of human EEG development to improve diagnosis and treatment of infants in vulnerable situations.
Mental health of working-age populations in Japan who provide nursing care for a person at home: A cross-sectional analysis
Authors: Eguchi Hisashi , Wada Koji 
Published: August 2018

Abstract

Objectives
This study investigated potential associations between having a person in need of nursing care at home and psychological distress amongst the Japanese working population, using a nationally representative sample.

Methods
We extracted data from the 2013 Comprehensive Survey of Living Conditions conducted by the Ministry of Health, Labour and Welfare of Japan. The original survey was conducted amongst 295,367 households in 5,530 randomly selected municipalities. We analyzed participants aged 25-65 years who headed a household. The original questionnaire included questions about the specific qualifications required to receive long-term care insurance benefits, about psychological distress (measured using the K6 scale), and other covariates. If a family contained a member in need of nursing care at home, the person who headed that household was recognized as the participant who had a person in need of nursing care at home. Multiple logistic regression analysis was conducted to investigate the association between having a person in need of nursing care at home and psychological distress.

Results
A total of 36,193 men and 2,765 women were included in the analysis, 2.9% of whom had a person in need of nursing care at home. Statistical analysis revealed an association between having a care-requiring older relative at home and psychological distress (odds ratio: 1.40, 95% confidence interval: 1.01-1.93).

Conclusions
Having a person in need of nursing care at home appears to be positively correlated with worsening mental health of working populations in Japan.
ANTIHYPERTENSIVE THERAPY TACTICS IN HYPERTENSIVE CRISE COMPLICATED BY HAEMORRHAGIC STROKE
Authors: Gendlin G. E. , Melekhov A. V. , Ostrovskaya Yu. I. , Storozhakov G. I. , Gorshkov K. M. , Sokolan D. B. , Aliev I. S. , Voropaeva I. A. 
Published: August 2018

Aim. To identify the optimal tactics of antihypertensive therapy (AHT) in patients with hypertensive crise (HC), complicated by haemorrhagic stroke (HS).Material and methods. Forty patients aged 46–87 years, who were hospitalised with HC and HS as its complication.Results. All patients were divided into two groups, according to the median levels of systolic blood pressure (SBP) at 20 minutes after the start of the treatment: SBP >161 mm Hg vs. SBP <161 mm Hg. A significantly better survival was observed in patients with a higher degree of the 20-minute SBP eduction. In addition, patients were divided into tertiles of the 20-minute SBP levels. Participants with SBP 136–149 mm Hg demonstrated a significantly better survival. The degree of SBP reduction at 220 minutes was not significantly associated with survival. Furthermore, the patients were divided into two groups by the rate of SBP reduction. Faster rates were associated with a better survival (PGW=0,002). The second part of the study was focused on the assessment of effectiveness and safety of urapidil hydrochloride (Ebrantil). The patients were randomised into two groups: one group was administered Ebrantil, while another received the standard neuroresuscitation unit treatment. Ebrantil therapy demonstrated a fast and effective SBP reduction at 20 minutes, which was also associated with a better survival.Conclusion. We identified optimal, associated with a better survival, BP levels (136–149 mm Hg) for patients with HC complicated by HS. Target BP levels should be achieved within 20 minutes, as a slower BP reduction is linked to a worse prognosis. Ebrantil is an effective and safe antihypertensive medication.
ATORVASTATIN IN PRIMARY PREVENTION AMONG MEN WITH HIGH CORONARY RISK LEVELS
Authors: Osipova I. V. , Pyrikova N. V. , Antropova O. N. , Zaltsman A. G. , Miroshnichenko A. I. , Kurbatova I. I. 
Published: August 2018

Aim.To assess the effectiveness of a complex programme of primary cardiovascular prevention, including statin therapy (Liptonorm), among men from an occupational sample who have high coronary risk levels.Material and methods.The occupational sample included male train drivers and train driver assistants, aged 40–55 yeas. The primary prevention programme included the assessment of the risk factors (RFs) and SCORE risk levels; the development of an individual prevention plan; the Workplace Health School, with Self-Control Diary distribution; and the 6-month administration of Liptonorm (mean dose 14,7±5,1 mg/d) in the high-risk group.Results.In 2010–2011, 224 men participated in the primary prevention programme. The high-risk group, as assessed by the SCORE scale, comprised 14,3%. The results of preventive measures, including the 6-month Liptonorm therapy, are presented for the high-risk group. In particular, 29,4% of the men stopped smoking. The daily number of cigarettes smoked at workplace decreased by 5,1. Consumption of >2 drinks per day, overweight, and abdominal obesity prevalence decreased by 12,5%. The prevalence of insufficient rest time and night sleep <7 hours decreased by 28,1%. Fifty per cent of men increased their physical activity levels, while 34,4% increased their consumption of vegetables. Mean levels of blood pressure reduced by 5 mm Hg. Liptonorm therapy was associated with the achievement of target levels of low-density lipoprotein (LDL) cholesterol (in 84,4%) and the reduction in the levels of triglycerides (by 0,2 mmol/l), total cholesterol (by 1,3 mmol/l), and LDL cholesterol (by 0,7 mmol/l). As a result, the levels of total cardiovascular risk decreased by 1,7%. Therefore, at baseline, out of 224 men, 14,3% had high SCORE levels; after the preventive intervention, this proportion was only 3,6%, as 10,7% moved into the category of moderate SCORE risk.Conclusion.The workplace administration of the complex preventive programme, including statin administration, facilitates modification of behavioural RFs, achievement of target blood lipid levels, and total coronary risk reduction.
NON-SPECIFIC CONGENITAL CONNECTIVE TISSUE DISORDERS AS AN INDEPENDENT PREDICTOR OF STRUCTURAL AND FUNCTIONAL ARTERIAL CHANGES
Authors: Semenkin A. A. , Drokina O. V. , Nechaeva G. I. , Zhivilova L. A. , Zhenatov A. B. 
Published: August 2018

Aim. To assess the impact of non-specific congenital connective tissue disorders (CCTD) on the changes in arterial stiffness and endothelial function; to study the role of CCTD as an independent predictor of structural and functional arterial changes.Material and methods. The study included 147 18–50-year-old men and women with CCTD and 85 healthy volunteers, comparable by age and gender (controls). All participants underwent a screening assessment of cardiovascular risk factors (RFs) and the assessment of heart rate variability (HRV), pulse wave velocity (PWV) at baseline (PWVbas) and after sublingual administration of nitroglycerin (PWVntg), and endothelium-dependent vasodilatation (EDVD), assessed by photopletismography.Results. Compared to the control group, CCTD patients had lower values of body mass index (p<0,001), waist circumference, WC (p<0,001), hip circumference, HC (p<0,001), WC/HC ratio (p<0,005), systolic blood pressure (p<0,05), total cholesterol (p<0,001), low-density lipoprotein cholesterol (p<0,005), atherogenicity index (p<0,05), and triglycerides (p<0,005). Moreover, CCTD patients were characterized by sympathetic activation, increased PWVbas (p<0,001), PWVntg (p<0,05), and EDVD (p<0,001). According to the results of stepwise multivariate analyses of the whole sample data, CCTD was a significant independent predictor of PWVbas (p<0,001), PWVntg (p<0,005), and EDVD (p<0,005 and <0,05 in men and women, respectively).Conclusion. Patients with CCTD demonstrated increased arterial stiffness and endothelium-dependent vasodilatation, compared to healthy controls. Independently from cardiovascular RFs and autonomic dysregulation, CCTD is a significant predictor of structural and functional arterial changes and can also have a prognostic value. These findings should be taken into account in the studies which assess vascular parameters.