Miracle-dz/UniFAR-FTUs huggingface dataset:
ERCC5 promoter polymorphisms at –763 and +25 predict the response to oxaliplatin-based chemotherapy in patients with advanced colorectal cancer

2 This study aimed to investigate whether single nucleotide polymorphisms (SNPs) in the promoter of the excision repair cross complementation group 5 (ERCC5) gene influences response to oxaliplatin-based chemotherapy. Eighty-three patients with cytologically or histologically confirmed advanced colorectal cancer (CRC), at least one measurable lesion and underwent oxaliplatin-based chemotherapy were studied. To this end, six polymorphisms (-1415C>T, -763A>G, -413C>T, +25A>G, +202C>T, +372C>T) in the ERCC5 promoter were selected for investigation. Genomic DNA was obtained from peripheral blood cells, and polymerase chain reaction-ligation detection reaction was used to analyze these SNPs. The χ2 test or Fisher’s exact test was then used to investigate the association between polymorphisms and chemotherapy response. Our results showed that the response rate among patients with the -763GG genotype (72.7%) was significantly higher than that of other genotypes (22.2% for AA genotype, P=0.008 and 37.2% for AG genotype, P=0.046 respectively). In addition, the response rate among patients with the +25AA genotype (75%) was significantly higher than that of other genotypes (24.1% for GG genotype, P=0.004 and 35.7% for AG genotype, P=0.022 respectively). Patients with the -763A/+25G haplotype had a higher risk of non-response to oxaliplatin chemotherapy compared to those carrying the -763G/+25A haplotype (OR 2.672, 95% CI 1.353-5.278, P=0.004). However, no genetic variation was observed at site -413, and no significant association was found between the -1415C>T, +202C>T or +372C>T polymorphisms and chemotherapy response. Therefore, these data suggest that ERCC5 promoter polymorphisms at -763 and +25 may be important predictors of response to oxaliplatin chemotherapy.
Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?

BACKGROUND Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure. METHOD Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method. RESULTS Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone. CONCLUSION The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.
ADULT EDUCATION AND HIGHER EDUCATION - A FOCUS ON TRANSFORMATIVE LEARNING IN UNIVERSITIES

This paper refers to the role of critical thinking in higher education. Scholars claim that enhancing reflective processes should be the benchmark of student education, combining professional preparation with the development of the ability to think critically. According to this thought we argue that adult education and higher education have many common points of interest. Therefore, it would be very useful if specific adult education techniques could be applied in universities. An implementation performed in University of Patras of a contemporary method from adult education field supports this idea. We argue that the application of methods such as “Transformative Learning through Aesthetic Experience” is effective within the students education framework and cultivate critical thinking.
Resting state functional connectivity of the hippocampus associated with neurocognitive function in left temporal lobe epilepsy

The majority of patients with temporal lobe epilepsy (TLE) experience disturbances of episodic memory from structural damage or dysfunction of the hippocampus. The objective of this study was to use functional Magnetic Resonance Imaging (fMRI) to identify regions where resting state connectivity to the left hippocampus (LH) is correlated with neuropsychological measures of verbal memory retention in TLE patients. Eleven left TLE (LTLE) patients and 15 control subjects participated in resting state fMRI scans. All LTLE patients underwent neuropsychological testing. Resting state functional connectivity maps to the LH were calculated for each patient, and subsequently used in a multiple regression analysis with verbal memory retention scores as a covariate. The analysis identified brain regions whose connectivity to the LH was linearly related to memory retention scores across the group of patients. In LTLE patients, right sided (contralateral) clusters in the precuneus and inferior parietal lobule (IPL) exhibited increased connectivity to the LH with increased memory retention score; left sided (ipsilateral) regions in the precuneus and IPL showed increased connectivity to the LH with decreased retention score. Patients with high memory retention scores had greater connectivity between the LH–right parietal clusters than between the LH–left parietal clusters; in contrast, control subjects had significantly and consistently greater LH–left hemisphere than LH–right hemisphere connectivity. Our results suggest that increased connectivity in contralateral hippocampal functional pathways within the episodic verbal memory network represents a strengthening of alternative pathways in LTLE patients with strong verbal memory retention abilities. Hum Brain Mapp 35:735–744, 2014. © 2012 Wiley Periodicals, Inc.
Support Vector Machines for Ranking Learning: The Full and the Truncated Fixed Margin Strategies

Two known SVM-based approaches to ranking learning (ordinal regression estimation, supervised pattern recognition with ordered classes) are scrutinized as different generalizations of the classical principle of finding the optimal discriminant hyperplane in a linear space. Easily verifiable natural conditions are found under which the training result obtained by the computationally much more attractive truncated technique is completely equivalent to the hypothetical strict solution. The numerical procedures are essentially simplified for both techniques.
Single-molecule motions and interactions in live cells reveal target search dynamics in mismatch repair

Significance We integrated single-molecule superresolution imaging with biochemical and genomic approaches to understand how the mismatch repair protein MutS efficiently identifies DNA mismatches during real time in living cells. We show that MutS molecules move fast, exploring the entire nucleoid, but can transition to a slow-moving population that is localized at the replisome even before a mismatch is produced. We show that bacterial MutS must initiate mismatch binding in very close proximity to the replisome. We also show that mismatch detection increases MutS speed, supporting the model for MutS sliding clamp formation after mismatch recognition. Our results provide fundamental insight into the searching behavior of single MutS molecules during DNA replication in live cells. MutS is responsible for initiating the correction of DNA replication errors. To understand how MutS searches for and identifies rare base-pair mismatches, we characterized the dynamic movement of MutS and the replisome in real time using superresolution microscopy and single-molecule tracking in living cells. We report that MutS dynamics are heterogeneous in cells, with one MutS population exploring the nucleoid rapidly, while another MutS population moves to and transiently dwells at the replisome region, even in the absence of appreciable mismatch formation. Analysis of MutS motion shows that the speed of MutS is correlated with its separation distance from the replisome and that MutS motion slows when it enters the replisome region. We also show that mismatch detection increases MutS speed, supporting the model for MutS sliding clamp formation after mismatch recognition. Using variants of MutS and the replication processivity clamp to impair mismatch repair, we find that MutS dynamically moves to and from the replisome before mismatch binding to scan for errors. Furthermore, a block to DNA synthesis shows that MutS is only capable of binding mismatches near the replisome. It is well-established that MutS engages in an ATPase cycle, which is necessary for signaling downstream events. We show that a variant of MutS with a nucleotide binding defect is no longer capable of dynamic movement to and from the replisome, showing that proper nucleotide binding is critical for MutS to localize to the replisome in vivo. Our results provide mechanistic insight into the trafficking and movement of MutS in live cells as it searches for mismatches.
The Memory System: You Can't Avoid It, You Can't Ignore It, You Can't Fake It

Today, computer-system optimization, at both the hardware and software levels, must consider the details of the memory system in its analysis; failing to do so yields systems that are increasingly inefficient as those systems become more complex. This lecture seeks to introduce the reader to the most important details of the memory system; it targets both computer scientists and computer engineers in industry and in academia. Roughly speaking, computer scientists are the users of the memory system, and computer engineers are the designers of the memory system. Both can benefit tremendously from a basic understanding of how the memory system really works: the computer scientist will be better equipped to create algorithms that perform well, and the computer engineer will be better equipped to design systems that approach the optimal, given the resource limitations. Currently, there is consensus among architecture researchers that the memory system is "the bottleneck," and this consensus has held for over a decade. Somewhat inexplicably, most of the research in the field is still directed toward improving the CPU to better tolerate a slow memory system, as opposed to addressing the weaknesses of the memory system directly. This lecture should get the bulk of the computer science and computer engineering population up the steep part of the learning curve. Not every CS/CE researcher/developer needs to do work in the memory system, but, just as a carpenter can do his job more efficiently if he knows a little of architecture, and an architect can do his job more efficiently if he knows a little of carpentry, giving the CS/CE worlds better intuition about the memory system should help them build better systems, both software and hardware.
Fitting Quadratic Curves to Data Points

Fitting quadratic curves (a.k.a. conic sections, or conics) to data points (digitized images) is a fundamental task in image processing and computer vision. This problem reduces to minimization of a certain function over the parameter space of conics. Here we undertake a thorough investigation of that space and the properties of the objective function on it. We determine under what conditions that function is continuous and differentiable. We identify its discontinuities and other singularities and determined what effect those have on the performance of minimization algorithms. Our analysis shows that algebraic parameters of conics are more suitable for minimization procedures than more popular geometric parameters, for a number of reasons. First, the space of parameters is naturally compact, thus their estimated values cannot grow indefinitely causing divergence. Second, with algebraic parameters minimization procedures can move freely and smoothly between conics of different types allowing shortcuts and faster convergence. Third, with algebraic parameters one avoids known issues occurring when the fitting conic becomes a circle. To support our conclusions we prove a dozen of mathematical theorems and provide a plenty of illustrations.
Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector.

UNLABELLED The sodium/iodide symporter (NIS) gene allows convenient reporter imaging with gamma-cameras and free radioiodide. In this study, we investigated the accuracy of this technique for assessing myocardial gene expression in living rats by using a dual-gene adenovirus that expresses both NIS protein and enhanced green fluorescent protein (EGFP). METHODS Rats underwent myocardial injection with the dual-gene adenovirus (Ad.EGFP.NIS) or a control virus (Ad.EGFP). 123I scintigraphy was performed at day 4, and ratios of cardiac counts to mediastinal count were measured. The site of radiouptake was localized by use of dual-isotope 201Tl images, and radioiodide efflux rates were evaluated by dynamic imaging. The dependence of cardiac radiouptake on viral titers and the sensitivity of detection of cardiac radiouptake were investigated at various viral titers. The radioactivity, EGFP, and NIS protein expression sites were compared microscopically. The correlation of image-based uptake with fluorometric measurements of EGFP concentrations was assessed by regression analysis. RESULTS 123I scintigraphy demonstrated clear focal myocardial uptake at the Ad.EGFP. NIS injection site, with relatively slow washout rates (3.3% +/- 0.8%/h), despite the absence of organification. Image-based cardiac uptake increased in a viral titer-dependent manner, with a detection threshold of between 3 x 10(6) and 1 x 10(7) plaque-forming units. Western blotting showed titer-dependent increases in myocardial NIS protein expression. Tissue radioactivity levels approached 12.5-fold control levels and correlated closely with image-based uptake (r = 0.91; P < 0.0001). Histologic analysis confirmed the colocalization of radiouptake, EGFP fluorescence, and NIS staining. Image-based uptake showed a strong correlation with fluorometric measurements of myocardial EGFP concentrations (r = 0.81; P < 0.0001). CONCLUSION Our results demonstrate that convenient myocardial gene imaging with gamma-cameras and radioiodide is feasible with the NIS gene. Moreover, the use of this technique with a dual-gene vector appears to allow accurate assessment of the level of myocardial expression of a second gene of interest.
Evidence for predominant clones in a cyclically parthenogenetic organism provided by combined demographic and genetic analyses

Aphids are particularly interesting models in the study of genetic and demographic components of plant adaptation because of their breeding system which combines parthenogenesis and sexual reproduction (i.e. cyclical parthenogenesis), and the frequent emergence of host‐adapted races reported in this group. In this paper, patterns of host adaptation were assessed on local populations of the aphid Sitobion avenae by following their demographic and genetic structure in a maize field for two consecutive years. The existence of putative generalist (polyphagous) or specialized (host‐adapted) genotypes was also investigated by comparing the genotypic distribution of this aphid on maize and other cultivated host plants, using five microsatellite loci. Although population dynamics revealed strong variation in aphid abundance during the colonization period on maize, two genotypes identified at seven additional microsatellite loci were predominant and exhibited stable frequencies over cropping season and between years. Based on present and earlier studies, these two prevalent genotypes were shown to survive on different host plants other than maize, to colonize large geographical zones and to persist parthenogenetically for several years. All these data strongly suggest that these two genotypes are asexual generalist clones that could have been favoured by agricultural practices encountered in western Europe. Besides these two clones, a continual replacement of rare genotypes was observed on maize in both years. Hypotheses involving selection via aphid–plant interactions and natural enemies were proposed for explaining the disappearance of these genotypes on maize.
Selective targeting of glucagon‐like peptide‐1 signalling as a novel therapeutic approach for cardiovascular disease in diabetes

Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone whose glucose‐dependent insulinotropic actions have been harnessed as a novel therapy for glycaemic control in type 2 diabetes. Although it has been known for some time that the GLP‐1 receptor is expressed in the CVS where it mediates important physiological actions, it is only recently that specific cardiovascular effects of GLP‐1 in the setting of diabetes have been described. GLP‐1 confers indirect benefits in cardiovascular disease (CVD) under both normal and hyperglycaemic conditions via reducing established risk factors, such as hypertension, dyslipidaemia and obesity, which are markedly increased in diabetes. Emerging evidence indicates that GLP‐1 also exerts direct effects on specific aspects of diabetic CVD, such as endothelial dysfunction, inflammation, angiogenesis and adverse cardiac remodelling. However, the majority of studies have employed experimental models of diabetic CVD and information on the effects of GLP‐1 in the clinical setting is limited, although several large‐scale trials are ongoing. It is clearly important to gain a detailed knowledge of the cardiovascular actions of GLP‐1 in diabetes given the large number of patients currently receiving GLP‐1‐based therapies. This review will therefore discuss current understanding of the effects of GLP‐1 on both cardiovascular risk factors in diabetes and direct actions on the heart and vasculature in this setting and the evidence implicating specific targeting of GLP‐1 as a novel therapy for CVD in diabetes.
Lower Urinary Tract Symptoms in Men With Parkinson Disease

Purpose: The aim of this study was to examine the prevalence, presentation, and predictors of lower urinary tract symptoms (LUTS) in men with idiopathic Parkinson disease (PD). Methods: Guided by the Theory of Unpleasant Symptoms, this retrospective exploratory study used data abstracted from admission clinical records of 271 male patients with idiopathic PD enrolled in a movement disorders clinic at a large metropolitan Veterans Affairs Medical Center in the eastern region of the United States. Data from the admission questionnaire, Unified Parkinson’s Disease Rating Scale, and Mini Mental State Examination were abstracted by trained research assistants. Interrater reliability for the abstraction process was 0.99 in a randomly selected 10% sample of records. Descriptive statistics were used to determine the prevalence of LUTS. Logistic regression was used to determine LUTS risk factors and predictors. Results: At least one LUTS was reported by 40.2% of participants. Incontinence was the most prevalent symptom, affecting almost 25% of participants, followed by nocturia (14.8%) and frequency (13.7%). Of the 10 identified risk factors for LUTS, four significant predictors were discovered: number of non-PD medications (p < .05), PD duration (p < .05), number of comorbidities (p < .05), and history of a hernia diagnosis (p < .05). Conclusions: Assessment for LUTS should be a component of every evaluation of a patient with PD. Our findings offer a preliminary profile of the male PD patient with LUTS, which is an important step toward effective screening, detection, and access to care and treatment. Next steps in research include further work to identify predictors of LUTS in both male and female PD populations, explore patient perspectives, begin trials of interventions for LUTS in the PD population, and analyze the economic impact.
Dissection of the XChk 1 Signaling Pathway in Xenopus laevis Embryos

Checkpoint pathways inhibit cyclin-dependent kinases (Cdks) to arrest cell cycles when DNA is damaged or unreplicated. Early embryonic cell cycles of Xenopus laevis lack these checkpoints. Completion of 12 divisions marks the midblastula transition (MBT), when the cell cycle lengthens, acquiring gap phases and checkpoints of a somatic cell cycle. Although Xenopus embryos lack checkpoints prior to the MBT, checkpoints are observed in cell-free egg extracts supplemented with sperm nuclei. These checkpoints depend upon the Xenopus Chk1 (XChk1)-signaling pathway. To understand why Xenopus embryos lack checkpoints, xchk1 was cloned, and its expression was examined and manipulated in Xenopus embryos. Although XChk1 mRNA is degraded at the MBT, XChk1 protein persists throughout development, including pre-MBT cell cycles that lack checkpoints. However, when DNA replication is blocked, XChk1 is activated only after stage 7, two cell cycles prior to the MBT. Likewise, DNA damage activates XChk1 only after the MBT. Furthermore, overexpression of XChk1 in Xenopus embryos creates a checkpoint in which cell division arrests, and both Cdc2 and Cdk2 are phosphorylated on tyrosine 15 and inhibited in catalytic activity. These data indicate that XChk1 signaling is intact but blocked upstream of XChk1 until the MBT.
Objective grading of the loss of pain and touch sensations in leprosy patients.

Two new instruments named Pain/Touch Sensation Testing and Grading devices, which provide standardized and graded stimuli of pain and touch, respectively, were employed to grade the sensory loss at the center of 110 lesions in 97 patients. The grades of sensory loss for pain were 0 (no sensory loss) in 8 lesions, 1 in 6 lesions, 2 in 14 lesions, 3 in 26 lesions, 4 in 19 lesions, and 5 (complete loss) in 37 lesions (total 110 lesions). Grades of sensory loss for touch were 0 in 12 lesions, 1 in 3 lesions, 2 in 5 lesions, 3 in 9 lesions, 4 in 15 lesions, and 5 in 22 lesions (total 66 lesions). Reevaluation done after 2-40 weeks in 46 of these lesions revealed that the grade for pain had decreased in 17 lesions, increased in 4, and remained the same in 25. The grade for loss of touch sensation had decreased in 10, increased in 1, and remained the same in 35. Grading of the sensory loss in most of the 1-cm-square areas of the entire lesion, done in 19 patients (26 lesions), revealed that the sensory loss was not uniform all over the lesion and it was also not maximum at the center of the lesion, though generally it was less at the margin in comparison with the central area. Follow up of 11 of these lesions revealed a decrease in the grades in 7 lesions for both pain and touch sensations, while 2 lesions showed a decrease in the grades for touch sensation only. (ABSTRACT TRUNCATED AT 250 WORDS)