Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased DNA Methyltransferase Expression Is Associated with an Early Stage of Human Hepatocarcinogenesis

The present study was designed to determine whether changes in DNA methyltransferase (DNA MTase) expression are involved in hepatocarcinogenesis. We examined DNA MTase expression in normal liver tissue (with no remarkable histological findings), liver tissue showing chronic hepatitis or cirrhosis, which are generally thought to be precancerous conditions, and hepatocellular carcinomas (HCCs) using the reverse‐transcriptase polymerase chain reaction assay. DNA MTase mRNA levels were significantly higher in liver tissue showing chronic hepatitis and cirrhosis (DNA MTase mRNA/β‐actin mRNA ratio=0.30±0.22, n=24, P<0.01) than in normal liver tissue either from patients with liver metastatic lesions of colonic cancer (0.14±0.05, n= 6) or from patients with HCCs (0.16±0.07, n= 3). DNA MTase mRNA levels were even higher in HCC tissue (0.34±0.18, n=29). These results suggest that increased DNA MTase expression may be an early event during hepatocar‐cinogenesis. DNA MTase is a potential target for HCC preventive therapy.
The neural networks of subjectively evaluated emotional conflicts

Previous work on the neural underpinnings of emotional conflict processing has largely focused on designs that instruct participants to ignore a distracter which conflicts with a target. In contrast, this study investigated the noninstructed experience and evaluation of an emotional conflict, where positive or negative cues can be subjectively prioritized. To this end, healthy participants freely watched short film scenes that evoked emotional conflicts while their BOLD responses were measured. Participants' individual ratings of conflict and valence perception during the film scenes were collected immediately afterwards, and the individual ratings were regressed against the BOLD data. Our analyses revealed that (a) amygdala and medial prefrontal cortex were significantly involved in prioritizing positive or negative cues, but not in subjective evaluations of conflict per se, and (b) superior temporal sulcus (STS) and inferior parietal lobule (IPL), which have been implicated in social cognition and emotion control, were involved in both prioritizing positive or negative cues and subjectively evaluating conflict, and may thus constitute “hubs” or “switches” in emotional conflict processing. Psychophysiological interaction (PPI) analyses further revealed stronger functional connectivity between IPL and ventral prefrontal—medial parietal areas in prioritizing negative cues, and stronger connectivity between STS and dorsal‐rostral prefrontal—medial parietal areas in prioritizing positive cues. In sum, our results suggest that IPL and STS are important in the subjective evaluation of complex conflicts and influence valence prioritization via prefrontal and parietal control centers. Hum Brain Mapp 37:2234–2246, 2016. © 2016 Wiley Periodicals, Inc.
LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

PURPOSE Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness. PATIENTS AND METHODS Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3–1), we report LGR5 and R-spondin (RSPO1–3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients). RESULTS Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%–72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%–97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005). CONCLUSION We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC.
Measuring Estimator's Credibility: Noncredibility Index

Many estimators and filters provide assessments (e.g., MSE matrices) of their own estimation errors. They are, however, obtained based on simplifying assumptions that are not necessarily valid. Then the questions are: Are these self-assessments trustable? How trustable are they? We referred to these problems as the credibility of the estimators/filters. Solid technical answers to the first question are provided in two companion papers for this conference based on statistical hypothesis testing. Complementary to those, we answer the second question in this paper by proposing a family of metrics, called noncredibility indices (NCI) and inclination indicators (I2), that measure how credible various self-assessments are. We show that the NCI and I have many desirable properties and are more appropriate than a bunch of possible alternatives and by far superior to a heuristic measure currently in use explicitly or implicitly. We also provide simple numerical examples to illustrate the application of the metrics proposed
Relationships Between Ring-Width Variation and Soil Nutrient Availability at the Tree Scale

Within the framework of the linear aggregate model of dendrochronology, the potential role of soil nutrient availability in explaining multi -decadal variation in radial growth at the tree level was studied in the central Spanish Pyrenees. Increment cores were collected from 20 mature Pinus uncinata Ram. and analyzed dendrochronologically. One ion -exchange resin capsule was buried within the root zone of each sampled tree for just over eight months. The resins were chemically extracted and measured for NH4, NO PO4, Ca, and K. Statistical relationships between indexed tree growth and soil nutrient availability were determined with regression analysis and bivariate plots. The single most important soil nutrient with respect to decadal -scale dendrochronological tree -growth variables in this study was N in the form NO which explained 22% of variation of trend in growth since 1950. The 20 values of NO3 availability fell into two subgroups, one of trees with relatively higher NO3 availability and the other with lower NO3 availability. When the tree -growth data were grouped based on NO3 availability, the two resultant index chronologies had different lowfrequency features since 1950. Trees with low NO3 availability have been growing as expected based on past growth, but trees with high NO availability have been growing better than expected. Measuring and analyzing soil nutrient availability at the tree level might enhance environmental applications of dendrochronological research. With soils information at this spatial scale, it is possible to distinguish between subgroups of trees within a tree -ring site and thereby construct subchronologies that differ significantly, especially for variation at the decadal scale. Subsitechronologies may then lead to different and presumably more informative environmental interpretations relative to those based on a full -site chronology.
A comparison of sliding mode and unknown input observers for fault reconstruction

This paper compares the use of a recently proposed sliding mode fault detection and isolation scheme with a linear scheme based on an unknown input observer. Both methods seek to reconstruct actuator and sensor fault signals for a class of uncertain systems. Although the explicit details of the two approaches appear quite different, an underlying link between them is exposed and investigated. The methods are compared on data collected from a laboratory scale crane rig on which (known) faults were deliberately introduced.
Food Choice and Nutrition: A Social Psychological Perspective

In this Special Issue, entitled “Food choice and Nutrition: A Social Psychological Perspective”, three broad themes have been identified: (1) social and environmental influences on food choice; (2) psychological influences on eating behaviour; and (3) eating behaviour profiling. The studies that addressed the social and environmental influences indicated that further research would do well to promote positive food choices rather than reduce negative food choices; promote the reading and interpretation of food labels and find ways to effectively market healthy food choices through accessibility, availability and presentation. The studies on psychological influences found that intentions, perceived behavioural control, and confidence were predictors of healthy eating. Given the importance of psychological factors, such as perceived behavioural control and self-efficacy, healthy eating interventions should reduce barriers to healthy eating and foster perceptions of confidence to consume a healthy diet. The final theme focused on the clustering of individuals according to eating behaviour. Some “types” of individuals reported more frequent consumption of fast foods, ready meals or convenience meals or greater levels of disinhibition and less control over food cravings. Intervention designs which make use of multi-level strategies as advocated by the Ecological Model of Behaviour change that proposes multi-level (combining psychological, social and environmental) strategies are likely to be more effective in reaching and engaging individuals susceptible to unhealthy eating habits than interventions operating on a single level.
The Number of Nilpotent Semigroups of Degree 3

A semigroup is nilpotent of degree $3$ if it has a zero, every product of $3$ elements equals the zero, and some product of $2$ elements is non-zero. It is part of the folklore of semigroup theory that almost all finite semigroups are nilpotent of degree $3$. We give formulae for the number of nilpotent semigroups of degree $3$ on a set with $n\in\mathbb{N}$ elements up to equality, isomorphism, and isomorphism or anti-isomorphism. Likewise, we give formulae for the number of nilpotent commutative semigroups on a set with $n$ elements up to equality and up to isomorphism.
ublethal effects of copper sulphate compared to copper anoparticles in rainbow trout ( Oncorhynchus mykiss ) at low pH : hysiology and metal accumulation enan

A few studies have investigated the interaction between copper toxicity and water pH in fishes, but little is known about the effects of acidic pH on the toxicity of copper nanoparticles (Cu-NPs). This study aimed to describe the sub-lethal toxic effects of Cu-NPs compared to CuSO4 at neutral and acidic water pH values in juvenile rainbow trout. Fish were exposed in triplicate (3 tanks/treatment) to control (no added Cu), or 20 g l−1 of either Cu as CuSO4 or Cu-NPs, at pH 7 and 5 in a semi-static aqueous exposure regime for up to 7 days. Acidification of the water altered the mean primary particle size (at pH 7, 60 ± 2 nm and pH 5, 55 ± 1 nm) and dialysis experiments to measure dissolution showed an increased release of dissolved Cu from Cu-NPs at pH 5 compared to pH 7. Copper accumulation was observed in the gills of trout exposed to CuSO4 and Cu-NPs at pH 7 and 5, with a greater accumulation from the CuSO4 treatment than Cu-NPs at each pH. The liver also showed Cu accumulation with both Cu treatments at pH 7 only, whereas, the spleen and kidney did not show measurable accumulation of Cu at any of the water pH values. Exposure to acid water caused changes in the ionoregulatory physiology of control fish and also altered the observed effects of Cu exposure; at pH 5, branchial Na+/K+-ATPase activity was greater than at pH 7 and the inhibition of Na+/K+-ATPase activity caused by exposure to CuSO4 at pH 7 was also not observed. There were some changes in haematology and depletion of plasma Na+ at pH 7 and 5 due to Cu exposure, but there were few material-type or pH effects. Overall, the data show that the accumulation of Cu is greater from CuSO4 than Cu-NPs; however, understanding of the effects of low pH on bioavailability of CuSO4 may not be directly transferred to Cu-NPs without further consideration of the physico-chemical behaviour of Cu-NPs in acid water. © 2016 Elsevier B.V. All rights reserved.
International amphibian micronucleus standardized procedure (ISO 21427‐1) for in vivo evaluation of double‐walled carbon nanotubes toxicity and genotoxicity in water

Considering the important production of carbon nanotubes (CNTs), it is likely that some of them will contaminate the environment during each step of their life cycle. Nevertheless, there is little known about their potential ecotoxicity. Consequently, the impact of CNTs on the environment must be taken into consideration. This work evaluates the potential impact of well characterized double‐walled carbon nanotubes (DWNTs) in the amphibian larvae Xenopus laevis under normalized laboratory conditions according to the International Standard micronucleus assay ISO 21427‐1:2006 for 12 days of half‐static exposure to 0.1–1–10 and 50 mg L−1 of DWNTs in water. Two different endpoints were carried out: (i) toxicity (mortality and growth of larvae) and (ii) genotoxicity (induction of micronucleated erythrocytes). Moreover, intestine of larvae were analyzed using Raman spectroscopy. The DWNTs synthetized by catalytic chemical vapor deposition (CCVD) were used as produce (experiment I) and the addition of Gum Arabic (GA) was investigated to improve the stability of the aqueous suspensions (experiment II). The results show growth inhibition in larvae exposed to 10 and 50 mg L−1 of DWNTs with or without GA. No genotoxicity was evidenced in erythrocytes of larvae exposed to DWNTs, except to 1 mg L−1 of DWNTs with GA suggesting its potential effect in association with DWNTs at the first nonacutely toxic concentration. The Raman analysis confirmed the presence of DWNTs into the lumen of intestine but not in intestinal tissues and cells, nor in the circulating blood of exposed larvae. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.
On the expected size of minimum-energy path-preserving topologies for wireless multi-hop networks

Topology Control (TC) algorithms for multi-hop wireless networks create a connected communication subgraph that satisfies some topological properties by assigning appropriate transmission power to each node. A topology is said to be minimum-energy path-preserving if it preserves minimum energy paths between every pair of nodes. Creating minimum-energy path-preserving sparse topologies is a fundamental research problem in TC that has been addressed in several recent research works. Although sparseness is a key metric in comparing the performance of such algorithms, none of these prior works provides analytical models to determine the sparseness. In this paper, we provide a generic analytical model for evaluating sparseness of such topologies. The derived analytical expressions are useful in determining topology size without running simulations or prior to the deployment of real systems. Moreover, we demonstrate how to analytically couple sparseness of topologies with the radio transceiver parameters. The analytical expressions are validated through extensive simulation experiments.
Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate

Background and objective: Through interruption of maintenance treatment with 6‐mercaptopurine (6MP), toxicity after high‐dose methotrexate (HDMTX) may compromise the efficiency of the treatment of children with acute lymphocytic leukaemia (ALL). We investigated the influence of polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene and coadministration of antimetabolites on post‐HDMTX toxicity.
Primate embryogenesis predicts the hallmarks of human naïve pluripotency

ABSTRACT Naïve pluripotent mouse embryonic stem cells (ESCs) resemble the preimplantation epiblast and efficiently contribute to chimaeras. Primate ESCs correspond to the postimplantation embryo and fail to resume development in chimaeric assays. Recent data suggest that human ESCs can be ‘reset’ to an earlier developmental stage, but their functional capacity remains ill defined. Here, we discuss how the naïve state is inherently linked to preimplantation epiblast identity in the embryo. We hypothesise that distinctive features of primate development provide stringent criteria to evaluate naïve pluripotency in human and other primate cells. Based on our hypothesis, we define 12 key hallmarks of naïve pluripotency, five of which are specific to primates. These hallmarks may serve as a functional framework to assess human naïve ESCs. Summary: This Hypothesis article highlights several fundamental differences between rodent and primate early development and exploits these to predict key hallmarks of naïve pluripotency in primates.
Infiltration of a Mesothelioma by IFN-γ-Producing Cells and Tumor Rejection after Depletion of Regulatory T Cells1

Depletion of CD4+CD25+Foxp3+ regulatory T cells (CD25+ Treg) with an anti-CD25 Ab results in immune-mediated rejection of tolerogenic solid tumors. In this study, we have examined the immune response to a mesothelioma tumor in mice after depletion of CD25+ cells to elucidate the cellular mechanisms of CD25+ Treg, a subject over which there is currently much conjecture. Tumor rejection was found to be primarily due to the action of CD8+ T cells, although CD4+ cells appeared to play some role. Depletion of CD25+ cells resulted in an accumulation in tumor tissue of CD4+ and CD8+ T cells and NK cells that were producing the potent antitumor cytokine IFN-γ. Invasion of tumors by CD8+ T cells was partially dependent on the presence of CD4+ T cells. Although a significant increase in the proliferation and number of tumor-specific CD8+ T cells was observed in lymph nodes draining the tumor of anti-CD25-treated mice, this effect was relatively modest compared with the large increase in IFN-γ-producing T cells found in tumor tissue, which suggests that the migration of T cells into tumor tissue may also have been altered. Depletion of CD25+ cells did not appear to modulate antitumor CTL activity on a per cell basis. Our data suggests that CD25+ Treg limit the accumulation of activated T cells producing IFN-γ in the tumor tissue and, to a lesser extent, activation and/or rate of mitosis of tumor-specific T cells in lymph nodes.
On‐line software version change using state transfer between processes

The usual way of installing a new version of a piece of software is to shut down the running program and then install the new version. This necessitates a sometimes unacceptable delay during which service is denied to the users of the software. An on‐line software replacement system replaces parts of the software while it is in execution, thus eliminating the shutdown. In this paper, we describe a system for on‐line software version change for software written in the C language. When the change is initiated by the user, the system instantiates a new process with the new version of the software, transfers state from the old process to the new one at an appropriate time, and transfers the control to the new process. The user sees a minimal delay in this switchover.
Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States.

UNLABELLED IMPORTANCE It is not known whether hospital and surgeon volumes have an association with readmission among patients undergoing pancreatoduodenectomy. OBJECTIVE To evaluate patient-, surgeon-, and hospital-level factors associated with readmission. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data with cases diagnosed from January 1, 1998, to December 31, 2005, and followed up until December 2007. Population-based cancer registry data were linked to Medicare data for the corresponding patients. A total of 1488 unique individuals who underwent a pancreatoduodenectomy were identified. INTERVENTIONS Undergoing pancreatoduodenectomy at hospitals classified by volume of pancreatoduodenectomy procedures performed at the facility were either very-low, low, medium, or high volume. Undergoing pancreatoduodenectomy by surgeons classified by volume of pancreatoduodenectomy procedures performed by the surgeon were either very-low, low, medium, or high volume. MAIN OUTCOMES AND MEASURES In-hospital morbidity, mortality, and 30-day readmission were examined. RESULTS The median age was 74 years, and 1436 patients (96.5%) had a least 1 medical comorbidity. Patients were treated by 575 distinct surgeons at 298 distinct hospitals. Length of stay was longest (median, 17 days) and 90-day mortality highest (17.2%) at very-low-volume hospitals (P < .001). Among all pancreatoduodenectomy patients, 292 (21.3%) were readmitted within 30 days of discharge. There was no effect of surgeon volume and a modest effect of hospital volume (odds ratio for highest- vs lowest-volume quartiles, 1.85; 95% CI, 1.22-2.80; P = .02). The presence of significant preoperative medical comorbidities was associated with an increased risk for hospital readmission after pancreatoduodenectomy. A comorbidity score greater than 13 had a pronounced effect on the chance of readmission following pancreatoduodenectomy (odds ratio, 2.06; 95% CI, 1.56-2.71; P < .001). The source of variation in readmission was primarily attributable to patient-related factors (95.4%), while hospital factors accounted for 4.3% of the variability and physician factors for only 0.3%. CONCLUSIONS AND RELEVANCE Nearly 1 in 5 patients are readmitted following pancreatoduodenectomy. While variation in readmission is, in part, attributable to differences among hospitals, the largest share of variation was found at the patient level.
Absolute convergence: true trees from short sequences

Fast-converging methods for reconstructing phylogenetic trees require that the sequences characterizing the taxa be of only polynomial length, a major asset in practice, since real-life sequences are of bounded length. However, of the half-dozen such methods proposed over the last few years, only two fulfill this condition without requiring knowledge of typically unknown parameters, such as the evolutionary rate(s) used in the model; this additional requirement severely limits the applicability of the methods. We say that methods that need such knowledge demonstrate relative fast convergence, since they rely upon an oracle. We focus on the class of methods that do not require such knowledge and thus demonstrate absolute fast convergence. We give a very general construction scheme that not only turns any relative fast-converging method into an absolute fast-converging one, but also turns any statistically consistent method that converges from sequence of length &Ogr;(e&Ogr;(diam(T))) into an absolute fast-converging method.