LLukas22/scidocs huggingface dataset:
MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus.

OBJECTIVE
MicroRNA (miRNA) have received increasing attention as posttranscriptional regulators that fine-tune the homeostasis of the inflammatory response. This study aimed to clarify whether miR-125a, which was identified in a pilot expression profiling step, is involved in the inflammatory chemokine pathway in systemic lupus erythematosus (SLE).


METHODS
Independent verification of miR-125a expression in amplified samples from SLE patients and normal controls was performed by TaqMan quantitative polymerase chain reaction (PCR) analysis. A combination of 3 bioinformatic prediction techniques and reporter gene assays was used to identify miR-125a targets. In vitro systems of overexpression by transfection and inducible expression by stimulation were performed to investigate the function of miR-125a, which was followed by real-time quantitative PCR and enzyme-linked immunosorbent assay.


RESULTS
In SLE patients, the expression of miR-125a was reduced and the expression of its predicted target gene, KLF13, was increased. Bioinformatics predicted that miR-125a base-paired with sequences in the 3'-untranslated region of KLF13. Overexpression of miR-125a led to a significant reduction in the expression of RANTES and KLF13. MicroRNA-125a inhibited endogenous KLF13 expression in a dose-dependent manner, as determined using gain- and loss-of-function methods. A luciferase reporter system confirmed the miR-125a binding sites. Notably, miR-125a expression was induced in T cells in a dose- and time-dependent manner. Finally, the introduction of miR-125a into T cells from SLE patients alleviated the elevated RANTES expression.


CONCLUSION
MicroRNA-125a negatively regulates RANTES expression by targeting KLF13 in activated T cells. The underexpression of miR-125a contributes to the elevated expression of RANTES in SLE. Our findings extend the role of miRNA in the pathogenesis of lupus and provide potential strategies for therapeutic intervention.
Learning Particle Physics by Example: Location-Aware Generative Adversarial Networks for Physics Synthesis

Abstract: We provide a bridge between generative modeling in the Machine Learning community and simulated physical processes in High Energy Particle Physics by applying a novel Generative Adversarial Network (GAN) architecture to the production of jet images – 2D representations of energy depositions from particles interacting with a calorimeter. We propose a simple architecture, the Location-Aware Generative Adversarial Network, that learns to produce realistic radiation patterns from simulated high energy particle collisions. The pixel intensities of GAN-generated images faithfully span over many orders of magnitude and exhibit the desired low-dimensional physical properties (i.e., jet mass, n-subjettiness, etc.). We shed light on limitations, and provide a novel empirical validation of image quality and validity of GAN-produced simulations of the natural world. This work provides a base for further explorations of GANs for use in faster simulation in High Energy Particle Physics.
Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.

BACKGROUND
In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies.


OBJECTIVE
To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts.


METHODS
This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (C(max)) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator C(max) and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both C(max) and AUC.


RESULTS
The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%.


CONCLUSIONS
The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts.
Gait analysis following treadmill training with body weight support versus conventional physical therapy: a prospective randomized controlled single blind study

Study design:Single-blind randomized, controlled clinical study.Objectives:To evaluate, using kinematic gait analysis, the results obtained from gait training on a treadmill with body weight support versus those obtained with conventional gait training and physiotherapy.Setting:Thirty patients with sequelae from traumatic incomplete spinal cord injuries at least 12 months earlier; patients were able to walk and were classified according to motor function as ASIA (American Spinal Injury Association) impairment scale C or D.Methods:Patients were divided randomly into two groups of 15 patients by the drawing of opaque envelopes: group A (weight support) and group B (conventional). After an initial assessment, both groups underwent 30 sessions of gait training. Sessions occurred twice a week, lasted for 30 min each and continued for four months. All of the patients were evaluated by a single blinded examiner using movement analysis to measure angular and linear kinematic gait parameters. Six patients (three from group A and three from group B) were excluded because they attended fewer than 85% of the training sessions.Results:There were no statistically significant differences in intra-group comparisons among the spatial–temporal variables in group B. In group A, the following significant differences in the studied spatial–temporal variables were observed: increases in velocity, distance, cadence, step length, swing phase and gait cycle duration, in addition to a reduction in stance phase. There were also no significant differences in intra–group comparisons among the angular variables in group B. However, group A achieved significant improvements in maximum hip extension and plantar flexion during stance.Conclusion:Gait training with body weight support was more effective than conventional physiotherapy for improving the spatial–temporal and kinematic gait parameters among patients with incomplete spinal cord injuries.
Characterization of Biopolymer Based Nanocomposites

The field of nanocomposites is gaining considerable attention due to its potential for providing new materials with extraordinary physical properties compared to traditional composite materials. In ...
Is the prevalence of hypertension in overweight children overestimated?

OBJECTIVES
The aim of this study is to explore different methods for screening and diagnosing hypertension-which definitions and criteria to use-in children and in addition to determine the prevalence of hypertension in Dutch overweight children.


DESIGN
A cross-sectional study performed in the Dutch Child Health Care setting.


SETTING
Four Child Health Care centres in different cities in the Netherlands.


PARTICIPANTS
969 overweight (including obese) and 438 non-overweight children, median age 11.7 years (range 4.1-17.10), 49% boys.


MAIN OUTCOME MEASURES
The main outcome was blood pressure, and the difference in prevalence of hypertension using different criteria for blood pressure interpretation: using the first blood pressure measurement, the mean of two measurements and the lowest of three measurements on two different occasions.


RESULTS
Looking at the first measurement alone, 33% of overweight and 21% of non-overweight children had hypertension. By comparing the mean of the first two measurements with reference values, 28% of overweight children and 16% of non-overweight children had hypertension. Based on the lowest of three consecutive measurements, the prevalence decreased to 12% among overweight children and 5% among non-overweight children at visit one and at visit two 4% of overweight children still had hypertension.


CONCLUSIONS
The prevalence of hypertension is highly dependent on the definitions and criteria used. We found a prevalence of 4% in overweight children, which is considerably lower than suggested by recent literature (4%-33%). This discrepancy can be explained by our more strict definition of hypertension. However, to draw any conclusions on the prevalence, normal values using the same definition of hypertension should be established. Despite the low prevalence, we recommend measuring blood pressure in all overweight children in view of later cardiovascular morbidity and mortality.
Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer

Background:This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).Methods:Ninety patients were randomised to a standard dose of wPTX (80 mg m−2) or an escalated dose of wPTX (80–120 mg m−2) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8.Results:The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34).Conclusion:Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.
Boosted decision trees as an alternative to artificial neural networks for particle identification

The efficacy of particle identification is compared using artificial neutral networks and boosted decision trees. The comparison is performed in the context of the MiniBooNE, an experiment at Fermilab searching for neutrino oscillations. Based on studies of Monte Carlo samples of simulated data, particle identification with boosting algorithms has better performance than that with artificial neural networks for the MiniBooNE experiment. Although the tests in this paper were for one experiment, it is expected that boosting algorithms will find wide application in physics. r 2005 Elsevier B.V. All rights reserved. PACS: 29.85.+c; 02.70.Uu; 07.05.Mh; 14.60.Pq
Inhibition of IKs channels by HMR 1556

Chromanol HMR 1556 [(3R,4S)-(+)-N-[3-hydroxy-2,2-dimethyl-6-(4,4,4-trifluorobutoxy)chroman-4-yl]-N-methylmethanesulfonamide], a novel inhibitor of the slow component of the delayed outward current in heart muscle cells (I Ks), has been characterized in several in-vitro systems. mRNA encoding for the human protein minK was injected into Xenopus oocytes, leading to the expression of I Ks channels. HMR 1556 inhibited this current half-maximally at a concentration of 120 nmol/l (IC50). Expression of the K+ channels Herg, Kv1.5, Kv1.3 and Kir2.1, and also the cationic current HCN2, were blocked little or not at all by 10 µmol/l HMR 1556. In isolated ventricular myocytes from the guinea pig the whole-cell patch-clamp method revealed inhibition of the I Ks current with an IC50 of 34 nmol/l. Other current components, like I Kr and I K1, were only slightly blocked at an HMR 1556 concentration of 10 µmol/l, whereas 10 µmol/l HMR 1556 inhibited the transient outward current I to and the sustained outward current I sus in rat ventricular myocytes by 25% and 36%, respectively. The L-type Ca2+ channel in guinea pig cardiomyocytes was blocked by 10 µmol/l HMR 1556 by 31%. Guinea pig right papillary muscles were investigated by the micropuncture technique at various pacing rates. In the frequency range of 0.5–7 Hz HMR 1556 (1 µmol/l) caused a prolongation of the action potential duration at 90% repolarization (APD90) by 19%–27%. In the presence of isoproterenol (10 µmol/l) the prolongation of the APD90 was more pronounced at low pacing rates (47% at 0.5 Hz and 35% at 1 Hz, compared with 25% at 7 Hz). The monophasic action potential was recorded in Langendorff-perfused guinea pig hearts. In spontaneously beating preparations, HMR 1556, at 0.1 µmol/l and 1 µmol/l, prolonged the MAPD90 by 3% and 10%, respectively, with no further prolongation at 10 µmol/l. The prolongation was much greater at low pacing rates [25% at 100 beats per min (bpm) and 13% at 150 bpm] than at fast pacing rates (9% at 350 bpm). The left ventricular pressure LVPmax was not affected at 1 µmol/l HMR 1556, but it decreased by 15% at 10 µmol/l. Other parameters, like the heart rate and coronary flow, were only slightly decreased at 1 µmol/l HMR 1556. In conclusion, HMR 1556 is a potent and selective inhibitor of the I Ks current in guinea pig ventricular myocytes. The prolongation of the action potential duration is maintained at fast pacing rates.
Frequent item set mining

Frequent item set mining is one of the best known and most popular data mining methods. Originally developed for market basket analysis, it is used nowadays for almost any task that requires discovering regularities between (nominal) variables. This paper provides an overview of the foundations of frequent item set mining, starting from a definition of the basic notions and the core task. It continues by discussing how the search space is structured to avoid redundant search, how it is pruned with the a priori property, and how the output is reduced by confining it to closed or maximal item sets or generators. In addition, it reviews some of the most important algorithmic techniques and data structures that were developed to make the search for frequent item sets as efficient as possible. C © 2012 Wiley Periodicals, Inc.
Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease.

RATIONALE
Accurate prediction of mortality helps select patients for interventions aimed at improving outcome.


OBJECTIVES
Because chronic obstructive pulmonary disease is characterized by low-grade systemic inflammation, we hypothesized that addition of inflammatory biomarkers to established predictive factors will improve accuracy.


METHODS
A total of 1,843 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study were followed for 3 years. Kaplan-Meier curves, log-rank analysis, and Cox proportional hazards analyses determined the predictive value for mortality of clinical variables, while C statistics assessed the added discriminative power offered by addition of biomarkers.


MEASUREMENTS AND MAIN RESULTS
At recruitment we measured anthropometrics, spirometry, 6-minute walk distance, dyspnea, BODE index, history of hospitalization, comorbidities, and computed tomography scan emphysema. White blood cell and neutrophil counts, serum or plasma levels of fibrinogen, chemokine ligand 18, surfactant protein D, C-reactive protein, Clara cell secretory protein-16, IL-6 and -8, and tumor necrosis factor-α were determined at recruitment and subsequent visits. A total of 168 of the 1,843 patients (9.1%) died. Nonsurvivors were older and had more severe airflow limitation, increased dyspnea, higher BODE score, more emphysema, and higher rates of comorbidities and history of hospitalizations. The best predictive model for mortality using clinical variables included age, BODE, and hospitalization history (C statistic of 0.686; P < 0.001). One single biomarker (IL-6) significantly improved the C statistic to 0.708, but this was further improved to 0.726 (P = 0.003) by the addition of all biomarkers.


CONCLUSIONS
The addition of a panel of selected biomarkers improves the ability of established clinical variables to predict mortality in chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).
From cathode rays to alpha particles to quantum of action: A rational reconstruction of structure of the atom and its implications for chemistry textbooks

Research in science education has recognized the importance of the history and philosophy of science. Given this perspective, it is important to analyze chemistry textbooks, at the freshman college level, to determine the degree to which they deal with recent developments in the history and philosophy of science. This study has the following objectives: of a (a) elaboration framework, based on a rational reconstruction of developments that led to the formulation of atomic models by Thomson, Rutherford, and Bohr; of eight criteria based on the framework (b) formulation that could be useful in the evaluation of chemistry textbooks; and of the textbooks (c) evaluation based on the criteria. Twenty-three textbooks were evaluated on the eight criteria. Results obtained show that most textbooks emphasize experimental details based on observations, leading to the presentation of scientific progress as a rhetoric of conclusions, based on irrevocable truths. Such an understanding lacks the conceptualization of the heuristic principles that led the scientists to design and interpret their experiments. For example, in the case of J. J. Thomson’s work, besides the experimental details of cathode ray experiments (emphasized by most textbooks), the “heuristic principle” involved the testing of rival hypotheses, namely a determination of the mass-to-charge ratio would have helped to identify cathode ray particles as an ion or a universal charged particle. Most textbooks presented the experimental details, without the conceptualization that progress in science is based on competing frameworks of understanding that clash in the face of evidence. It is concluded that textbooks should emphasize not only the experimental details but also the “heuristic principles” required to “structure inquiry.” q 1998 John Wiley & Sons, Inc. Sci Ed 82:527–552, 1998.
Elevated Frequencies of Circulating Th22 Cell in Addition to Th17 Cell and Th17/Th1 Cell in Patients with Acute Coronary Syndrome

BACKGROUND
Atherosclerosis is a chronic inflammatory disease mediated by immune cells. Th22 cells are CD4(+) T cells that secret IL-22 but not IL-17 or IFN-γ and are implicated in the pathogenesis of inflammatory disease. The roles of Th22 cells in the pathophysiologic procedures of acute coronary syndrome (ACS) remain unclear. The purpose of this study is to investigate the profile of Th22, Th17 and Th17/Th1 cells in ACS patients, including unstable angina (UA) and acute myocardial infarction (AMI) patients.


DESIGN AND METHODS
In this study, 26 AMI patients, 16 UA patients, 16 stable angina (SA) patients and 16 healthy controls were included. The frequencies of Th22, Th17 and Th17/Th1 cells in AMI, UA, SA patients and healthy controls were examined by flow cytometry. Plasma levels of IL-22, IL-17 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA).


RESULTS
Th22, Th17 and Th17/Th1 cells were significantly increased in AMI and UA patients compared with SA patients and healthy controls. Moreover, plasma IL-22 level was significantly elevated in AMI and UA patients. In addition, Th22 cells correlated positively with IL-22 as well as Th17 cells in AMI and UA patients.


CONCLUSION
Our findings showed increased frequencies of both Th22 and Th17 cells in ACS patients, which suggest that Th22 and Th17 cells may play a potential role in plaque destabilization and the development of ACS.
Phishing threat avoidance behaviour: An empirical investigation

Phishing is an online identity theft that aims to steal sensitive information such as username, password and online banking details from its victims. Phishing education needs to be considered as a means to combat this threat. This paper reports on a design and development of a mobile game prototype as an educational tool helping computer users to protect themselves against phishing attacks. The elements of a game design framework for avoiding phishing attacks were used to address the game design issues. Our mobile game design aimed to enhance the users' avoidance behaviour through motivation to protect themselves against phishing threats. A think-aloud study was conducted, along with a preand post-test, to assess the game design framework though the developed mobile game prototype. The study results showed a significant improvement of participants' phishing avoidance behaviour in their post-test assessment. Furthermore, the study findings suggest that participants' threat perception, safeguard effectiveness, self-efficacy, perceived severity and perceived susceptibility elements positively impact threat avoidance behaviour, whereas safeguard cost had a negative impact on it. © 2016 Elsevier Ltd. All rights reserved.
A computational framework for conceptual blending

Article history: Received 1 September 2016 Received in revised form 3 November 2017 Accepted 23 November 2017 Available online 2 December 2017
Ranking in evolving complex networks

Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithmsperform, andwhich are their possible biases thatmay impair their effectiveness. Many popular ranking algorithms (such as Google’s PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks.We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes. © 2017 Elsevier B.V. All rights reserved.