LLukas22/scidocs huggingface dataset:
Olaparib does not cause clinically relevant QT/QTc interval prolongation in patients with advanced solid tumours: results from two phase I studies

Some therapeutic agents in oncology can be causally associated with specific cardiovascular events including QT/QTc interval prolongation. We investigated the effect of multiple dosing of the oral poly (ADP-ribose)-polymerase (PARP) inhibitor, olaparib (tablet formulation) on QT/QTc interval. Two phase I, open-label, three-part studies (NCT01921140 [study 4] and NCT01900028 [study 7]) were conducted in adults with refractory/resistant advanced solid tumours. In both studies, parts A and B assessed the QT/QTc interval effects of single-dose oral olaparib 100 (study 4) or 300 (study 7) mg and multiple-dose olaparib 300 mg bid for 5 days, respectively, while part C evaluated continued access to olaparib for additional safety analyses. An ANCOVA model tested the primary objective of multiple-dose effects of olaparib on QT interval corrected using Fridericia’s formula (QTcF). Data from 119 and 109 patients were pooled from parts A and B, respectively, for QT/QTc analysis. At pre-dose and up to 12 h post-dose, the upper limits of the 90 % confidence intervals (CIs) for the difference in QTcF least squares means after olaparib multiple dosing versus control (day −1) were <10 ms, suggesting a lack of clinically relevant effect on cardiac repolarization. A slight shortening of QTcF was observed at most time points versus control. QTcF results for the individual studies and single-dose olaparib paralleled the primary multiple-dose pooled analysis, with upper limits of the 90 % CIs < 10 ms. Olaparib tablets administered as multiple or single doses had no clinically significant effect on QT/QTc interval.
Long-term exposure to air pollution and incidence of cardiovascular events in women.

BACKGROUND
Fine particulate air pollution has been linked to cardiovascular disease, but previous studies have assessed only mortality and differences in exposure between cities. We examined the association of long-term exposure to particulate matter of less than 2.5 microm in aerodynamic diameter (PM2.5) with cardiovascular events.


METHODS
We studied 65,893 postmenopausal women without previous cardiovascular disease in 36 U.S. metropolitan areas from 1994 to 1998, with a median follow-up of 6 years. We assessed the women's exposure to air pollutants using the monitor located nearest to each woman's residence. Hazard ratios were estimated for the first cardiovascular event, adjusting for age, race or ethnic group, smoking status, educational level, household income, body-mass index, and presence or absence of diabetes, hypertension, or hypercholesterolemia.


RESULTS
A total of 1816 women had one or more fatal or nonfatal cardiovascular events, as confirmed by a review of medical records, including death from coronary heart disease or cerebrovascular disease, coronary revascularization, myocardial infarction, and stroke. In 2000, levels of PM2.5 exposure varied from 3.4 to 28.3 microg per cubic meter (mean, 13.5). Each increase of 10 microg per cubic meter was associated with a 24% increase in the risk of a cardiovascular event (hazard ratio, 1.24; 95% confidence interval [CI], 1.09 to 1.41) and a 76% increase in the risk of death from cardiovascular disease (hazard ratio, 1.76; 95% CI, 1.25 to 2.47). For cardiovascular events, the between-city effect appeared to be smaller than the within-city effect. The risk of cerebrovascular events was also associated with increased levels of PM2.5 (hazard ratio, 1.35; 95% CI, 1.08 to 1.68).


CONCLUSIONS
Long-term exposure to fine particulate air pollution is associated with the incidence of cardiovascular disease and death among postmenopausal women. Exposure differences within cities are associated with the risk of cardiovascular disease.
Understanding knowledge sharing activities in free/open source software projects: An empirical study

Free/Open Source Software (F/OSS) projects are people-oriented and knowledge intensive software development environments. Many researchers focused on mailing lists to study coding activities of software developers. How expert software developers interact with each other and with non-developers in the use of community products have received little attention. This paper discusses the altruistic sharing of knowledge between knowledge providers and knowledge seekers in the Developer and User mailing lists of the Debian project. We analyze the posting and replying activities of the participants by counting the number of email messages they posted to the lists and the number of replies they made to questions others posted. We found out that participants interact and share their knowledge a lot, their positing activity is fairly highly correlated with their replying activity, the characteristics of posting and replying activities are different for different kinds of lists, and the knowledge sharing activity of self-organizing Free/Open Source communities could best be explained in terms of what we called ‘‘Fractal Cubic Distribution’’ rather than the power-law distribution mostly reported in the literature. The paper also proposes what could be researched in knowledge sharing activities in F/OSS projects mailing list and for what purpose. The research findings add to our understanding of knowledge sharing activities in F/OSS projects. 2007 Elsevier Inc. All rights reserved.
Degrading Endocrine Disrupting Chemicals from Wastewater by TiO Photocatalysis: A Review

Widespread concerns continue to be raised about the impacts of exposure to chemical compounds with endocrine disrupting activities. To date, the percolation of endocrine disrupting chemical (EDC) effluent into the aquatic system remains an intricate challenge abroad the nations. With the innovation of advanced oxidation processes (AOPs), there has been a consistent growing interest in this research field. Hence, the aim of this paper is to focus one such method within the AOPs, namely, heterogeneous photocatalysis and how it is used on the abatement of EDCs, phthalates, bisphenol A and chlorophenols in particular, using TiO2-based catalysts. Degradation mechanisms, pathways, and intermediate products of various EDCs for TiO2 photocatalysis are described in detail. The effect of key operational parameters on TiO2 photocatalytic degradation of various EDCs is then specifically covered. Finally, the future prospects together with the challenges for the TiO2 photocatalysis on EDCs degradation are summarized and discussed.
A survey on intelligent routing protocols in wireless sensor networks

This paper surveys intelligent routing protocols which contribute to the optimization of network lifetime in wireless sensor networks (WSNs). Different from other surveys on routing protocols for WSNs, this paper first puts forward new ideas on the definition of network lifetime. Then, with a view to prolonging network lifetime, it discusses the routing protocols based on such intelligent algorithms as reinforcement learning (RL), ant colony optimization (ACO), fuzzy logic (FL), genetic algorithm (GA), and neural networks (NNs). Intelligent algorithms provide adaptive mechanisms that exhibit intelligent behavior in complex and dynamic environments like WSNs. Inspired by such an idea, some intelligent routing protocols have recently been designed for WSNs. Under each category, it discusses the representative routing algorithms and further analyzes the performance of network lifetime defined in three aspects. This paper intends to give assistance in the optimization of network lifetime in WSNs, together with offering a guide for the collaboration between WSNs and computational intelligence (CI). & 2013 Published by Elsevier Ltd. 68 69 70 71
Medical Therapies for Adult Chronic Sinusitis: A Systematic Review.

IMPORTANCE
Chronic sinusitis is a common inflammatory condition defined by persistent symptomatic inflammation of the sinonasal cavities lasting longer than 3 months. It accounts for 1% to 2% of total physician encounters and is associated with large health care expenditures. Appropriate use of medical therapies for chronic sinusitis is necessary to optimize patient quality of life (QOL) and daily functioning and minimize the risk of acute inflammatory exacerbations.


OBJECTIVE
To summarize the highest-quality evidence on medical therapies for adult chronic sinusitis and provide an evidence-based approach to assist in optimizing patient care.


EVIDENCE REVIEW
A systematic review searched Ovid MEDLINE (1947-January 30, 2015), EMBASE, and Cochrane Databases. The search was limited to randomized clinical trials (RCTs), systematic reviews, and meta-analyses. Evidence was categorized into maintenance and intermittent or rescue therapies and reported based on the presence or absence of nasal polyps.


FINDINGS
Twenty-nine studies met inclusion criteria: 12 meta-analyses (>60 RCTs), 13 systematic reviews, and 4 RCTs that were not included in any of the meta-analyses. Saline irrigation improved symptom scores compared with no treatment (standardized mean difference [SMD], 1.42 [95% CI, 1.01 to 1.84]; a positive SMD indicates improvement). Topical corticosteroid therapy improved overall symptom scores (SMD, -0.46 [95% CI, -0.65 to -0.27]; a negative SMD indicates improvement), improved polyp scores (SMD, -0.73 [95% CI, -1.0 to -0.46]; a negative SMD indicates improvement), and reduced polyp recurrence after surgery (relative risk, 0.59 [95% CI, 0.45 to 0.79]). Systemic corticosteroids and oral doxycycline (both for 3 weeks) reduced polyp size compared with placebo for 3 months after treatment (P < .001). Leukotriene antagonists improved nasal symptoms compared with placebo in patients with nasal polyps (P < .01). Macrolide antibiotic for 3 months was associated with improved QOL at a single time point (24 weeks after therapy) compared with placebo for patients without polyps (SMD, -0.43 [95% CI, -0.82 to -0.05]).


CONCLUSIONS AND RELEVANCE
Evidence supports daily high-volume saline irrigation with topical corticosteroid therapy as a first-line therapy for chronic sinusitis. A short course of systemic corticosteroids (1-3 weeks), short course of doxycycline (3 weeks), or a leukotriene antagonist may be considered in patients with nasal polyps. A prolonged course (3 months) of macrolide antibiotic may be considered for patients without polyps.
Model averaging, optimal inference, and habit formation

Postulating that the brain performs approximate Bayesian inference generates principled and empirically testable models of neuronal function-the subject of much current interest in neuroscience and related disciplines. Current formulations address inference and learning under some assumed and particular model. In reality, organisms are often faced with an additional challenge-that of determining which model or models of their environment are the best for guiding behavior. Bayesian model averaging-which says that an agent should weight the predictions of different models according to their evidence-provides a principled way to solve this problem. Importantly, because model evidence is determined by both the accuracy and complexity of the model, optimal inference requires that these be traded off against one another. This means an agent's behavior should show an equivalent balance. We hypothesize that Bayesian model averaging plays an important role in cognition, given that it is both optimal and realizable within a plausible neuronal architecture. We outline model averaging and how it might be implemented, and then explore a number of implications for brain and behavior. In particular, we propose that model averaging can explain a number of apparently suboptimal phenomena within the framework of approximate (bounded) Bayesian inference, focusing particularly upon the relationship between goal-directed and habitual behavior.
The Role of Oxidative Stress and Lipid Peroxidation in Ventricular Remodeling Induced by Tobacco Smoke Exposure after Myocardial Infarction

OBJECTIVE
To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction.


METHODS
After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses.


RESULTS
Rats in the ETS group showed higher diastolic (C = 1.52 +/- 0.4 mm(2), ETS = 1.95 +/- 0.4 mm(2); p=0.032) and systolic (C = 1.03 +/- 0.3, ETS = 1.36 +/- 0.4 mm(2)/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 +/- 10.1 %, ETS = 19.2 +/- 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 +/- 2.2, ETS = 5.1 +/- 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 +/- 7.6 nmol/mg of protein, ETS = 40.7 +/- 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 +/- 0.1 nmol/g of protein, ETS = 0.9 +/- 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 +/- 0.2 nmol/mg of tissue, ETS = 0.1 +/- 0.1 nmol/mg of tissue; p=0.08).


CONCLUSION
In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular remodeling after myocardial infarction.
Characterization of hadrucalcin, a peptide from Hadrurus gertschi scorpion venom with pharmacological activity on ryanodine receptors.

BACKGROUND AND PURPOSE
Members of the calcin family, presently including imperatoxin A, maurocalcin, opicalcins and hemicalcin, are basic, 33-mer peptide activators of ryanodine receptors (RyRs), the calcium channels of the sarcoplasmic reticulum (SR) that provide the majority of calcium for muscle contraction. Here we describe hadrucalcin, a novel member of this family.


EXPERIMENTAL APPROACH
Hadrucalcin was isolated from the venom of Hadrurus gertschi. Amino acid sequence and mass were determined by Edman degradation and mass spectrometry respectively. A cDNA library was constructed to generate clones for DNA sequence determination. Biological activity of native toxin was confirmed with [(3)H]ryanodine binding, by using SR vesicles from cardiac and skeletal muscle, and with single skeletal (RyR1) and cardiac (RyR2) channels reconstituted in lipid bilayers. Hadrucalcin was applied to intact ventricular myocytes to investigate effects on calcium transients. The secondary structure of hadrucalcin was computer-modelled by using atomic coordinates from maurocalcin, a structurally similar peptide.


KEY RESULTS
Hadrucalcin is distinguished from previously described congeners by two additional amino acids in its primary sequence and the lack of prominent amphipathicity. Hadrucalcin activated RyRs with high affinity (EC(50)= 37 nmol.L(-1)), induced a long-lasting subconductance state on RyR1 and RyR2, and rapidly (lag time approximately 2 s) penetrated ventricular cardiomyocytes, eliciting discharge of internal calcium stores and spontaneous contractions.


CONCLUSIONS AND IMPLICATIONS
Hadrucalcin is a cell-permeant, powerful activator of RyRs, which has translational potential for targeted delivery of drugs to RyR as novel therapeutic intervention in arrhythmogenic disease.
Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.
Face recognition under varying illumination

To eliminate the effects of illumination variation, the conventional approaches firstly produce a compensation-based face image under standard illumination from the input image and then match the image with the face templates in a database. This method is not inapplicable to the input image with large illumination variation. Therefore, a novel method for varying illumination conditions is proposed. Firstly, the quotient image method is improved. Then, the nine basis images of each subject are generated by the improved quotient image method. Thirdly, one new image of each subject under the same lighting conditions with an input image is synthesized by the corresponding basis images. Finally, the synthetic images and the input image are projected to PCA plane to fulfill the recognition task. The experimental results show that the proposed approach can eliminate the effects of illumination variation and have a high recognition rate in the illumination conditions with remarkable changes.
Screening risk-averse agents under moral hazard: single-crossing and the CARA case

Principal-agent models of moral hazard have been developed under the assumption that the principal knows the agent’s risk-aversion. This paper extends the moral hazard model to the case when the agent’s risk-aversion is his private information, so that the model also exhibits adverse selection. We characterize the optimal menu of contracts; while its detailed properties depend on the setting, we show that some of them must hold for all environments. In particular, the power of incentives always decreases with risk-aversion. We also characterize the relationship between the outside option and the optimal contracts. We then apply our results to testing for asymmetric information in insurance markets.
A syntactic approach for aspect based opinion mining

Opinion mining or sentiment analysis is the process of analysing the text about a topic written in a natural language and classify them as positive negative or neutral based on the humans sentiments, emotions, opinions expressed in it. Nowadays, the opinions expressed through reviews are increasing day by day on the web. It is practically impossible to analyse and extract opinions from such huge number of reviews manually. To solve this problem an automated opinion mining approach is needed. This task of automatic opinion mining can be done mainly at three different levels, which are document level, sentence level and aspect level. Most of the previous work is in the field of document or sentence level opinion mining. This paper focus on aspect level opinion mining and propose a new syntactic based approach for it, which uses syntactic dependency, aggregate score of opinion words, SentiWordNet and aspect table together for opinion mining. The experimental work was done on restaurant reviews. The dataset of restaurant reviews was collected from web and tagged manually. The proposed method achieved total accuracy of 78.04% on the annotated test set. The method was also compared with the method, which uses Part-Of-Speech tagger for feature extraction; the obtained results show that the proposed method gives 6% more accuracy than previous one on the annotated test set.
Dysautonomia in the joint hypermobility syndrome.

PURPOSE
Extraarticular manifestations of the joint hypermobility syndrome may include the peripheral nervous system. The purpose of this study was to investigate autonomic function in patients with this syndrome.


METHODS
Forty-eight patients with the joint hypermobility syndrome who fulfilled the 1998 Brighton criteria and 30 healthy control subjects answered a clinical questionnaire designed to evaluate the frequency of complaints related to the autonomic nervous system. Next, 27 patients and 21 controls underwent autonomic evaluation: orthostatic testing, cardiovascular vagal and sympathetic functions, catecholamine levels, and adrenoreceptor responsiveness.


RESULTS
Symptoms related to the autonomic nervous system, such as syncope and presyncope, palpitations, chest discomfort, fatigue, and heat intolerance, were significantly more common among patients. Orthostatic hypotension, postural orthostatic tachycardia syndrome, and uncategorized orthostatic intolerance were found in 78% (21/27) of patients compared with in 10% (2/21) of controls. Patients with the syndrome had a greater mean (+/- SD) drop in systolic blood pressure during hyperventilation than did controls (-11 +/- 7 mm Hg vs. -5 +/- 5 mm Hg, P = 0.02) and a greater increase in systolic blood pressure after a cold pressor test (19 +/- 10 mm Hg vs. 11 +/- 13 mm Hg, P = 0.06). Patients with the syndrome also had evidence of alpha-adrenergic (as assessed by administration of phenylephrine) and beta-adrenergic hyperresponsiveness (as assessed by administration of isoproterenol).


CONCLUSION
The autonomic nervous system-related symptoms of the patients have a pathophysiological basis, which suggests that dysautonomia is an extraarticular manifestation in the joint hypermobility syndrome.
Intersphincteric resection in patients with very low rectal cancer: a review of the Japanese experience.

PURPOSE
This study was designed to evaluate the feasibility and oncologic and functional outcomes of intersphincteric resection for very low rectal cancer.


METHODS
A feasibility study was performed using 213 specimens from abdominoperineal resections of rectal cancer. Oncologic and functional outcomes were investigated in 228 patients with rectal cancer located <5 cm from the anal verge who underwent intersphincteric resection at seven institutions in Japan between 1995 and 2004.


RESULTS
Curative operations were accomplished by intersphincteric resection in 86 percent of patients who underwent abdominoperineal resection. Complete microscopic curative surgery was achieved by intersphincteric resection in 225 of 228 patients. Morbidity was 24 percent, and mortality was 0.4 percent. During the median observation time of 41 months, rate of local recurrence was 5.8 percent at three years, and five-year overall and disease-free survival rates were 91.9 percent and 83.2 percent, respectively. In 181 patients who received stoma closure, 68 percent displayed good continence, and only 7 percent showed worsened continence at 24 months after stoma closure. Patients with total intersphincteric resection displayed significantly worse continence than patients with partial or subtotal resection.


CONCLUSIONS
Curability with intersphincteric resection was verified histologically, and acceptable oncologic and functional outcomes were obtained by using these procedures in patients with very low rectal cancer. However, information on potential functional adverse effects after intersphincteric resection should be provided to patients preoperatively.