Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology

Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (resistance ratio: 0.33). HCT-116 colon carcinoma p53-/- knockout cells were 7.16-fold resistant toward As2O3 compared to wild-type cells. Forty genes determining cellular responsiveness to As2O3 were identified by microarray and COMPARE analyses in 58 cell lines of the NCI panel. Hierarchical cluster analysis-based heat mapping revealed significant differences between As2O3 sensitive cell lines and resistant cell lines with p-value: 1.86 × 10-5. The genes were subjected to Galaxy Cistrome gene promoter transcription factor analysis to predict the binding of transcription factors. We have exemplarily chosen NF-kB and AP-1, and indeed As2O3 dose-dependently inhibited the promoter activity of these two transcription factors in reporter cell lines. Furthermore, the genes identified here and those published in the literature were assembled and subjected to Ingenuity Pathway Analysis for comprehensive network pharmacological approaches that included all known factors of resistance of tumor cells to As2O3. In addition to pathways related to the anticancer effects of As2O3, several neurological pathways were identified. As arsenic is well-known to exert neurotoxicity, these pathways might account for neurological side effects. In conclusion, the activity of As2O3 is not restricted to acute promyelocytic leukemia. In addition to PML/RARA, numerous other genes belonging to diverse functional classes may also contribute to its cytotoxicity. Network pharmacology is suited to unravel the multifactorial modes of action of As2O3.
Outsourcing Expert Services by State Transportation Departments

Privatization has increasingly become a policy option for government agencies struggling to meet rising demands for services but with fewer resources. In the transportation arena, many state departments of transportation (DOTs) have privatized by outsourcing highway functions to the private sector. But the outsourcing of technical and expert services such as those related to the design and construction of highway infrastructure may result in a smaller or less knowledgeable DOT workforce that is unable to perform the necessary contract management to ensure the quality of the work done by contractors. We posit an outsourcing process in which DOTs respond to the combination of increased demand for highway services and growing workforce constraints by contracting out much of the work formerly performed by in-house personnel. This, in turn, can produce perceptions of quality problems regarding the outsourced work and a subsequent expansion of the workforce. We examine the extent to which different highway-related tasks are being outsourced, the effect of workforce and employment factors on outsourcing, the perceptions of highway officials regarding the impact of outsourcing on cost-effectiveness and the service quality of the outsourced work, and subsequent employment levels.
Are Isolated and Complex Fiber Supplements Good Choices for Weight Management? A Systematic Review.

BACKGROUND Previous trials have reported beneficial effects of isolated and complex fiber supplements in obesity treatment. However, recommending fiber supplements in obese subjects remains controversial. To the best of our knowledge, no systematic review has updated the data on the effects of fiber supplements on obesity since 2010 and the need exists for a systematic review on this topic. Accordingly, a systematic review was undertaken to summarize the efficacy of different types of fiber supplements as a complementary treatment for weight management. METHODS We searched PubMed, Scopus, Cochrane Library and Google Scholar between January 2010 to August 2016 with no language restriction. Considering the inclusion/exclusion criteria and quality assessment score, finally 17 clinical trials met the eligibility criteria and were included. RESULTS The present study indicated that the efficacy of various fiber supplements on losing weight is variable. Several mechanisms related to physicochemical properties of fibers such as solubility, fermentability and viscosity rates can be involved in their anti-obesity effects. Dextrin, Mannan (gum Arabic) and pectin-rich fiber (lupin kernel) with no dietary interventions indicated a reduction in body weight and energy intake, while from clinical point of view, their effects were not considerable. CONCLUSION Overall, findings indicated that the efficacy of fiber supplements on obesity management is dependent on their contents and physicochemical properties. It seems that fiber supplements with no weight-loss interventions did not have considerable antiobesity effects. However, due to limited studies on each type of fiber, findings should be declared by caution. Additional research is needed on comparison of different fiber supplements in similar conditions to clarify the best type and dosage of fiber supplement as a complementary therapy in obesity management.
Pictorial cigarette pack warnings increase quitting: a comment on Kok et al.

In this issue of Health Psychology Review, Kok et al. (2018) argue that pictorial cigarette pack warnings are ineffective. Evidence published recently, however, shows that pictorial warnings do decrease smoking which is a notably deadly behavior (Brewer et al., 2016; Noar et al., 2017). Our commentary summarizes evidence of pictorial warnings' effectiveness and comments on other aspects of the article.
A Twofold Siamese Network for Real-Time Object Tracking

Observing that Semantic features learned in an image classification task and Appearance features learned in a similarity matching task complement each other, we build a twofold Siamese network, named SA-Siam, for real-time object tracking. SA-Siam is composed of a semantic branch and an appearance branch. Each branch is a similaritylearning Siamese network. An important design choice in SA-Siam is to separately train the two branches to keep the heterogeneity of the two types of features. In addition, we propose a channel attention mechanism for the semantic branch. Channel-wise weights are computed according to the channel activations around the target position. While the inherited architecture from SiamFC [3] allows our tracker to operate beyond real-time, the twofold design and the attention mechanism significantly improve the tracking performance. The proposed SA-Siam outperforms all other real-time trackers by a large margin on OTB-2013/50/100 benchmarks.
Quadrupole Splittings of Alkali NMR Signals in Decylammoniumchloride Mesophases

In lyotropic mesophases of decylammoniumchloride the NMR signals of the alkali nuclei 6Li, 7Li, 23Na, 39K, 85Rb, 87Rb and 133Cs solubilized in these mesophases have been observed. The linewidths of the signals are comparable with the linewidths in aqueous solutions. Apart from 6Li and 39K for all other alkali nuclei in the mesophases first-order quadrupole splitted spectra have been observed. For the rubidium isotopes 85Rb and 87Rb a ratio of the quadrupole splitting of 2.01 ± 0.05 has been determined. Further the chemical shifts of the solubilized alkali nuclei relative to infinitely diluted aqueous solutions have been measured.
NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer

Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor type that is typically metastatic upon diagnosis. We have a poor understanding of the factors that control SCLC progression and metastasis. TheNFIB transcription factor is frequently amplified in mouse models of SCLC, but clear evidence that NFIB promotes SCLC in vivo is lacking. We report that in mouse models, Nfib amplifications are far more frequent in liver metastases over primary SCLC, suggesting roles in tumor progression/metastasis. Overexpression of Nfib in a sensitized mouse model led to acceleration of SCLC, indicating that Nfib functions as a bona fide oncogene. Suppression of Nfib expression in cell lines derived from the doxycycline-inducible Rb/p53/TET-Nfib model led to increased apoptosis and suppression of proliferation. Transcriptional analysis revealed that Nfib regulates the expression of genes related to axon guidance, focal adhesion and extracellular matrix-receptor interactions. These data indicate that Nfib is a potent oncogene in SCLC, and the enrichment of Nfib amplifications in liver metastases over primary SCLC points to Nfib as a candidate driver of SCLC metastasis.
Errors in Mammography Cannot be Solved Through Technology Alone

Mammography has been the frontline screening tool for breast cancer for decades. However, high error rates in the form of false negatives (FNs) and false positives (FPs) have persisted despite technological improvements. Radiologists still miss between 10% and 30% of cancers while 80% of woman recalled for additional views have normal outcomes, with 40% of biopsied lesions being benign. Research show that the majority of cancers missed is actually visible and looked at, but either go unnoticed or are deemed to be benign. Causal agents for these errors include human related characteristics resulting in contributory search, perception and decision-making behaviours. Technical, patient and lesion factors are also important relating to positioning, compression, patient size, breast density and presence of breast implants as well as the nature and subtype of the cancer itself, where features such as architectural distortion and triple-negative cancers remain challenging to detect on screening. A better understanding of these causal agents as well as the adoption of technological and educational interventions, which audits reader performance and provide immediate perceptual feedback, should help. This paper reviews the current status of our knowledge around error rates in mammography and explores the factors impacting it. It also presents potential solutions for maximizing diagnostic efficacy thus benefiting the millions of women who undergo this procedure each year.
Please stay with me! An empirical investigation on hedonic IS continuance model for social network games

It has long been a challenge for online game providers that, after playing a game for a certain period of time, online game players frequently switch to alternative games without much hesitation. Current IS continuance theories, that are mainly developed to interpret user continuance of general utilitarian IS, are ineffective to interpret user continuance of hedonic IS. In this study, based on the uses and gratifications theory, a hedonic IS continuance model is developed by incorporating three sorts of gratifications, namely hedonic gratification (enjoyment, fantasy and escapism), social gratification (social interaction and social presence) and utilitarian gratification (achievement and self-presentation). Age and gender are the moderating factors in the model. Based on 3919 validated respondents, the research model is assessed while a number of interesting findings are reported.
Accurate Simulation of Parametrically Excited Micromirrors via Direct Computation of the Electrostatic Stiffness

Electrostatically actuated torsional micromirrors are key elements in Micro-Opto-Electro- Mechanical-Systems. When forced by means of in-plane comb-fingers, the dynamics of the main torsional response is known to be strongly non-linear and governed by parametric resonance. Here, in order to also trace unstable branches of the mirror response, we implement a simplified continuation method with arc-length control and propose an innovative technique based on Finite Elements and the concepts of material derivative in order to compute the electrostatic stiffness; i.e., the derivative of the torque with respect to the torsional angle, as required by the continuation approach.
Discretionary food and beverage consumption and its association with demographic characteristics, weight status, and fruit and vegetable intakes in Australian adults

Abstract Objective Excessive consumption of discretionary foods/beverages in the Australian population has been identified, increasing the risk of obesity and chronic disease. The present study aimed to examine the associations between demographic, anthropometric and dietary factors and the consumption of discretionary foods, discretionary beverages and discretionary foods/beverages combined. Design Discretionary food/beverage consumption reported in two 24 h recalls was analysed, stratified by gender, age, socio-economic status, country of birth, BMI, waist circumference, and fruit and vegetable intakes. Setting 2011–12 National Nutrition and Physical Activity Survey. Subjects Australian adults (n 7873) aged 19 years or above. Results Mean discretionary food and beverage consumption was 631 g (28 % by weight from foods; 72 % from beverages), providing 2721 kJ of energy intake (72 % from foods; 28 % from beverages). Total discretionary food/beverage consumption was higher in younger age groups (P<0·001), those in lower socio-economic categories (P<0·001), those born in Australia (P<0·001), those with higher BMI (P<0·001) and those with lower fruit (P<0·001) or vegetable intake (P<0·001). Discretionary beverage consumption (β=6·6, P<0·001) was more strongly associated with BMI than discretionary food consumption (β=0·5, P=0·01). Conclusions Total discretionary food/beverage consumption as well as discretionary foods alone and discretionary beverages alone were associated with BMI in Australian adults. In addition, high intakes were associated with younger age, lower socio-economic status, and lower consumption of fruit and vegetables.
Low Cholesterol is Associated with Mortality from Cardiovascular Diseases: A Dynamic Cohort Study in Korean Adults

This study was conducted to evaluate the association of single serum total cholesterol (TC) measurement with cardiovascular diseases (CVD) deaths in Korean adults. The study subjects were taken from the multi-site collaborative dynamic prospective cohort for epidemiologic investigation on cancer risk in residents nearby nuclear power plants in Korea. A total of 12,740 adults aged 40 to 69 yr who underwent a mass screening examination were followed up from 1993 to 2008. Occurring CVD deaths were confirmed by the death certificates in the National Statistical Office, Korea. Groups with the lowest group having TC < 160 mg/dL as well as the highest group having >= 240 mg/dL were associated with higher CVD mortality in Cox proportional hazards analysis adjusting for age, sex, smoking and drinking status, body mass index, level of blood pressure, triglyceride and high density lipoprotein cholesterol. The distribution of adjusted hazard ratios showed the U-shaped curve. Based on the results of this study, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk in Korean adults.
Retinal ganglion cell/inner plexiform layer thickness in patients with Parkinson's disease.

Introduction: The aim of the paper was to analyze the changes in the macular ganglion cell layer and inner plexiform layer (GCL-IPL) thickness in patients with Parkinson's disease. Material and methods: The study enrolled 46 patients with established diagnosis of Parkinson's disease and 46 healthy subjects. Both groups were age- and gender-matched. An OCT protocol, namely standardized Ganglion Cell Analysis algorithm was used to measure the thickness of the macular GCL-IPL layer. The average, minimum, and six sectoral (superotemporal, superior, superonasal, inferonasal, inferior, inferotemporal) GCL-IPL thicknesses were measured from the elliptical annulus centered on the fovea. Results: The mean value of the clinical severity of Parkinson's disease was between 2 and 3, according to the Hoehn and Yahr scale. Statistically significant thinning of the GCL-IPL layer was registered in average and minimum GCL-IPL thickness, as well as in the sectoral layer thicknesses in patients with Parkinson's disease in comparison to the controls. There was no correlation between structural changes in the retina and disease duration or severity. A statistically significant difference in thickness between the different stages of the disease was registered only in the inferior sector. Conclusions: Parkinson's disease is accompanied by thinning of the GCL-IPL complex of macula even in the earliest stages. This may indicate a possible retinal dopaminergic neurodegeneration. There is no correlation between duration or severity of Parkinson's disease with thinning of the GCL-IPL complex.
Point: Incident Exposures, Prevalent Exposures, and Causal Inference: Does Limiting Studies to Persons Who Are Followed From First Exposure Onward Damage Epidemiology?

The idea that epidemiologic studies should start from first exposure onward has been advocated in the past few years. The study of incident exposures is contrasted with studies of prevalent exposures in which follow-up may commence after first exposure. The former approach is seen as a hallmark of a good study and necessary for causal inference. We argue that studying incident exposures may be necessary in some situations, but it is not always necessary and is not the preferred option in many instances. Conducting a study involves decisions as to which person-time experience should be included. Although studies of prevalent exposures involve left truncation (missingness on the left), studies of incident exposures may involve right censoring (missingness on the right) and therefore may not be able to assess the long-term effects of exposure. These considerations have consequences for studies of dynamic (open) populations that involve a mixture of prevalent and incident exposures. We argue that studies with prevalent exposures will remain a necessity for epidemiology. The purpose of this paper is to restore the balance between the emphasis on first exposure cohorts and the richness of epidemiologic information obtained when studying prevalent exposures.
Unsupervised Learning of Geometry with Edge-aware Depth-Normal Consistency

Learning to reconstruct depths from a single image by watching unlabeled videos via deep convolutional network (DCN) is attracting significant attention in recent years, e.g. (Zhou et al. 2017). In this paper, we propose to use surface normal representation for unsupervised depth estimation framework. Our estimated depths are constrained to be compatible with predicted normals, yielding more robust geometry results. Specifically, we formulate an edge-aware depth-normal consistency term, and solve it by constructing a depth-to-normal layer and a normal-to-depth layer inside of the DCN. The depth-to-normal layer takes estimated depths as input, and computes normal directions using cross production based on neighboring pixels. Then given the estimated normals, the normal-to-depth layer outputs a regularized depth map through local planar smoothness. Both layers are computed with awareness of edges inside the image to help address the issue of depth/normal discontinuity and preserve sharp edges. Finally, to train the network, we apply the photometric error and gradient smoothness to supervise both depth and normal predictions. We conducted experiments on both outdoor (KITTI) and indoor (NYUv2) datasets, and showed that our algorithm vastly outperforms state-of-the-art, which demonstrates the benefits of our approach.
Circulating magnesium and cardiovascular events.

In their systematic review and meta-analysis of prospective studies, Del Gobbo et al (1) showed an inverse association of magnesium concentrations with the incidence of cardiovascular disease, including fatal and nonfatal ischemic heart disease (IHD). Yet, another recent meta-analysis (2) has reported a beneficial effect of dietary magnesium on cardiovascular disease mortality among women but not among men. However, the meta-analysis by Del Gobbo et al (1) went one step further by analyzing circulating magnesium, which may suggest the key mechanism of the whole issue. All of the studies included in the meta-analysis by Del Gobbo et al (1) that investigated magnesium in women, either by dietary intake or by circulating concentrations, showed a significant protective effect against IHD incidents (3–5). Among studies that reported strictly on circulating magnesium in women, Chiuve et al (4) showed an inverse association with sudden cardiac death, whereas Liao et al (3) reported a trend toward the decreased risk of IHD. Circulating magnesium is directly regulated by renal function (6). On the contrary, dietary magnesium is mostly associated with individual nutrition and dietary habits. Importantly, there is a low correlation between dietary intake and circulating magnesium concentrations. There are reasons why we should distinguish between circulating magnesium concentrations and dietary magnesium and also separate men from women. Prolonged corrected QT (QTc) interval is associated with an increased risk of potentially fatal ventricular tachyarrhythmias (7–13). Intravenous magnesium has been used for treatment and prevention of ventricular tachycardia (8, 11), ventricular fibrillation (10, 13), and polymorphic ventricular tachycardia (7, 12). Because QTc prolongation is more often present in women, we suggested that the beneficial effect of magnesium could be more pronounced in female patients (14). Pathophysiologic mechanisms may include antagonism at the Land T-type calcium channels (15), membrane stabilization (16), reduced frequency of ventricular ectopic beats (17, 18), and conversion to sinus rhythm (7, 8, 10, 19, 20). Accordingly, there is a compelling evidence of benefit from intravenous magnesium application, and so the effect of the circulating magnesium concentration could be substantial for its cardiovascular effects. The facts that intravenous magnesium is effective against ventricular tachyarrhythmias through mechanisms which include prolongation of the QT interval, and that QTc interval is more often prolonged in women could underlie a better antiarrhythmic protection in women than in men. Perhaps Del Gobbo et al could separate the effect of circulating magnesium in men and women and provide the pooled results. The problem of a low correlation between dietary and circulating magnesium must be accounted for in future research. Neither of the authors declared a conflict of interest.