Miracle-dz/UniFAR-FTUs huggingface dataset:
Lin28 Induces Epithelial-to-Mesenchymal Transition and Stemness via Downregulation of Let-7a in Breast Cancer Cells

The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.
Evolutionary dynamics of a food web with recursive branching and extinction

A dynamic systems approach to evolutionary branching and its development in an artificial food web is presented. Predator-prey interaction among trophic species with two traits generates a variety of evolutionary branching patterns, depending on interaction strengths and mutation rates. Studying branching patterns in a phenotypic space reveals three branching patterns: prey-bifurcation, predator-bifurcation, and net-bifurcation. In particular, a complex food web network emerges through net-bifurcation. A relationship between biomass and the number of species is analysed by changing the interaction strength. We report that the branching and extinction rates of trophic species reaches a maximum when the number of species, but not the entire biomass, reaches a maximum.
User interface model discovery: towards a generic approach

UI model discovery is a lightweight formal method in which a model of an interactive system is automatically discovered by exploring the system's state space, simulating the actions of a user; such models are then amenable to automatic analysis targetting structural usability concerns. This paper specifies UI model discovery in some detail, providing a formal, generic and language-neutral API and discovery algorithm. The technique has been implemented in prototype systems on several programming platforms, yielding valuable usability insights. The API described here supports further development of these ideas in a systematic manner.
PI3K/Akt/mTOR inhibitors in breast cancer

Activation of the phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is common in breast cancer. There is preclinical data to support inhibition of the pathway, and phase I to III trials involving inhibitors of the pathway have been or are being conducted in solid tumors and breast cancer. Everolimus, an mTOR inhibitor, is currently approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this review, we summarise the efficacy and toxicity findings from the randomised clinical trials, with simplified guidelines on the management of potential adverse effects. Education of healthcare professionals and patients is critical for safety and compliance. While there is some clinical evidence of activity of mTOR inhibition in HR-positive and HER2-positive breast cancers, the benefits may be more pronounced in selected subsets rather than in the overall population. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the PI3K/Akt/mTOR (PAM) pathway.
Granulocyte-Macrophage Colony-Stimulating Factor Enhancer Activation Requires Cooperation between NFAT and AP-1 Elements and Is Associated with Extensive Nucleosome Reorganization

ABSTRACT The human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene is activated by an NFAT-dependent enhancer forming an inducible DNase I hypersensitive (DH) site. The enhancer core comprising the DH site contains the GM330 and GM420 elements that bind NFAT and AP-1 cooperatively. Here we demonstrate that both elements are essential for enhancer activity and that Sp1 and AML1 sites in the enhancer become occupied in vivo only after activation. Chromatin structure analysis revealed that the GM-CSF enhancer core elements are divided between two adjacent nucleosomes that become destabilized and highly accessible after activation. Inducible chromatin reorganization was not restricted to the enhancer core but extended across a 3-kb domain of mobilized nucleosomes, within which the nucleosome repeat length was compressed from approximately 185 to 150 bp. The GM420 element is a high-affinity site that binds NFAT independently of AP-1 but depends on the linked AP-1 site for enhancer function. Nevertheless, just the NFAT motif from the GM420 element was sufficient to form a DH site within chromatin even in the absence of the AP-1 site. Hence, NFAT has the potential to cooperate with other transcription factors by promoting chromatin remodelling and increasing accessibility at inducible regulatory elements.
Retention or loss of v-mil sequences after propagation of MH2 virus in vivo or in vitro

During propagation of the defective avian retrovirus MH2 in the presence of replication-competent helper virus, deletion of portions of the viral genome occurred frequently. After transformation of quail cells in vitro, v-mil sequences were lost, leading to populations of MH2 viruses which were highly deficient for mil gene expression but which could transform macrophage and fibroblast cells in vitro with high efficiency. In contrast, after induction of tumors in quail with mil-deficient MH2 viral stocks, a majority of the tumor DNAs contained mil+ proviruses, suggesting that there is selection for retention of the v-mil gene in vivo and that the mil protein may play a role in the oncogenicity of MH2 virus. We also isolated MH2-transformed cell lines which contained deleted proviruses arising from packaging and subsequent integration of the subgenomic v-myc-encoding mRNA. Some of these cell lines produced viruses which encoded abnormal v-myc proteins and had altered in vitro transforming properties. These altered phenotypes may be caused by mutations within the v-myc gene.
Predictors of Death during Tuberculosis Treatment in TB/HIV Co-Infected Patients in Malaysia

Background Mortality among TB/HIV co-infected patients is still high particularly in developing countries. This study aimed to determine the predictors of death in TB/HIV co-infected patients during TB treatment. Methods We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all newly registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in the Klang Valley between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes and survival. We analysed using Kaplan-Meier and conducted multivariate Cox proportional hazards analysis to identify predictors of death during TB treatment in TB/HIV co-infected patients. Results Of the 227 patients studied, 53 (23.3%) had died at the end of the study with 40% of deaths within two months of TB diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were 90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73-11.64), CD4 T-lymphocytes count < 200 cells/µl (aHR 3.89; 95% CI 1.20-12.63), three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per 103 total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20) Conclusion TB/HIV co-infected patients had a high case fatality rate during TB treatment. Initiation of antiretroviral therapy in these patients can improve survival by restoring immune function and preventing opportunistic infections.
A Transition-Based System for Joint Part-of-Speech Tagging and Labeled Non-Projective Dependency Parsing

Most current dependency parsers presuppose that input words have been morphologically disambiguated using a part-of-speech tagger before parsing begins. We present a transition-based system for joint part-of-speech tagging and labeled dependency parsing with non-projective trees. Experimental evaluation on Chinese, Czech, English and German shows consistent improvements in both tagging and parsing accuracy when compared to a pipeline system, which lead to improved state-of-the-art results for all languages.
The Newcastle protocols 2008: an update on head-up tilt table testing and the management of vasovagal syncope and related disorders

Since their publication in 2000, the Newcastle protocols1 on head-up tilt testing in the diagnosis of vasovagal syncope and related disorders have provided a succinct and practical guide for those setting up and managing syncope services incorporating the investigation and management of neurally mediated disorders. In the intervening seven years our protocols have changed in line with published evidence on new methodologies and management strategies and our own clinical experience (with more than 1000 new and 3000 review patients seen each year at our specialist syncope facility), so the time is ripe for a fresh approach. Much of this information is available in a number of important papers on syncope management2–4 and pacing indications5 6; while comprehensive, these guidelines are also lengthy and inclusive of competing methodologies. They are therefore less accessible for those needing a more prescriptive and pragmatic view. The Newcastle protocols 2008 presented below provide such a view. Since these protocols reflect current clinical practice, an exhaustive review of the evidence base for the various methodologies presented will not be attempted—the reader should consult the more detailed papers referenced if this is required.2–6 Similarly some prior knowledge of the subject matter is assumed, in particular the differentiation between syncope and non-syncopal loss of consciousness as well as the diagnostic process leading to head-up tilt table testing.2 3 The protocols are designed for adults with syncope (defined as transient loss of consciousness with loss of postural tone and spontaneous and complete recovery), with no upper limit on age. The Newcastle protocols 2008 are intended to complement rather than reproduce the originals, so only new information will be presented, occasionally with a summarised version of the old to aid clarity. Still-valid detailed prior information will be referenced to the …
Understanding Farmers’ Perceptions and Adaptations to Precipitation and Temperature Variability: Evidence from Northern Iran

Precipitation and temperature variability present significant agricultural risks worldwide. Northern Iran’s agriculture mainly depends on paddy fields, which are directly affected by precipitation and temperature variability. The main aim of this study is to explore farmers’ attitudes towards precipitation and temperature variability and their adaptation strategies in paddy fields in a typical agricultural province in northern Iran. Primary survey data were collected from a sample of 382 paddy farmers of Rasht County in Guilan Province. Data have been analyzed using both summary statistics and bivariate analysis (Pearson, Spearman, and Eta correlation coefficients). Empirical findings reveal that most paddy farmers had experienced precipitation and temperature variability and were taking measures to reduce its negative impacts on their crops. Results also indicate that farm size and household income influence farmers’ perception to precipitation and temperature variability, while availability of water resources also influence farmers’ adaptation decisions.
A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated With BRAF Mutations.

IMPORTANCE Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included. MAIN OUTCOMES AND MEASURES BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined. RESULTS A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models. CONCLUSIONS AND RELEVANCE Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.
Variational posterior distribution approximation in bayesian emission tomography reconstruction using a gamma mixture prior

Following the Bayesian framework we propose a method to reconstruct emission tomography images which uses gamma mixture prior and variational methods to approximate the posterior distribution of the unknown parameters and image instead of estimating them by using the Evidence Analysis or alternating between the estimation of parameters and image (Iterated Conditional Mode (ICM)) approach. By analyzing the posterior distribution approximation we can examine the quality of the proposed estimates. The method is tested on real Single Positron Emission Tomography (SPECT) images.
Using electroencephalography and subjective self-assessment to measure the influence of quality variations in cloud gaming

Subjective self-assessment is a frequently used method when it comes to Quality of Experience assessment in general. If correctly used a variety of scales can be applied to assess the quality of cloud gaming for different constructs such as experienced quality or flow. Besides self-assessment, physiological correlates are a promising method to measure the influence of cloud gaming quality on the player without the interruption introduced by the rating task. We present subjective and physiological results and lessons learned from a laboratory study in which 32 participants played a first person shooter game in a cloud gaming setup with varying levels of video quality caused by different video compression bitrates. We found that the video quality influenced the perceived quality, player experience, the valence rating, and the alpha frequency band power. It is shown that 1) subjective methods assess the quality variation and 2) physiological measures capture the influence on the player in terms of a reduced cognitive state. Taken together, test set-ups will benefit from a mixed methods approach in cloud gaming QoE testing.
Oil Price Shocks, Income, and Democracy

Abstract We examine the effect of oil price fluctuations on democratic institutions over the 1960–2007 period. We also exploit the very persistent response of income to oil price fluctuations to study the effect of persistent (oil-price-driven) income shocks on democracy. Our results indicate that countries with greater net oil exports over GDP see improvements in democratic institutions following upturns in international oil prices. We estimate that a 1 percentage point increase in per capita GDP growth due to a positive oil price shock increases the Polity democracy score by around 0.2 percentage points on impact and by around 2 percentage points in the long run. The effect on the probability of a democratic transition is around 0.4 percentage points.
Bevacizumab beyond disease progression for advanced non–small cell lung cancer: Does persistence have its rewards?

In selecting cancer treatments, as in life, sometimes it pays to be persistent. But not knowing when to quit carries its own hazards as well, particularly in the face of potentially diminishing benefits, increasing toxicities, and significant costs. These issues become even more relevant as new treatment options emerge with more favourable toxicity profiles, enabling long term treatment without the cumulative toxicities of chemotherapy. Whether or not there is benefit to continuing a targeted drug past progression depends on a host of factors, and likely varies by drug and tumor type. For example, does the tumor retain at least some dependence on a target blocked by the drug, or does the resistance mechanism completely bypass the target? Does stopping the drug induce a “rebound” effect that could accelerate tumor progression when the drug is stopped?
Measured Mass-Loss Rates of Solar-like Stars as a Function of Age and Activity

Collisions between the winds of solar-like stars and the local interstellar medium result in a population of hot hydrogen gas surrounding these stars. Absorption from this hot H I can be detected in high-resolution Lyα spectra of these stars from the Hubble Space Telescope. The amount of absorption can be used as a diagnostic for the stellar mass-loss rate. We present new mass-loss rate measurements derived in this fashion for four stars (ϵ Eri, 61 Cyg A, 36 Oph AB, and 40 Eri A). Combining these measurements with others, we study how mass loss varies with stellar activity. We find that for the solar-like GK dwarfs, the mass loss per unit surface area is correlated with X-ray surface flux. Fitting a power law to this relation yields ∝ F. The active M dwarf Proxima Cen and the very active RS CVn system λ And appear to be inconsistent with this relation. Since activity is known to decrease with age, the above power-law relation for solar-like stars suggests that mass loss decreases with time. We infer a power-law relation of ∝ t-2.00±0.52. This suggests that the solar wind may have been as much as 1000 times more massive in the distant past, which may have had important ramifications for the history of planetary atmospheres in our solar system, that of Mars in particular.
Invited Commentary Invited Commentary: An Ingenious Approach to Examining the Relationship Between Maternal Stress and Offspring Health?

The potentially deleterious effects on offspring health of excess maternal stress in pregnancy are important to understand—both whether observed associations are causal and through what mechanisms their effects may exert an influence. In this issue of the Journal, Räikkönen et al. (Am J Epidemiol. 2017;185(5):317–328) provide an ingenious test of a potential pathway through which maternal stress may influence offspring development. Licorice consumption is known to disrupt the ability of the placental enzyme 11β-hydroxysteroid dehydrogenase type 2 to inactivate cortisol before it reaches the fetus, leading to higher levels of cortisol exposure. Higher levels of cortisol exposure are also hypothesized to underlie the mechanism through which maternal stress may disrupt fetal development. Thus licorice consumption may serve, in some ways, to mimic maternal stress. The authors report associations between heavy licorice consumption during pregnancy and a wide range of offspring outcomes, including changes in pubertal timing, intelligence quotient, and mental health. In our view, these results should be considered preliminary; more work needs to be completed to determine the relationship of prenatal licorice consumption to these outcomes. Nonetheless, these intriguing and suggestive results demonstrate that this line of work should be given high priority, and they set the stage for additional research moving forward.
Exploiting Salient Patterns for Question Detection and Question Retrieval in Community-based Question Answering

Question detection serves great purposes in the cQA question retrieval task. While detecting questions in standard language data corpus is relatively easy, it becomes a great challenge for online content. Online questions are usually long and informal, and standard features such as question mark or 5W1H words are likely to be absent. In this paper, we explore question characteristics in cQA services, and propose an automated approach to detect question sentences based on lexical and syntactic features. Our model is capable of handling informal online languages. The empirical evaluation results further demonstrate that our model significantly outperforms traditional methods in detecting online question sentences, and it considerably boosts the question retrieval performance in cQA.
Controlling Selection Bias in Causal Inference

Selection bias, caused by preferential exclusion of units (or samples) from the data, is a major obstacle to valid causal inferences, for it cannot be removed or even detected by randomized experiments. This paper highlights several graphical and algebraic methods capable of mitigating and sometimes eliminating this bias. These nonparametric methods generalize and improve previously reported results, and identify the type of knowledge that need to be available for reasoning in the presence of selection bias
Herpes simplex virus‐based vectors

Herpes simplex virus (HSV)‐based vectors have primarily been developed for neuronal gene delivery, taking advantage of the virus' natural neurotropism. Two types of vector are available: replication defective viruses, whose cytotoxicity has been abolished by deleting viral gene products, and amplicon vectors, which are plasmids packaged into HSV particles with the aid of a helper virus. In this review I discuss how the cytotoxicity of the wild‐type virus has been abolished, the progress which has been made toward defining promoter elements capable of directing long‐term transgene expression form the latent viral genome and some of the potential clinical uses of these versatile vectors.