Miracle-dz/UniFAR-FTUs huggingface dataset:
Extravascular Blood Augments Myogenic Constriction of Cerebral Arterioles: Implications for Hemorrhage‐Induced Vasospasm

Background Subarachnoid hemorrhage is a serious clinical condition that impairs local cerebral blood flow perfusion and consequently initiates neuronal dysfunction. Pressure‐sensitive myogenic vasomotor regulation is an important mechanism involved in the regulation of cerebral blood flow. We hypothesized that extravascular hemolyzed blood enhances arteriolar myogenic constriction, which in vivo may contribute to the reduction of local cerebral blood flow after subarachnoid hemorrhage. Methods and Results Arterioles isolated from the middle cerebral artery (MCA arterioles) of mice were cannulated in a perfusion chamber. Arteriolar diameters in response to step increases in intraluminal pressure (20–120 mm Hg) were measured in various experimental conditions. In response to increases in intraluminal pressure, all MCA arterioles exhibited myogenic vasoconstrictions. Compared with controls, the pressure‐induced constriction was significantly enhanced in arterioles (in vitro) exposed to extravascular hemolyzed blood or different concentrations of extracellular erythrocyte lysate (1%, 10%, and 20%) for different exposure durations (1–6 hours). The magnitude of enhancement was proportional to the lysate concentration and exposure duration. In in vivo experiments, 10 μL of autologous blood lysate were injected into the mouse subarachnoid space on the surface of the left MCA. Two hours later, MCA arterioles were isolated and left MCA arterioles displayed enhanced myogenic responses compared with the right MCA. The enhanced myogenic response was prevented by scavenge of superoxide in both in vitro and in vivo experiments. Conclusions Extravascular hemolyzed blood, perhaps by promoting vascular production of superoxide, augments myogenic constriction of cerebral arterioles, which plays a crucial role in the subarachnoid hemorrhage–induced cerebral ischemia.
Self-Reporting of Adverse Drug Reactions in Iraqi Hospitals: Patient’s Perspectives

Background: Adverse drug reactions (ADRs) represent the important cause of morbidity and mortality that affect patients using drugs. Previous studies have clarified the knowledge and attitude toward ADRs reporting among healthcare providers, while studies toward awareness of patients are limited. Aim and Objective: To evaluate knowledge and attitude toward ADRs reporting among patients visiting general hospitals in Baghdad City. Methods: This observational study was conducted on randomly selected 300 patients at the out-patient setting of general hospitals in Baghdad. Demographic characteristics of participants were documented and questionnaire regarding knowledge and perceptions was given to fill up, and the data were analyzed using descriptive statistics. Results: Demographic analysis showed that 55% of patients were males, 62% of them were from rural areas, and only 34% were college graduates. Regarding knowledge about ADRs, 73.3% patients were aware about ADRs and 37% had experienced ADRs in past. None of the respondents were aware of ADR reporting center. Regarding perceptions toward ADR, 84.2% agreed to report ADR in future and 90% respondents believed that ADR reporting may strengthen the patient safety. According to 61% of patients, patient education program is the best way to educate them regarding ADR. Conclusion: Educational interventions are highly recommended to improve awareness among patients regarding the validity of ADRs reporting.
The Nem1/Spo7–Pah1/lipin axis is required for autophagy induction after TORC1 inactivation

Autophagy is a process that requires intense membrane remodeling and consumption. The nutrient‐responsive TORC1 (target of rapamycin complex 1) kinase regulates autophagy. However, how TORC1 controls autophagy via lipid/membrane biogenesis is unknown. TORC1 regulates the function of yeast phosphatidate phosphatase lipin Pah1 via the Nem1/Spo7 phosphatase complex. Here, we show that the Nem1/Spo7–Pah1 axis is required for autophagy induction after TORC1 inactivation and survival during starvation. Furthermore, this axis was critical for nucleophagy (both micronucleophagy and macronucleophagy) and was required for proper localization of micronucleophagy factor Nvj1 and macronucleophagy receptor Atg39. This study indicated that the Nem1/Spo7–Pah1 axis controlled by TORC1 is a critical branch for autophagy induction in nutrient starvation conditions.
Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells

Immune-aging is associated with perturbed immune responses in the elderly. CD161-expressing T cells, i.e., the previously described subsets of CD161+ CD4+ T cells, CD161high CD8+ T cells, and CD161int CD8+ T cells, are highly functional, pro-inflammatory T cells. These CD161-expressing T cells are critical in immunity against microbes, while possibly contributing to autoimmune diseases. So far, little is known about the impact of aging on the frequency, phenotype, and function of these CD161-expressing T cells. In the current study, we investigated the impact of aging on CD161+ CD4+ T cells, CD161high CD8+ T cells, and CD161int CD8+ T cells in peripheral blood samples of 96 healthy subjects (age 20–84). Frequencies of CD161+ CD4+ T cells and CD161int CD8+ T cells were stable with aging, whereas frequencies of CD161high CD8+ T cells declined. Although CD161high CD8+ T cells were mostly T cell receptor-Vα7. 2+ mucosal-associated invariant T cells, CD161 expressing CD4+ and CD8+ T cells showed a limited expression of markers for gamma–delta T cells or invariant natural killer (NK) T cells, in both young and old subjects. In essence, CD161-expressing T cells showed a similar memory phenotype in young and old subjects. The expression of the inhibitory NK receptor KLRG1 was decreased on CD161+ CD4+ T cells of old subjects, whereas the expression of other NK receptors by CD161-expressing T cells was unaltered with age. The expression of cytotoxic effector molecules was similar in CD161high and CD161int CD8+ T cells of young and old subjects. The ability to produce pro-inflammatory cytokines was preserved in CD161high and CD161int CD8+ T cells of old subjects. However, the percentages of IFN-γ+ and interleukin-17+ cells were significantly lower in CD161+ CD4+ T cells of old individuals than those of young individuals. In addition, aging was associated with a decrease of nonclassic T helper 1 cells, as indicated by decreased percentages of CD161-expressing cells within the IFN-γ+ CD4+ T cell compartment of old subjects. Taken together, aging is associated with a numerical decline of circulating CD161high CD8+ T cells, as well as a decreased production of pro-inflammatory cytokines by CD161+ CD4+ T cells. These aging-associated changes could contribute to perturbed immunity in the elderly.
TEAD4 exerts pro‐metastatic effects and is negatively regulated by miR6839‐3p in lung adenocarcinoma progression

Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour‐promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial‐mesenchymal transition (EMT) markers such as E‐cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4‐targeted microRNA, namely miR6839‐3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839‐3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839‐3p mimics as a promising therapeutic direction.
Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir

Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent.
Clinical efficacy of probiotics as an adjunctive therapy to non-surgical periodontal treatment of chronic periodontitis: a systematic review and meta-analysis.

FOCUSED QUESTION What is the clinical influence of probiotics as an adjunctive therapy of scaling and root planing (SRP) when compared with SRP alone or in combination with placebo in the treatment of chronic periodontitis (CP). METHODS Electronic databases were searched up to July 2015. Randomized controlled trials (RCTs) comparing SRP + probiotic versusSRP were included. PPD reduction and CAL gain were selected as primary outcome variables. RESULTS Independent screening resulted in four eligible publications for the systematic review and three were included in the meta-analysis. Meta-analysis showed a statistically significant CAL gain (-0.42 mm, p = 0.002) and bleeding on probing (BOP) reduction (-14.66, p = 0.003) for SRP + probiotic treatment versusSRP at short-term. Only a tendency (p = 0.06) has been observed in terms of overall PPD reduction, whereas results were significant when stratified for moderate (-0.18, p = 0.001) and deep pockets (-0.67, p < 0.001). CONCLUSION Within the limitations of this study, the findings of this meta-analysis seem to support the adjunctive use of L. reuteri to SRP in CP treatment at short-term, especially in deep pockets. Heterogeneity and limited available data may reduce the impact of these conclusions. Future long-term RCTs evaluating the clinical efficacy of adjunctive probiotics to SRP are needed.
Learning to Navigate in Cities Without a Map

Navigating through unstructured environments is a basic capability of intelligent creatures, and thus is of fundamental interest in the study and development of artificial intelligence. Long-range navigation is a complex cognitive task that relies on developing an internal representation of space, grounded by recognisable landmarks and robust visual processing, that can simultaneously support continuous self-localisation ("I am here") and a representation of the goal ("I am going there"). Building upon recent research that applies deep reinforcement learning to maze navigation problems, we present an end-to-end deep reinforcement learning approach that can be applied on a city scale. Recognising that successful navigation relies on integration of general policies with locale-specific knowledge, we propose a dual pathway architecture that allows locale-specific features to be encapsulated, while still enabling transfer to multiple cities. We present an interactive navigation environment that uses Google StreetView for its photographic content and worldwide coverage, and demonstrate that our learning method allows agents to learn to navigate multiple cities and to traverse to target destinations that may be kilometres away. The project webpage this http URL contains a video summarising our research and showing the trained agent in diverse city environments and on the transfer task, the form to request the StreetLearn dataset and links to further resources. The StreetLearn environment code is available at this https URL
Methods for Estimating Adjusted Risk Ratios

The risk ratio can be a useful statistic for summarizing the results of cross-sectional, cohort, and randomized trial studies. I discuss several methods for estimating adjusted risk ratios and show how they can be executed in Stata, including 1) Mantel–Haenszel and inverse-variance stratified methods; 2) generalized linear regression with a log link and binomial distribution; 3) generalized linear regression with a log link, normal distribution, and robust variance estimator; 4) Poisson regression with a robust variance estimator; 5) Cox proportional hazards regression with a robust variance estimator; 6) standardized risk ratios from logistic, probit, complementary log-log, and log-log regression; and 7) a substitution method. Advantages and drawbacks are noted for some methods.
Spectroscopic insight into the interaction of bovine serum albumin with imidazolium-based ionic liquids in aqueous solution.

The study of protein-ionic liquid interactions is very important because of the widespread use of ionic liquids as protein stabilizer in the recent years. In this work, the interaction of bovine serum albumin (BSA) with different imidazolium-based ionic liquids (ILs) such as [1-ethyl-3-methyl-imidazolium ethyl sulfate (EmimESO4 ), 1-ethyl-3-methyl-imidazolium chloride (EmimCl) and 1-butyl-3-methyl-imidazolium chloride (BmimCl)] has been investigated using different spectroscopic techniques. The intrinsic fluorescence of BSA is quenched by ILs by the dynamic mechanism. The thermodynamic analysis demonstrates that very weak interactions exist between BSA and ILs. 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence and lifetime measurements reveal the formation of the compact structure of BSA in IL medium. The conformational changes of BSA were monitored by CD analysis. Temperature-dependent ultraviolet (UV) measurements were done to study the thermal stability of BSA. The thermal stability of BSA in the presence of ILs follows the trend EmimESO4 > EmimCl > BmimCl and in the presence of more hydrophobic IL, destabilization increases rapidly as a function of concentration.
Sketched covariance testing: A compression-statistics tradeoff

Hypothesis testing of covariance matrices is an important problem in multivariate analysis. Given n data samples and a covariance matrix ∑0, the goal is to determine whether or not the data is consistent with this matrix. In this paper we introduce a framework that we call sketched covariance testing, where the data is provided after being compressed by multiplying by a "sketching" matrix A chosen by the analyst. We propose a statistical test in this setting and quantify an achievable sample complexity as a function of the amount of compression. Our result reveals an intriguing achievable tradeoff between the compression ratio and the statistical information required for reliable hypothesis testing; the sample complexity increases as the fourth power of the amount of compression.
Role of polyphenols and nonpolyphenols against toxicity induced by fluoride: a comprehensive review

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.
Applying a new computer-aided detection scheme generated imaging marker to predict short-term breast cancer risk

This study aims to investigate the feasibility of identifying a new quantitative imaging marker based on false-positives generated by a computer-aided detection (CAD) scheme to help predict short-term breast cancer risk. An image dataset including four view mammograms acquired from 1044 women was retrospectively assembled. All mammograms were originally interpreted as negative by radiologists. In the next subsequent mammography screening, 402 women were diagnosed with breast cancer and 642 remained negative. An existing CAD scheme was applied ‘as is’ to process each image. From CAD-generated results, four detection features including the total number of (1) initial detection seeds and (2) the final detected false-positive regions, (3) average and (4) sum of detection scores, were computed from each image. Then, by combining the features computed from two bilateral images of left and right breasts from either craniocaudal or mediolateral oblique view, two logistic regression models were trained and tested using a leave-one-case-out cross-validation method to predict the likelihood of each testing case being positive in the next subsequent screening. The new prediction model yielded the maximum prediction accuracy with an area under a ROC curve of AUC = 0.65 ± 0.017 and the maximum adjusted odds ratio of 4.49 with a 95% confidence interval of (2.95, 6.83). The results also showed an increasing trend in the adjusted odds ratio and risk prediction scores (p < 0.01). Thus, this study demonstrated that CAD-generated false-positives might include valuable information, which needs to be further explored for identifying and/or developing more effective imaging markers for predicting short-term breast cancer risk.
Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability

Purpose The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). Materials and Methods We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. Results All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. Conclusion Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID.
The mixing evolution and geometric properties of a passive scalar field in turbulent Rayleigh–Bénard convection

We report on measurements of a two-dimensional (2D) dye concentration field in turbulent Rayleigh–Bénard (RB) convection using the planar laser-induced fluorescence technique. The measurements were made in a vertical plane near the sidewall of a rectangular convection cell filled with water and with the Rayleigh number Ra varying from 109 to 1010, all at a fixed Prandtl number Pr=5.3 and Schmidt number Sc=2100. The mixing evolution and geometric properties of the measured passive scalar field are studied. It is shown that the mixing evolution of the passive scalar field in buoyancy-driven turbulence possesses certain features that are similar to those found in other types of turbulent flows, such as turbulent jets and grid-generated turbulence. These features include a power-law decrease in the mean concentration and exponential tails of single-point probability density function along the evolution path. Our results also show that the log-Poisson distribution is universal for the geometric measures of the passive scalar iso-contours, such as the perimeter, area, shape complexity and absolute value of local curvature; and the log-Poisson statistics may be used to model them. Regarding the influence of buoyancy on the turbulent scalar mixing, it is found that the buoyant scale, i.e. the Bolgiano scale ℓB, cannot be identified from the measured geometric properties.
Integrating Renewable Energy Resources into the Smart Grid: Recent Developments in Information and Communication Technologies

Rising energy costs, losses in the present-day electricity grid, risks from nuclear power generation, and global environmental changes are motivating a transformation of the conventional ways of generating electricity. Globally, there is a desire to rely more on renewable energy resources (RERs) for electricity generation. RERs reduce green house gas emissions and may have economic benefits, e.g., through applying demand side management with dynamic pricing so as to shift loads from fossil fuel-based generators to RERs. The electricity grid is presently evolving towards an intelligent grid, the so-called smart grid (SG). One of the major goals of the future SG is to move towards 100% electricity generation from RERs, i.e., towards a 100% renewable grid. However, the disparate, intermittent, and typically widely geographically distributed nature of RERs complicates the integration of RERs into the SG. Moreover, individual RERs have generally lower capacity than conventional fossil-fuel plants, and these RERs are based on a wide spectrum of different technologies. In this article, we give an overview of recent efforts that aim to integrate RERs into the SG. We outline the integration of RERs into the SG along with their supporting communication networks. We also discuss ongoing projects that seek to integrate RERs into the SG around the globe. Finally, we outline future research directions on integrating RERs into the SG.