Miracle-dz/UniFAR-FTUs huggingface dataset:
VEGF-B gene therapy inhibits doxorubicin-induced cardiotoxicity by endothelial protection

Significance The cardiotoxicity of anthracyclines is a major problem in cancer chemotherapy, and its alleviation would improve the life expectancy of cancer patients. This study shows that vascular endothelial growth factor-B (VEGF-B) gene therapy can be used to prevent the cardiotoxicity of doxorubicin (DOX). VEGF-B inhibited DOX-induced cardiac atrophy, protected endothelial cells from apoptosis, and preserved the myocardial capillary network. Importantly, DOX-induced whole body wasting (cachexia), which both impairs the quality of life and increases drug toxicity in patients as well as decreases their survival, was inhibited by VEGF-B treatment in the DOX-treated mice. Additional preclinical studies are needed for development of the VEGF-B gene therapy for cardiac protection in patients. Congestive heart failure is one of the leading causes of disability in long-term survivors of cancer. The anthracycline antibiotic doxorubicin (DOX) is used to treat a variety of cancers, but its utility is limited by its cumulative cardiotoxicity. As advances in cancer treatment have decreased cancer mortality, DOX-induced cardiomyopathy has become an increasing problem. However, the current means to alleviate the cardiotoxicity of DOX are limited. We considered that vascular endothelial growth factor-B (VEGF-B), which promotes coronary arteriogenesis, physiological cardiac hypertrophy, and ischemia resistance, could be an interesting candidate for prevention of DOX-induced cardiotoxicity and congestive heart failure. To study this, we administered an adeno-associated viral vector expressing VEGF-B or control vector to normal and tumor-bearing mice 1 wk before DOX treatment, using doses mimicking the concentrations used in the clinics. VEGF-B treatment completely inhibited the DOX-induced cardiac atrophy and whole-body wasting. VEGF-B also prevented capillary rarefaction in the heart and improved endothelial function in DOX-treated mice. VEGF-B also protected cultured endothelial cells from apoptosis and restored their tube formation. VEGF-B increased left ventricular volume without compromising cardiac function, reduced the expression of genes associated with pathological remodeling, and improved cardiac mitochondrial respiration. Importantly, VEGF-B did not affect serum or tissue concentrations of DOX or augment tumor growth. By inhibiting DOX-induced endothelial damage, VEGF-B could provide a novel therapeutic possibility for the prevention of chemotherapy-associated cardiotoxicity in cancer patients.
Directly Measured Physical Function in Cardiac Rehabilitation

PURPOSE: The Short Physical Performance Battery (SPPB) is a strong predictor for risk of physical disability in older adults. Roughly half of individuals participating in phase II cardiac rehabilitation (CR) are 65 years or older, many presenting with low aerobic capacities and may be at increased risk for physical disability. METHODS: The cohort consisted of 196 consecutive patients (136 men), aged 65 years or older, entering CR who were prospectively evaluated by the SPPB. Data were also obtained for age, self-reported physical function (Medical Outcomes Study Short Form-36 questionnaire), and peak aerobic capacity. Measures were repeated upon completion of CR for those individuals who completed the program. RESULTS: The average age of patients was 74 ± 0.5 years. At baseline, total SPPB score was 9.7 ± 0.2 (out of 12). Followup data were obtained on 133 (68%) patients, with a mean improvement of 0.8 ± 0.1 (P < .0001), which was not clinically significant (≥1 point). Focusing on patients with a low baseline SPPB score, 72 subjects scored ⩽9 (7.1 ± 0.2), with 45 completing exit measures. Improvements were found in gait speed (0.5 ± 0.1, P < .0001), chair-stand (1.0 ± 0.1, P < .0001), and total SPPB (1.6 ± 0.3, P < .0001) in this more disabled group. Measures of O2peak were significantly reduced in the low SPPB group (13.5 ± 0.4 vs 17.5 ± 0.4 mL/kg/min, P < .0001). Measured O2peak (R 2 = 26%, P < .0001) and self-reported physical function score (R 2 = 5%, P = .02) were the only multivariate predictors of baseline SPPB. CONCLUSION: For patients who enter CR with low SPPB scores (37%), significant improvements in physical function were noted, largely explained by improved walking speed and leg strength (chair-stand).
Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

ABSTRACT Introduction: Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration. Areas covered: This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery. Expert opinion: Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.
PROMIS GH (Patient-Reported Outcomes Measurement Information System Global Health) Scale in Stroke: A Validation Study

Background and Purpose— The International Consortium for Health Outcomes Measurement recently included the 10-item PROMIS GH (Patient-Reported Outcomes Measurement Information System Global Health) scale as part of their recommended Standard Set of Stroke Outcome Measures. Before collection of PROMIS GH is broadly implemented, it is necessary to assess its performance in the stroke population. The objective of this study was to evaluate the psychometric properties of PROMIS GH in patients with ischemic stroke and intracerebral hemorrhage. Methods— PROMIS GH and 6 PROMIS domain scales measuring same/similar constructs were electronically collected on 1102 patients with ischemic and hemorrhagic strokes at various stages of recovery from their stroke who were seen in a cerebrovascular clinic from October 12, 2015, through June 2, 2017. Confirmatory factor analysis was performed to evaluate the adequacy of 2-factor structure of component scores. Test–retest reliability and convergent validity of PROMIS GH items and component scores were assessed. Discriminant validity and responsiveness were compared between PROMIS GH and PROMIS domain scales measuring the same or related constructs. Analyses were repeated stratified by stroke subtype and modified Rankin Scale score <2 versus ≥2. Results— There was moderate internal reliability (ordinal &agr;, 0.82–0.88) and marginal model fit for the 2-factor solution for component scores (root mean square error of approximation, 0.11). Convergent validity was good with significant correlations between all PROMIS GH items and PROMIS domain scales (P<0.001 for all). There was excellent discrimination for all PROMIS GH items and component scores across modified Rankin Scale levels. Good responsiveness (effect size, >0.5) was demonstrated for 8 of the 10 PROMIS GH items. Reliability and validity remained consistent across stroke subtype and disability level (modified Rankin Scale, <2 versus ≥2). Conclusions— PROMIS GH exhibits acceptable performance in patients with stroke. Our findings support International Consortium for Health Outcomes Measurement recommendation to use PROMIS GH as part of the standard set of outcome measures in stroke.
Inferring anchor links across multiple heterogeneous social networks

Online social networks can often be represented as heterogeneous information networks containing abundant information about: who, where, when and what. Nowadays, people are usually involved in multiple social networks simultaneously. The multiple accounts of the same user in different networks are mostly isolated from each other without any connection between them. Discovering the correspondence of these accounts across multiple social networks is a crucial prerequisite for many interesting inter-network applications, such as link recommendation and community analysis using information from multiple networks. In this paper, we study the problem of anchor link prediction across multiple heterogeneous social networks, i.e., discovering the correspondence among different accounts of the same user. Unlike most prior work on link prediction and network alignment, we assume that the anchor links are one-to-one relationships (i.e., no two edges share a common endpoint) between the accounts in two social networks, and a small number of anchor links are known beforehand. We propose to extract heterogeneous features from multiple heterogeneous networks for anchor link prediction, including user's social, spatial, temporal and text information. Then we formulate the inference problem for anchor links as a stable matching problem between the two sets of user accounts in two different networks. An effective solution, MNA (Multi-Network Anchoring), is derived to infer anchor links w.r. t. the one-to-one constraint. Extensive experiments on two real-world heterogeneous social networks show that our MNA model consistently outperform other commonly-used baselines on anchor link prediction.
Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax

ABSTRACT To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. IMPORTANCE EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. This study provides evidence that EV71 induces cell apoptosis by modulating Bax activation and reveals important clues regarding the mechanism of Cyt c release and mitochondrial permeabilization during EV71 infection.
Chest computed tomography-derived low fat-free mass index and mortality in COPD

Low fat-free mass index (FFMI) is an independent risk factor for mortality in chronic obstructive pulmonary disease (COPD) not typically measured during routine care. In the present study, we aimed to derive fat-free mass from the pectoralis muscle area (FFMPMA) and assess whether low FFMIPMA is associated with all-cause mortality in COPD cases. We used data from two independent COPD cohorts, ECLIPSE and COPDGene. Two equal sized groups of COPD cases (n=759) from the ECLIPSE study were used to derive and validate an equation to calculate the FFMPMA measured using bioelectrical impedance from PMA. We then applied the equation in COPD cases (n=3121) from the COPDGene cohort, and assessed survival. Low FFMIPMA was defined, using the Schols classification (FFMI <16 in men, FFMI <15 in women) and the fifth percentile normative values of FFMI from the UK Biobank. The final regression model included PMA, weight, sex and height, and had an adjusted R2 of 0.92 with fat-free mass (FFM) as the outcome. In the test group, the correlation between FFMPMA and FFM remained high (Pearson correlation=0.97). In COPDGene, COPD cases with a low FFMIPMA had an increased risk of death (HR 1.6, p<0.001). We demonstrated COPD cases with a low FFMIPMA have an increased risk of death. Low fat-free mass index (FFMI) derived from chest CT is associated with reduced survival among COPD cases http://ow.ly/KNaU30gsFZM
Motivated Reasoning During Recruitment

This research shows how job postings can lead job candidates to see themselves as particularly deserving of hiring and high salary. We propose that these entitlement beliefs entail both personal motivations to see oneself as deserving and the ability to justify those motivated judgments. Accordingly, we predict that people feel more deserving when qualifications for a job are vague and thus amenable to motivated reasoning, whereby people use information selectively to reach a desired conclusion. We tested this hypothesis with a 2-phase experiment (N = 892) using materials drawn from real online job postings. In the first phase of the experiment, participants believed themselves to be more deserving of hiring and deserving of higher pay after reading postings composed of vaguer types of qualifications. In the second phase, yoked observers believed that participants were less entitled overall, but did not selectively discount endorsement of vaguer qualifications, suggesting they were unaware of this effect. A follow-up preregistered experiment (N = 905) using postings with mixed qualification types replicated the effect of including more vague qualifications on participants’ entitlement beliefs. Entitlement beliefs are widely seen as problematic for recruitment and retention, and these results suggest that reducing the inclusion of vague qualifications in job postings would dampen the emergence of these beliefs in applicants, albeit at the cost of decreasing application rates and lowering applicants’ confidence.
Antioxidant properties and global metabolite screening of the probiotic yeast Saccharomyces cerevisiae var. boulardii.

BACKGROUND Saccharomyces cerevisiae var. boulardii is the only yeast species with probiotic properties. It is considered to have therapeutic significance in gastrointestinal disorders. In the present study, a comparative physiological study between this yeast and Saccharomyces cerevisiae (BY4742) was performed by evaluating two prominent traits of probiotic species, responses to different stress conditions and antioxidant capacity. A global metabolite profile was also developed aiming to identify which therapeutically important secondary metabolites are produced. RESULTS Saccharomyces cerevisiae var. boulardii showed no significant difference in growth patterns but greater stress tolerance compared to S. cerevisiae. It also demonstrated a six- to 10-fold greater antioxidant potential (judged by the 1,1-diphenyl-2-picrylhydrazyl assay), with a 70-fold higher total phenolic content and a 20-fold higher total flavonoid content in the extracellular fraction. These features were clearly differentiated by principal component analysis and further indicated by metabolite profiling. The extracellular fraction of the S. cerevisiae var. boulardii cultures was found to be rich in polyphenolic metabolites: vanillic acid, cinnamic acid, phenyl ethyl alcohol (rose oil), erythromycin, amphetamine and vitamin B6 , which results in the antioxidant capacity of this strain. CONCLUSION The present study presents a new perspective for differentiating the two genetically related strains of yeast, S. cerevisiae and S. cerevisiae var. boulardii by assessing their metabolome fingerprints. In addition to the correlation of the phenotypic properties with the secretory metabolites of these two yeasts, the present study also emphasizes the potential to exploit S. cerevisiae var. boulardii in the industrial production of these metabolites. © 2016 Society of Chemical Industry.
A Computational Approach From Gene to Structure Analysis of the Human ABCA4 Transporter Involved in Genetic Retinal Diseases.

Purpose The aim of this article is to report the investigation of the structural features of ABCA4, a protein associated with a genetic retinal disease. A new database collecting knowledge of ABCA4 structure may facilitate predictions about the possible functional consequences of gene mutations observed in clinical practice. Methods In order to correlate structural and functional effects of the observed mutations, the structure of mouse P-glycoprotein was used as a template for homology modeling. The obtained structural information and genetic data are the basis of our relational database (ABCA4Database). Results Sequence variability among all ABCA4-deposited entries was calculated and reported as Shannon entropy score at the residue level. The three-dimensional model of ABCA4 structure was used to locate the spatial distribution of the observed variable regions. Our predictions from structural in silico tools were able to accurately link the functional effects of mutations to phenotype. The development of the ABCA4Database gathers all the available genetic and structural information, yielding a global view of the molecular basis of some retinal diseases. Conclusions ABCA4 modeled structure provides a molecular basis on which to analyze protein sequence mutations related to genetic retinal disease in order to predict the risk of retinal disease across all possible ABCA4 mutations. Additionally, our ABCA4 predicted structure is a good starting point for the creation of a new data analysis model, appropriate for precision medicine, in order to develop a deeper knowledge network of the disease and to improve the management of patients.
Optical flow based velocity estimation for mobile robots

This paper presents an optical flow based novel technique to perceive the instant motion velocity of mobile robots. The primary focus of this study is to determine the robot’s ego-motion using displacement field in temporally consecutive image pairs. In contrast to most previous approaches for estimating velocity, we employ a polynomial expansion based dense optical flow approach and propose a quadratic model based RANSAC refinement of flow fields to render our method more robust with respect to noise and outliers. Accordingly, techniques for geometrical transformation and interpretation of the inter-frame motion are presented. Advantages of our proposal are validated by real experimental results conducted on Pioneer robot.
Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis

In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post‐mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact‐appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron‐autonomous and neuroglia‐mediated mechanisms of synaptic degradation in chronic multiple sclerosis.
A Simple and Effective Measure for Complex Low-Level Dependencies

The measure dep-degree is a simple indicator for structural problems and complex dependencies on code-level. We model low-level dependencies between program operations as use-def graph, which is generated from reaching definitions of variables. The more dependencies a program operation has, the more different program states have to be considered and the more difficult it is to understand the operation. Dep-degree is simple to compute and interpret, flexible and scalable in its application, and independently complementing other indicators. Preliminary experiments suggest that the measure dep-degree, which simply counts the number of dependency edges in the use-def graph, is a good indicator for readability and understandablity.