Miracle-dz/UniFAR-FTUs huggingface dataset:
Pan-cancer analysis of somatic mutations and epigenetic alterations in insulated neighbourhood boundaries

Recent evidence shows that the disruption of constitutive insulated neighbourhoods might lead to oncogene dysregulation. We present here a systematic pan-cancer characterisation of the associations between constitutive boundaries and genome alterations in cancer. Specifically, we investigate the enrichment of somatic mutation, abnormal methylation, and copy number alteration events in the proximity of CTCF bindings overlapping with topological boundaries (junctions) in 26 cancer types. Focusing on CTCF motifs that are both in-boundary (overlapping with junctions) and active (overlapping with peaks of CTCF expression), we find a significant enrichment of somatic mutations in several cancer types. Furthermore, mutated junctions are significantly conserved across cancer types, and we also observe a positive selection of transversions rather than transitions in many cancer types. We also analyzed the mutational signature found on the different classes of CTCF motifs, finding some signatures (such as SBS26) to have a higher weight within in-boundary than off-bounday motifs. Regarding methylation, we find a significant number of over-methylated active in-boundary CTCF motifs in several cancer types; similarly to somatic-mutated junctions, they also have a significant conservation across cancer types. Finally, in several cancer types we observe that copy number alterations tend to overlap with active junctions more often than in matched normal samples. While several articles have recently reported a mutational enrichment at CTCF binding sites for specific cancer types, our analysis is pan-cancer and investigates abnormal methylation and copy number alterations in addition to somatic mutations. Our method is fully replicable and suggests several follow-up tumour-specific analyses.
Knockdown of lncRNA BLACAT1 enhances radiosensitivity of head and neck squamous cell carcinoma cells by regulating PSEN1.

OBJECTIVES This work focused on the function role and underlying mechanism of BLACAT1 in regulating the radiosensitivity of HNSCC cells via PSEN1. METHODS BLACAT1 and PSEN1 expression in HNSCC tissues and cells were measured by qRT-PCR. Kaplan-Meier method and Spearman's correlation analysis determined the prognostic roles and association of BLCAT1 and PSEN1 in HNSCC. The impacts of BLACAT1 and PSEN1, alone and in combination, on radiosensitivity of HNSCC cells were separately assessed through CCK-8, colony formation, flow cytometry, western blot and γH2AX foci staining assays. RESULTS Our study disclosed that BLACAT1 and PSEN1 were both in association with poor prognosis and radioresistance of HNSCC cells. BLACAT1 knockdown improved the radiosensitivity of HNSCC cells by changing cellular activities containing repressed cell viability, accelerated cell apoptosis, induced cell cycle arrest, and stimulated DNA damage response. Further, we found that PSEN1 was positively correlated with BLACAT1. Rescue assays confirmed that BLACAT1 regulated the radiosensitivity of HNSCC cells by modulating PSEN1. CONCLUSIONS We revealed that BLACAT1 knockdown enhanced radioresistance of HNSCC cells via regulating PSEN1, exposing the probable target role of BLACAT1 in HNSCC. ADVANCES IN KNOWLEDGE This was the first time that the pivotal role of BLACAT1 was investigated in HNSCC, which provided a novel therapeutic direction for HNSCC patients.
VRIA: A Web-Based Framework for Creating Immersive Analytics Experiences

We present VRIA, a Web-based framework for creating Immersive Analytics (IA) experiences in Virtual Reality. VRIA is built upon WebVR, A-Frame, React and D3.js, and offers a visualization creation workflow which enables users, of different levels of expertise, to rapidly develop Immersive Analytics experiences for the Web. The use of these open-standards Web-based technologies allows us to implement VR experiences in a browser and offers strong synergies with popular visualization libraries, through the HTML Document Object Model (DOM). This makes VRIA ubiquitous and platform-independent. Moreover, by using WebVR's progressive enhancement, the experiences VRIA creates are accessible on a plethora of devices. We elaborate on our motivation for focusing on open-standards Web technologies, present the VRIA creation workflow and detail the underlying mechanics of our framework. We also report on techniques and optimizations necessary for implementing Immersive Analytics experiences on the Web, discuss scalability implications of our framework, and present a series of use case applications to demonstrate the various features of VRIA. Finally, we discuss current limitations of our framework, the lessons learned from its development, and outline further extensions.
Small Molecule Antagonists of the RIG-I Innate Immune Receptor.

The RIG-I receptor plays a key role in the vertebrate innate immune system, where it functions as a sensor for detecting infection by RNA viruses. Although agonists of RIG-I show great potential as antitumor and antimicrobial therapies, antagonists of RIG-I remain undeveloped, despite the role of RIG-I hyperstimulation in a range of diseases, including COPD and autoimmune disorders. There is now a wealth of information on RIG-I structure, enzymatic function and signaling mechanism that can drive new drug design strategies. Here, we used the enzymatic activity of RIG-I to develop assays for high-throughput screening, SAR and downstream optimization of RIG-I antagonists. Using this approach, we have developed potent RIG-I antagonists that interact directly with the receptor, and which inhibit RIG-I signaling and interferon response in living cells.
Components from the Human c-myb Transcriptional Regulation System Reactivate Epigenetically Repressed Transgenes

A persistent challenge for mammalian cell engineering is the undesirable epigenetic silencing of transgenes. Foreign DNA can be incorporated into closed chromatin before and after it has been integrated into a host cell’s genome. To identify elements that mitigate epigenetic silencing, we tested components from the c-myb and NF-kB transcriptional regulation systems in transiently transfected DNA and at chromosomally integrated transgenes in PC-3 and HEK 293 cells. DNA binding sites for MYB (c-myb) placed upstream of a minimal promoter enhanced expression from transiently transfected plasmid DNA. We targeted p65 and MYB fusion proteins to a chromosomal transgene, UAS-Tk-luciferase, that was silenced by ectopic Polycomb chromatin complexes. Transient expression of Gal4-MYB induced an activated state that resisted complete re-silencing. We used custom guide RNAs and dCas9-MYB to target MYB to different positions relative to the promoter and observed that transgene activation within ectopic Polycomb chromatin required proximity of dCas9-MYB to the transcriptional start site. Our report demonstrates the use of MYB in the context of the CRISPR-activation system, showing that DNA elements and fusion proteins derived from c-myb can mitigate epigenetic silencing to improve transgene expression in engineered cell lines.
Bimodal Automated Carotid Ultrasound Segmentation Using Geometrically Constrained Deep Neural Networks

For asymptomatic patients suffering from carotid stenosis, the assessment of plaque morphology is an important clinical task which allows monitoring of the risk of plaque rupture and future incidents of stroke. Ultrasound Imaging provides a safe and non-invasive modality for this, and the segmentation of media-adventitia boundaries and lumen-intima boundaries of the Carotid artery form an essential part in this monitoring process. In this paper, we propose a novel Deep Neural Network as a fully automated segmentation tool, and its application in delineating both the media-adventitia boundary and the lumen-intima boundary. We develop a new geometrically constrained objective function as part of the Network's Stochastic Gradient Descent optimisation, thus tuning it to the problem at hand. Furthermore, we also apply a bimodal fusion of amplitude and phase congruency data proposed by us in previous work, as an input to the network, as the latter provides an intensity-invariant data source to the network. We finally report the segmentation performance of the network on transverse sections of the carotid. Tests are carried out on an augmented dataset of 81,000 images, and the results are compared to other studies by reporting the DICE coefficient of similarity, modified Hausdorff Distance, sensitivity and specificity. Our proposed modification is shown to yield improved results on the standard network over this larger dataset, with the advantage of it being fully automated. We conclude that Deep Neural Networks provide a reliable trained manner in which carotid ultrasound images may be automatically segmented, using amplitude data and intensity invariant phase congruency maps as a data source.
Extracting lung function measurements to enhance phenotyping of chronic obstructive pulmonary disease (COPD) in an electronic health record using automated tools

Background Chronic obstructive pulmonary disease (COPD) is associated with poor quality of life, hospitalization and mortality. COPD phenotype includes using pulmonary function tests to determine airflow obstruction from the forced expiratory volume in one second (FEV1):forced vital capacity. FEV1 is a commonly used value for severity but is difficult to identify in structured electronic health record (EHR) data. Data source and methods Using the Microsoft SQL Server’s full-text search feature and string functions supporting regular-expression-like operations, we developed an automated tool to extract FEV1 values from progress notes to improve ascertainment of FEV1 in EHR in the Veterans Aging Cohort Study (VACS). Results The automated tool increased quantifiable FEV1 values from 12,425 to 16,274 (24% increase in numeric FEV1). Using chart review as the reference, positive predictive value of the tool was 99% (95% Confidence interval: 98.2–100.0%) for identifying quantifiable FEV1 values and a recall value of 100%, yielding an F-measure of 0.99. The tool correctly identified FEV1 measurements in 95% of cases. Conclusion A SQL-based full text search of clinical notes for quantifiable FEV1 is efficient and improves the number of values available in VA data. Future work will examine how these methods can improve phenotyping of patients with COPD in the VA.
Combining Measurements of Built-up Area, Nighttime Light, and Travel Time Distance for Detecting Changes in Urban Boundaries: Introducing the BUNTUS Algorithm

This paper introduces a new algorithm (BUNTUS—Built-up, Nighttime Light, and Travel time for Urban Size) using remote sensing techniques to delineate urban boundaries. The paper is part of a larger study of the role of urbanisation in changing fossil fuel emissions. The method combines estimates of land cover, nighttime lights, and travel times to classify contiguous urban areas. The method is automatic, global and uses data sets with enough duration to establish trends. Validation using ground truth from Landsat-8 OLI images revealed an overall accuracy ranging from 60% to 95%. Thus, this approach is capable of describing spatial distributions and giving detailed information of urban extents. We demonstrate the method with examples from Brisbane, Australia, Melbourne, Australia, and Beijing, China. The new method meets the criteria for studying overall trends in urban emissions.
Cytological aspiration biopsy of goiters, especially with reference to their histological and cytological examinations

The purpose of this paper is to examine whetherthe cytological fine needle aspiration biopsy is useful, or not, to make settled diagnosis of diseasewith goiter. To study this possibility, both histological and cytological examinations were made onthe same case.A new instrument for the aspiration biopsy wasused in this study. The instrument is devised soas to be fitted, without any aseptic precaution, witha 10ml syringe, which is usually used in a clinic. Afine needle, 6 cm in length and 0.7mm in outerdiameter, is attached to the syringe.Using the instrument, the aspiration biopsy wasapplied to 123 patients with goiters, the histologicalclassification of which consisted of 25 carcinomas, 42 adenomas, 10 simple cysts, 25 Graves' diseases, 15 Hashimoto's diseases, 5 adenomatous goiters andone subacute thyroiditis.The conclusions of this study are as follow:1. In 121 of 123 examined cases, aspirated cellswere sufficient for diagnosis. Both the remainingcases histologically showed “adenocarcinoma withmassive fibrosis and scant tumor cells”. 2. No complication of hemorrhage, infection ortumor cell spreading was accompanied by this procedure.3. The smear from thyroid carcinoma was usually abundant in cancer cells. Frequently, they ga- thered to form characteristic clusters of cells, which were large in size and showed irregular anddense crowding of cells. Although the cancer cellsaspirated from the thyroid also showed the generalfeatures of malignant cells, it was peculiar to theformers that many of their nuclei had rather finegranuloreticular patterns of chromatin structure.4. Adenoma cells considerably differed in morphology from cancer cells, and cytological diagnosisof benign adenoma was not so difficult.5. The diagnosis of cyst was determined byaspiration of massive fluid and observation of characteristic foamy cells.6. There were medium-sized to small clustersin the aspiration smears of Graves' diseases, all ofwhich had fallen into euthyroidism with treatments.The epithelial cells, of which the clusters consisted, were slight in atipism, large in size and regular in arrangement.7. Cytological diagnosis of Hashimoto's diseasewas based upon a large number of lymphocytes anda few degenerative epithelial cells.8. Some characteristic, multinucleated giantcells were aspirated from a goiter of subacute thyroiditis.9. Based upon such cytological features of aspiration smears from various kinds of goiters asmentioned above, cyto-diagnosis was retrospectivelytried again on the blind specimens of 123 examinedcases. In 21 out of 25 thyroid cancers, cyto-diagnosis of cancer was settled, in one case cancerwas suspected, in one a diagnosis of benign adenoma was made, and in 2 the cells were too insufficiently aspirated to an exact cyto-diagnosis. In addition, there was one false-positive
Geometric morphometric analysis of malocclusion on lateral cephalograms in Malaysian population

Geometric morphometrics is a new approach for shape identification in diagnosis of malocclusion. Lateral cephalogram is an X-ray that taken for diagnosing malocclusion in dental setting. The aim of this study was to determine the differences of craniofacial shape in malocclusion by application of two-dimensional geometric morphometrics and to compile the database of malocclusion in adult Malaysian population. Lateral cephalogram radiographs of 381 adults Malaysia (age 18–45) were retrieved retrospectively and assigned to three groups according to their occlusion: class I, class II, and class III. The geometric morphometric shape study incorporated nine landmarks and was analyzed in details using tpsUtil p software. Geometric morphometric analysis such was done using MorphoJ software. The results of the principal component's analysis (PCA) yielded 14 main components responsible for 100% of the variation exhibited by the malocclusion with three highly significant PCA. The highest Mahalanobis distances were exhibited by the malocclusion class II and III population. The Procrustes ANOVA showed that the shape effect was highly significant (P<0.01). The discriminant function analysis showed the high percentage of 80% discriminate among the malocclusions after cross-validation. There are significant differences for ANB angle (A point-Nasion-B point) in all malocclusion groups. Class II has the widest ANB angle while class III has the most acute ANB angle. Skeletal shape was clearly associated with dental malocclusion and showed considerable variation. Geometric morphometrics is an alternative research tool and can be used for diagnosing individual classification of malocclusion.
How many bots are you following?

Social Media are evolving as a pervasive source of news able to reach a larger audience through their spreading power. The main drawback is given by the presence of malicious accounts, known as social bots, which are often used to diffuse misleading information. Social bots are automated accounts whose goal is to interact with humans and influence them. Starting from the definition of credulous (i.e., human accounts with a high percentage of bot friends among their followees, in this work we aim to single out a regression model to derive, with an acceptable margin of error, the percentage of bot-followees of a human-operated account. The advantage lies in knowing, as a preventive measure, which users may be the target of bots' activities, hence more exposed to the misleading/unreliable content. Our results showed that the best regression model achieves a Mean Absolute Error of 3.62% and a Root Mean Squared Error of 5.96%, thus encouraging further research in this direction.
Parents’ underestimation of their child’s weight status. Moderating factors and change over time: A cross-sectional study

Background Parents’ underestimation of their child’s weight status can hinder active participation in overweight prevention programs. We examined the level of agreement between the parents’ perception of their child’s weight status and the child’s actual weight status, moderating factors, and change over time. Methods This cross-sectional study used data collected in 2009 (n = 8105), 2013 (n = 8844) and 2017 (n = 11,022) from a community-based survey conducted among parents of children age 2–12 years in the Netherlands. Parents classified their perception of their child’s weight status on a 5-point Likert scale. In 2009 and 2013, the child’s BMI was calculated from self-reported data by parents. The level of agreement between the parent’s perception of the weight status and the actual weight status was examined using Cohen’s kappa. The role of demographic factors on parents’ perception were examined using logistic regression. Results In 2009, 2013 and 2017, 6%, 6% and 5% of the parents, respectively, classified their child as heavy/extremely heavy. In 2009 and 2013, 64.7% and 61.0% of parents, respectively, underestimated the weight status of their overweight child. This was even higher among parents of obese children. Overall, the agreement between the parents’ perception and the actual weight status improved from 2009 (kappa = 0.38) to 2013 (kappa = 0.43) (p<0.05), but remained unsatisfactory. The parents’ underestimation of their child’s overweight/obesity status was associated with the child’s age in 2009 and 2013 (2–7 years; OR: 0.18), the child’s gender in 2009 (male; OR: 0.55), and the parents’ education level in 2009 (middle and high education; OR: 0.56 and 0.44 respectively). Conclusions Parents’ underestimation of their child’s weight status remains alarmingly high, particularly among parents of young, obese children. This underestimation is a barrier to preventing childhood overweight/obesity. Healthcare professionals should take this underestimation into consideration and should actively encourage parents to take steps to prevent overweight/obesity in their children.
Anti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats

Background The purpose of the present study was to evaluate the regulatory effects of acetyl-L-carnitine (ALCAR) on atherosclerosis in Wister rats and to explore its anti-atherosclerotic mechanism. Material/Methods We randomly divided 32 Wister rats into 4 groups: a normal diet group (control group, n=8), a normal diet+ALCAR group (ALCAR group, n=8), an atherosclerosis group (AS group, n=8), and an atherosclerosis+ALCAR group (AS+ALCAR group, n=8). The serum lipid distribution, oxidative stress, inflammatory factors and adiponectin (APN) in the blood, and heart and aortic tissues were determined using the standard assay kits, xanthine oxidase method, and ELISA, respectively. HE staining was performed to observe aortic pathology structure change, and the level of angiotensin II (AngII) in the aorta was assessed using radioimmunoassay. In addition, real-time quantitative PCR and Western blot analysis were applied to detect the expression of iNOS, IL-1β, TNF-α, and CRP in the aortic and heart tissues. Results Compared with the AS group, the levels of serum TC, TG, LDL, and VLDL in rats decreased significantly, while HDL level significantly increased in the AS+ALCAR group. ALCAR administration enhanced the SOD and GSH-Px activities and decreased MDA activity. APN level was significantly elevated in the AS group, but ALCAR had no significant effect on APN. Further, ALCAR reduced the expressions of inflammation factors TNF-α, IL-1β, iNOS, and CRP, and the concentration of AngII in serum, aortic, and heart tissues. Conclusions ALCAR can inhibit the expressions of inflammatory factors and antioxidation to suppress the development of atherosclerosis by adjusting blood lipid in the myocardium of AS rats.
DNA Repair and the Stability of the Plant Mitochondrial Genome

The mitochondrion stands at the center of cell energy metabolism. It contains its own genome, the mtDNA, that is a relic of its prokaryotic symbiotic ancestor. In plants, the mitochondrial genetic information influences important agronomic traits including fertility, plant vigor, chloroplast function, and cross-compatibility. Plant mtDNA has remarkable characteristics: It is much larger than the mtDNA of other eukaryotes and evolves very rapidly in structure. This is because of recombination activities that generate alternative mtDNA configurations, an important reservoir of genetic diversity that promotes rapid mtDNA evolution. On the other hand, the high incidence of ectopic recombination leads to mtDNA instability and the expression of gene chimeras, with potential deleterious effects. In contrast to the structural plasticity of the genome, in most plant species the mtDNA coding sequences evolve very slowly, even if the organization of the genome is highly variable. Repair mechanisms are probably responsible for such low mutation rates, in particular repair by homologous recombination. Herein we review some of the characteristics of plant organellar genomes and of the repair pathways found in plant mitochondria. We further discuss how homologous recombination is involved in the evolution of the plant mtDNA.
Monitoring status and evaluating outcomes: An overview of rating scales for use with patients who have sustained a stroke

Evaluating outcomes of rehabilitation is currently an interest of both clinicians and researchers. This article reviews issues involved in choosing measures to assess outcomes and presents selected rating scales for use with patients who have sustained a stroke. The psychometric properties of a measure as well as practical considerations should influence choice. Rating scales to assess impairments and basic activities of daily living are well developed and commonly used. Standardized scales to assess instrumental activities or handicaps are scarce, whereas measures of quality of life are available but seldom employed in stroke studies. Expanding the use of rating scales is important in clinical practice and stroke research.