Miracle-dz/UniFAR-FTUs huggingface dataset:
Microvesicles in vascular homeostasis and diseases

Summary Microvesicles are members of the family of extracellular vesicles shed from the plasma membrane of activated or apoptotic cells. Microvesicles were initially characterised by their pro-coagulant activity and described as “microparticles”. There is mounting evidence revealing a role for microvesicles in intercellular communication, with particular relevance to hemostasis and vascular biology. Coupled with this, the potential of microvesicles as meaningful biomarkers is under intense investigation. This Position Paper will summarise the current knowledge on the mechanisms of formation and composition of microvesicles of endothelial, platelet, red blood cell and leukocyte origin. This paper will also review and discuss the different methods used for their analysis and quantification, will underline the potential biological roles of these vesicles with respect to vascular homeostasis and thrombosis and define important themes for future research.
Automatic assessment of bone age using statistical models of appearance and Random Forest Regression voting

This work addresses the problem of automatic estimation of bone age in children and young adults. Bone age assessment is important for diagnosing and monitoring growth and endocrine disorders. We have constructed a system which uses Statistical Models of Shape and Appearance to locate bones in a radiograph and to predict bone age. By analyzing the performance on a data-set of about 600 digitized radiograph of normal children we show how Random Forest Regression voting in a Contrained Local models framework (RFRV — CLM) are sufficient to initialize an automatic registration algorithm. We built global models of whole hand and local models of individual bones. We used the same RFRV — CLM models to locate salient bones of the hand. We improved our age estimation results by using multiple local age group models and multiple local age predictors. We obtained an accuracy of mean point-to-point errors of 0.87mm on sparse points placement for initialization of automatic registrations. Our Bone age assessment methodology achieved an accuracy of mean absolute error of 0.41±0.02 years and 0.47 ± 0.03 years for female and male respectively.
Who perpetrates violence against children? A systematic analysis of age-specific and sex-specific data

Objective The epidemiology of violence against children is likely to differ substantially by sex and age of the victim and the perpetrator. Thus far, investment in effective prevention strategies has been hindered by lack of clarity in the burden of childhood violence across these dimensions. We produced the first age-specific and sex-specific prevalence estimates by perpetrator type for physical, sexual and emotional violence against children globally. Design We used random effects meta-regression to estimate prevalence. Estimates were adjusted for relevant quality covariates, variation in definitions of violence and weighted by region-specific, age-specific and sex-specific population data to ensure estimates reflect country population structures. Data sources Secondary data from 600 population or school-based representative datasets and 43 publications obtained via systematic literature review, representing 13 830 estimates from 171 countries. Eligibility criteria for selecting studies Estimates for recent violence against children aged 0–19 were included. Results The most common perpetrators of physical and emotional violence for both boys and girls across a range of ages are household members, with prevalence often surpassing 50%, followed by student peers. Children reported experiencing more emotional than physical violence from both household members and students. The most common perpetrators of sexual violence against girls aged 15–19 years are intimate partners; however, few data on other perpetrators of sexual violence against children are systematically collected internationally. Few age-specific and sex-specific data are available on violence perpetration by schoolteachers; however, existing data indicate high prevalence of physical violence from teachers towards students. Data from other authority figures, strangers, siblings and other adults are limited, as are data on neglect of children. Conclusions Without further investment in data generation on violence exposure from multiple perpetrators for boys and girls of all ages, progress towards Sustainable Development Goals 4, 5 and 16 may be slow. Despite data gaps, evidence shows violence from household members, peers in school and for girls, from intimate partners, should be prioritised for prevention. Trial registration number PROSPERO 2015: CRD42015024315.
Synergistic antitumor effects of tanshinone IIA and sorafenib or its derivative SC-1 in hepatocellular carcinoma cells

Introduction Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancy in the world. We aimed to determine the effect of tanshinone IIA (Tan-IIA) in combination with sorafenib or its derivative SC-1 on cytotoxicity, apoptosis, and metastasis in human HCC cells. Materials and methods Cytotoxicity was detected by MTT assay. Apoptosis and sub-G1 populations were analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. Protein expression was detected by Western blot. Results Tan-IIA combined with sorafenib or SC-1 exerted synergistic cytotoxicity in HCC cells. Elevated proportions of sub-G1 and caspase activation were observed in the combinative treatments; in addition, marked inhibition of cell migration and invasion, which could be mediated by the modulation of epithelial–mesenchymal transition was observed. pSTAT3 levels were significantly reduced as well. Conclusion A combination therapy using Tan-IIA and sorafenib or SC-1 could be a promising approach to target HCC, and further preclinical investigations are warranted to establish their synergetic advantage.
Full Spectrum Sharing in Cognitive Radio Networks Toward 5G: A Survey

With the development of wireless communication technology, the need for bandwidth is increasing continuously, and the growing need makes wireless spectrum resources more and more scarce. Cognitive radio (CR) has been identified as a promising solution for the spectrum scarcity, and its core idea is the dynamic spectrum access. It can dynamically utilize the idle spectrum without affecting the rights of primary users, so that multiple services or users can share a part of the spectrum, thus achieving the goal of avoiding the high cost of spectrum resetting and improving the utilization of spectrum resources. In order to meet the critical requirements of the fifth generation (5G) mobile network, especially the Wider-Coverage, Massive-Capacity, Massive-Connectivity, and Low-Latency four application scenarios, the spectrum range used in 5G will be further expanded into the full spectrum era, possibly from 1 GHz to 100 GHz. In this paper, we conduct a comprehensive survey of CR technology and focus on the current significant research progress in the full spectrum sharing towards the four scenarios. In addition, the key enabling technologies that may be closely related to the study of 5G in the near future are presented in terms of full-duplex spectrum sensing, spectrum-database based spectrum sensing, auction based spectrum allocation, carrier aggregation based spectrum access. Subsequently, other issues that play a positive role for the development research and practical application of CR, such as common control channel, energy harvesting, non-orthogonal multiple access, and CR based aeronautical communication are discussed. The comprehensive overview provided by this survey is expected to help researchers develop CR technology in the field of 5G further.
A Comparison of GFR Estimation Formulae in Pediatric Oncology

Abstract Background Application of potentially nephrotoxic chemotherapy requires continuous monitoring of renal function for toxicity and dosing. Novel pediatric glomerular filtration rate (GFR) estimating equations including cystatin C have been proposed to enhance the reliability of GFR calculation. Materials and methods We examined a pediatric oncologic data set with a total of 363 GFR measurements. An analysis of distribution characteristics and comparison of medians was performed to compare creatinine and cystatin C-based GFR estimating formulae. Furthermore, we investigated the clinical impact of different equations in regard to therapeutic consequences. Results Significant differences in estimated GFR values were calculated depending on the applied formula (range of median GFR from 94.8 to 180.9 mL/min per 1.73 m2) which may result in different therapeutic consequences for the use of potentially nephrotoxic chemotherapeutic agents. Significant correlation for all examined formulae was identified, however there were large fluctuations among the correlation coefficients ranging from 0.254 to 1.0. Conclusion This study compares proposed pediatric GFR estimating equations in a clinical setting. It underlines the current limitations and difficulties of GFR estimation including potential dosing errors. Cystitis C-based equations can be used as alternatives to creatinine-based estimations when the appropriate laboratory method has been applied. A comparative calculator for pediatric GFR estimating equations along with background information is provided at http://gfr.pedz. de and may support clinical decision-making.
Molecular phylogeny of holothuria (Mertensiothuria) leucospilota (Brandt 1835) as inferred from cytochrome C oxidase I mitochondrial DNA gene sequences

Holothuria (Mertensiothuria) leucospilota (Brandt 1835), white threads fish or locally known as bat puntil is currently considered as the most abundant sea cucumber species in Malaysia. This study aimed to generate the genetic profile of H. leucospilota from Malaysia and then to determine the phylogenetic relationship between H. leucospilota and other members of genus Holothuria using partial sequences of cytochrome c oxidase I (COI) mitochondrial DNA (mtDNA) gene. In this study, specimens of H. leucospilota were collected from Intan Besar Island, Langkawi, Kedah Darul Aman in the west coast of Peninsular Malaysia. Three main methods namely neighbour joining, maximum parsimony and maximum likelihood were used for the phylogenetic tree reconstruction. Tree topologies showed that H. leucospilota has its own monophyletic clade clearly distinct from the other species. The pairwise genetic distance calculated further supported these findings. In addition, the results also should that the COI mtDNA gene is capable to unravel the phylogenetic relationship of H. leucospilota. Keywords: Holothuria leucospilota; molecular systematics; partial sequences of cytochrome oxidase I gene; phylogeny tree
Identification of Common Genes Refers to Colorectal Carcinogenesis with Paired Cancer and Noncancer Samples

Colorectal cancer is a malignant tumor which harmed human beings' health. The aim of this study was to explore common biomarkers associated with colorectal carcinogenesis in paired cancer and noncancer samples. At first, fifty-nine pairs of colorectal cancer and noncancer samples from three gene expression datasets were collected and analyzed. Then, 181 upregulation and 282 downregulation common differential expression genes (DEGs) were found. Next, functional annotation was performed in the DAVID database with the DEGs. Finally, real-time polymerase chain reaction (PCR) assay was conducted to verify the analyses in sixteen colorectal cancer and individual-matched adjacent mucosa samples. Real-time PCR showed that MCM2, RNASEH2A, and TOP2A were upregulated in colorectal cancer compared with adjacent mucosa samples (MCM2, P < 0.001; RNASEH2A, P < 0.001; TOP2A, P = 0.001). These suggested that 463 DEGs might contribute to colorectal carcinogenesis.
Aberrant Rac1-cofilin signaling mediates defects in dendritic spines, synaptic function, and sensory perception in fragile X syndrome

Inhibiting Rac1-PAK-LIMK signaling may restore synaptic function and sensory processing in patients with fragile X syndrome. Rac1-PAK signaling a target for FXS therapy? The inherited intellectual disability and autism-associated disorder fragile X syndrome (FXS) is caused by the loss of the mRNA-binding protein FMRP and characterized by an increased formation, but impaired maturation, of dendritic spines. Spine outgrowth and maturation are dependent on actin polymerization-depolymerization dynamics. Pyronneau et al. found that loss of FMRP in mice increased the abundance and activity of the GTPase Rac1. Rac1 activated the kinases PAK and LIMK1, which inactivated cofilin, thus preventing actin depolymerization dynamics. A pharmacological inhibitor of PAK decreased the number of immature spines and improved sensory processing in FXS model mice, suggesting that targeting this pathway may be therapeutic in patients. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disabilities and a leading cause of autism. FXS is caused by a trinucleotide expansion in the gene FMR1 on the X chromosome. The neuroanatomical hallmark of FXS is an overabundance of immature dendritic spines, a factor thought to underlie synaptic dysfunction and impaired cognition. We showed that aberrantly increased activity of the Rho GTPase Rac1 inhibited the actin-depolymerizing factor cofilin, a major determinant of dendritic spine structure, and caused disease-associated spine abnormalities in the somatosensory cortex of FXS model mice. Increased cofilin phosphorylation and actin polymerization coincided with abnormal dendritic spines and impaired synaptic maturation. Viral delivery of a constitutively active cofilin mutant (cofilinS3A) into the somatosensory cortex of Fmr1-deficient mice rescued the immature dendritic spine phenotype and increased spine density. Inhibition of the Rac1 effector PAK1 with a small-molecule inhibitor rescued cofilin signaling in FXS mice, indicating a causal relationship between PAK1 and cofilin signaling. PAK1 inhibition rescued synaptic signaling (specifically the synaptic ratio of NMDA/AMPA in layer V pyramidal neurons) and improved sensory processing in FXS mice. These findings suggest a causal relationship between increased Rac1-cofilin signaling, synaptic defects, and impaired sensory processing in FXS and uncover a previously unappreciated role for impaired Rac1-cofilin signaling in the aberrant spine morphology and spine density associated with FXS.
CirComPara: A Multi-Method Comparative Bioinformatics Pipeline to Detect and Study circRNAs from RNA-seq Data

Circular RNAs (circRNAs) are generated by back-splicing of immature RNA forming covalently closed loops of intron/exon RNA molecules. Pervasiveness, evolutionary conservation, massive and regulated expression, and post-transcriptional regulatory roles of circRNAs in eukaryotes have been appreciated and described only recently. Moreover, being easily detectable disease markers, circRNAs undoubtedly represent a molecular class with high bearing on molecular pathobiology. CircRNAs can be detected from RNA-seq data using appropriate computational methods to identify the sequence reads spanning back-splice junctions that do not co-linearly map to the reference genome. To this end, several programs were developed and critical assessment of various strategies and tools suggested the combination of at least two methods as good practice to guarantee robust circRNA detection. Here, we present CirComPara (http://github.com/egaffo/CirComPara), an automated bioinformatics pipeline, to detect, quantify and annotate circRNAs from RNA-seq data using in parallel four different methods for back-splice identification. CirComPara also provides quantification of linear RNAs and gene expression, ultimately comparing and correlating circRNA and gene/transcript expression levels. We applied our method to RNA-seq data of monocyte and macrophage samples in relation to haploinsufficiency of the RNA-binding splicing factor Quaking (QKI). The biological relevance of the results, in terms of number, types and variations of circRNAs expressed, illustrates CirComPara potential to enlarge the knowledge of the transcriptome, adding details on the circRNAome, and facilitating further computational and experimental studies.
Optimal Task Recommendation for Mobile Crowdsourcing With Privacy Control

Mobile crowdsourcing (MC) is a transformative paradigm that engages a crowd of mobile users (i.e., workers) in the act of collecting, analyzing, and disseminating information or sharing their resources. To ensure quality of service, MC platforms tend to recommend MC tasks to workers based on their context information extracted from their interactions and smartphone sensors. This raises privacy concerns hard to address due to the constrained resources on mobile devices. In this paper, we identify fundamental tradeoffs among three metrics-utility, privacy, and efficiency-in an MC system and propose a flexible optimization framework that can be adjusted to any desired tradeoff point with joint efforts of MC platform and workers. Since the underlying optimization problems are NP-hard, we present efficient approximation algorithms to solve them. Since worker statistics are needed when tuning the optimization models, we use an efficient aggregation approach to collecting worker feedbacks while providing differential privacy guarantees. Both numerical evaluations and performance analysis are conducted to demonstrate the effectiveness and efficiency of the proposed framework.
Fluctuations in heart rate variability of health care workers during four consecutive extended work shifts and recovery during rest and sleep

The aim of this study was to investigate fluctuations in heart rate variability (HRV), which reflect autonomic nervous system (ANS) function and potential psychological and physical strain, among 24 health care workers during work and sleep during four consecutive extended work shifts. Data included 24/36/12 h of HRV measurements, two logbooks, and a questionnaire. A cross-shift/cross-week design was applied. HRV was measured during work, leisure time, and sleep. The HRV data included time-domain [mean RR, SD of normal to normal R-R intervals (SDNN), and root mean square of the successive differences (RMSSD)] and frequency-domain [low frequency (LF)/high frequency (HF) ratio] parameters. HRV parameters revealed significant differences among work, leisure time, and sleep. Mean RR, RMSSD, and SDNN values were lower and the LF/HF ratio was higher on the first versus last day of the work period; however, the differences were most prominent in the morning hours. The results indicate higher levels of cardiovascular stress on the first versus fourth day of the working period, and measurements at night indicate a satisfactory recovery from the extended shifts.
Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.
Studies of exocytosis at single cells

Keith T. Thornley: Studies of Exocytosis at Single Cells (Under the direction of Dr. R. Mark Wightman) Intercellular communication via chemical signaling is vital to the healthy functioning of multicellular organisms. In exocytosis, intracellular vesicles undergo Ca-triggered fusion with the cell plasma membrane, releasing their chemical messengers into the extracellular space. As exocytosis serves as the primary mechanism of communication at neuronal synapses, great emphasis has been placed on understanding the complex cellular regulation of this process. This dissertation focused on the use of amperometry and fast scan cyclic voltammetry at carbon-fiber microelectrodes to monitor exocytosis in real-time at both isolated neurons and chromaffin cells, well-characterized model cells for neuronal exocytosis. These techniques provide the necessary temporal resolution and sensitivity required to detect the chemical signals resulting from individual vesicular release events. Amperometric recordings at midbrain dopamine neurons showed that somatodendritic dopamine release is exocytotic, with a bimodal distribution of vesicular events. A combinatorial approach was used to demonstrate alterations in biogenic amine exocytosis in mice lacking the mitochondrial uncoupling protein UCP2 or the hormone leptin. Conversely, a mouse model of fragile X syndrome revealed no deficiencies in vesicular release mechanisms. Electrochemical methodologies were developed to distinguish catecholamine transmitters from the L-tyrosine-derived trace amines. Application of these methods revealed poor vesicular accumulation of trace amines precludes their function as false transmitters. Finally, vesicular quantal size in chromaffin cells was shown to be resistant to exogenous application of catecholamine precursors.
Towards fully reflective environments

Modern development environments promote live programming (LP) mechanisms because it enhances the development experience by providing instantaneous feedback and interaction with live objects. LP is typically supported with advanced reflective techniques within dynamic languages. These languages run on top of Virtual Machines (VMs) that are built in a static manner so that most of their components are bound at compile time. As a consequence, VM developers are forced to work using the traditional edit-compile-run cycle, even when they are designing LP-supporting environments. In this paper we explore the idea of bringing LP techniques to the VM domain for improving their observability, evolution and adaptability at run-time. We define the notion of fully reflective execution environments (EEs), systems that provide reflection not only at the application level but also at the level of the VM. We characterize such systems, propose a design, and present Mate v1, a prototypical implementation. Based on our prototype, we analyze the feasibility and applicability of incorporating reflective capabilities into different parts of EEs. Furthermore, the evaluation demonstrates the opportunities such reflective capabilities provide for unanticipated dynamic adaptation scenarios, benefiting thus, a wider range of users.