Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of tivozanib in advanced renal cell carcinoma therapy

ABSTRACT Introduction: The efficacy of VEGF-targeting therapies in clinical trials led to their recommendation in clinical guidelines for use across the advanced or metastatic renal cell carcinoma (RCC) treatment landscape, however, tolerability (including off-target effects) has remained a challenge. Tivozanib is a selective inhibitor of all three VEGFRs, with limited off-target interaction, which demonstrates efficacy with improved tolerability relative to multikinase VEGFR-TKIs. Areas covered: Covered here is the clinical development of tivozanib in advanced RCC, including the pivotal Phase III, multicenter, open-label, randomized clinical study comparing tivozanib with sorafenib for the treatment of VEGF- and mTOR therapy-naïve advanced RCC patients. Also covered are ongoing trials, exploring the efficacy and safety of tivozanib in the setting of refractory disease and the utility of tivozanib in combination with checkpoint inhibitors for advanced RCC. Combination of a VEGFR-TKI and immunotherapy is promising in advanced RCC, if the treatment regimens have acceptable tolerability. Here the selectivity of tivozanib may contribute to an acceptable tolerability profile when used in combination therapy. Expert commentary: The approval of tivozanib provides an additional option for the first-line treatment of advanced or metastatic RCC patients in Europe and allows use of a VEGFR-TKI with selectivity for VEGFRs in this setting.
Duck Attack on Accountable Distributed Systems

Accountability plays a key role in dependable distributed systems. It allows to detect, isolate and churn malicious/selfish nodes that deviate from a prescribed protocol. To achieve these properties, several accountable systems use at their core cryptographic primitives that produce non-repudiable evidence of inconsistent or incorrect behavior. In this paper, we show how selfish and colluding nodes can exploit the use of cryptographic digests in accountability protocols to mount what we call a duck attack. In a duck attack, selfish and colluding nodes exploit the use of cryptographic digests to alter the transmission of messages while masquerading as honest entities. The end result is that their selfish behavior remains undetected. This undermines the security guarantees of the accountability protocols. We first discover the duck attack while analyzing PAG --- a custom cryptographic protocol to build accountable systems presented at ICDCS 2016. We later discover that accountable distributed systems based on a secure log (essentially a hash-based data structure) are also vulnerable to the duck attack and apply it on AcTinG --- a protocol presented at SRDS 2014. To defeat our attack, we modify the underlying secure log to have high-order dependency on the messages stored in it.
The Evolution of the Industry 4.0: A Retrospective Analysis Using Text Mining

Industry 4.0 and its applications have attracted the interest of both experts of industry and researchers of academy. This interest started to build a vast body of literature on the related topics and caused to raise a new question about how the related literature has changed over time. In this context, the major objective of the presented study is to provide insight about the scientific researches on industry 4.0 using the publications from the Thomson Reuters Web of Knowledge database during the period of 2007-2017. For this aim, the retrieved academic studies were analyzed using quantitative and text mining analyses to observe the change in number of publications over years and to gain insight about the textual structure. The results of the quantitative analysis showed that the popularity of industry 4.0 in the academy has risen significantly and reached the peak point in 2017 with 2658 articles. According to the text mining study, the most important research topics related to the industry 4.0 field are "mobile", "internet of things" and "cloud computing".
Prevalence and prediction of higher estimated gastric content in parturients at full cervical dilatation: A prospective cohort study

Emergent obstetrical procedures may require general anaesthesia in parturients at full cervical dilatation or immediately after vaginal birth. This study aimed to determine the prevalence and the predictive factors of higher estimated gastric content in parturients at full cervical dilatation with epidural analgesia and allowed to drink during the labour, and to assess the ability of the antral area measured in the semirecumbent position (SR‐CSA) to identify higher estimated gastric content in this setting.
Revisiting the simulation of quantum Turing machines by quantum circuits

Yao's 1995 publication ‘Quantum circuit complexity’ in Proceedings of the 34th Annual IEEE Symposium on Foundations of Computer Science, pp. 352–361, proved that quantum Turing machines and quantum circuits are polynomially equivalent computational models: t≥n steps of a quantum Turing machine running on an input of length n can be simulated by a uniformly generated family of quantum circuits with size quadratic in t, and a polynomial-time uniformly generated family of quantum circuits can be simulated by a quantum Turing machine running in polynomial time. We revisit the simulation of quantum Turing machines with uniformly generated quantum circuits, which is the more challenging of the two simulation tasks, and present a variation on the simulation method employed by Yao together with an analysis of it. This analysis reveals that the simulation of quantum Turing machines can be performed by quantum circuits having depth linear in t, rather than quadratic depth, and can be extended to variants of quantum Turing machines, such as ones having multi-dimensional tapes. Our analysis is based on an extension of method described by Arright, Nesme and Werner in 2011 in Journal of Computer and System Sciences 77, 372–378. (doi:10.1016/j.jcss.2010.05.004), that allows for the localization of causal unitary evolutions.
ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation

Abstract The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in gene expression, is being increasingly appreciated. ZBTB24, a poorly characterized zinc-finger protein, or the de novo methyltransferase DNMT3B, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting an underlying mechanistic link. Chromatin immunoprecipitation coupled with loss-of-function approaches in model systems revealed common loci bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function. We identify a ZBTB24 DNA binding motif, which is contained within the promoters of most of its transcriptional targets, including CDCA7, AXIN2, and OSTC. Direct binding of ZBTB24 at the promoters of these genes targets them for transcriptional activation. ZBTB24 binding at the promoters of RNF169 and CAMKMT, however, targets them for transcriptional repression. The involvement of ZBTB24 targets in diverse cellular programs, including the VDR/RXR and interferon regulatory pathways, suggest that ZBTB24’s role as a transcriptional regulator is not restricted to immune cells.
Hodge decomposition of wall shear stress vector fields characterizing biological flows

A discrete boundary-sensitive Hodge decomposition is proposed as a central tool for the analysis of wall shear stress (WSS) vector fields in aortic blood flows. The method is based on novel results for the smooth and discrete Hodge–Morrey–Friedrichs decomposition on manifolds with boundary and subdivides the WSS vector field into five components: gradient (curl-free), co-gradient (divergence-free) and three harmonic fields induced from the boundary, which are called the centre, Neumann and Dirichlet fields. First, an analysis of WSS in several simulated simplified phantom geometries (duct and idealized aorta) was performed in order to understand the nature of the five components. It was shown that the decomposition is able to distinguish harmonic blood flow arising from the inlet from harmonic circulations induced by the interior topology of the geometry. Finally, a comparative analysis of 11 patients with coarctation of the aorta (CoA) before and after treatment as well as 10 control patients was done. The study shows a significant difference between the CoA patients before and after the treatment, and the healthy controls. This means a global difference between aortic shapes of diseased and healthy subjects, thus leading to a new type of WSS-based analysis and classification of pathological and physiological blood flow.
Hapcube: a tactile actuator providing tangential and normal pseudo-force feedback on a fingertip

We developed a tactile actuator named HapCube that provides tangential and normal pseudo-force feedback on user's fingertip. The tangential feedback is generated by synthesizing two orthogonal asymmetric vibrations, and it simulates frictional force in any desired tangential directions. The normal feedback simulates tactile sensations when pressing various types of button. In addition, by combining the two feedbacks, it can produce frictional force and surface texture simultaneously.
Structural and functional effects of myosin-binding protein-C phosphorylation in heart muscle are not mimicked by serine-to-aspartate substitutions

Myosin-binding protein-C (cMyBP-C) is a key regulator of contractility in heart muscle, and its regulatory function is controlled in turn by phosphorylation of multiple serines in its m-domain. The structural and functional effects of m-domain phosphorylation have often been inferred from those of the corresponding serine-to-aspartate (Ser–Asp) substitutions, in both in vivo and in vitro studies. Here, using a combination of in vitro binding assays and in situ structural and functional assays in ventricular trabeculae of rat heart and the expressed C1mC2 region of cMyBP-C, containing the m-domain flanked by domains C1 and C2, we tested whether these substitutions do in fact mimic the effects of phosphorylation. In situ changes in thin and thick filament structure were determined from changes in polarized fluorescence from bifunctional probes attached to troponin C or myosin regulatory light chain, respectively. We show that both the action of exogenous C1mC2 to activate contraction in the absence of calcium and the accompanying change in thin filament structure are abolished by tris-phosphorylation of the m-domain, but unaffected by the corresponding Ser–Asp substitutions. The latter produced an intermediate change in thick filament structure. Both tris-phosphorylation and Ser–Asp substitutions abolished the interaction between C1mC2 and myosin sub-fragment 2 (myosin S2) in vitro, but yielded different effects on thin filament binding. These results suggest that some previous inferences from the effects of Ser–Asp substitutions in cMyBP-C should be reconsidered and that the distinct effects of tris-phosphorylation and Ser–Asp substitutions on cMyBP-C may provide a useful basis for future studies.
HiPS: Hierarchical Parameter Synchronization in Large-Scale Distributed Machine Learning

In large-scale distributed machine learning (DML) system, parameter (gradient) synchronization among machines plays an important role in improving the DML performance. State-of-the-art DML synchronization algorithms, either the parameter server (PS) based algorithm or the ring allreduce algorithm, work in a flat way and suffer when the network size is large. In this work, we propose HiPS, a hierarchical parameter (gradient) synchronization framework in large-scale DML. In HiPS, server-centric network topology is used to better embrace RDMA/RoCE transport between machines, and the parameters (gradients) are synchronized in a hierarchical and hybrid way. Our evaluation in BCube and Torus network demonstrates that HiPS can better match server-centric networks. Compared with the flat algorithms (PS-based and ring-based), HiPS reduces the synchronization time by 73% and 75% respectively.
Development of Paper-Based Analytical Devices for Minimizing the Viscosity Effect in Human Saliva

Rationale: Saliva as a sample matrix is rapidly gaining interest for disease diagnosis and point-of-care assays because it is easy to collect (non-invasive) and contains many health-related biomarkers. However, saliva poses particular problems relative to more common urine and blood matrices, which includes low analyte concentrations, lack of understanding of biomolecule transportation and inherent viscosity variability in human samples. While several studies have sought to improve assay sensitivity, few have addressed sample viscosity specifically. The goal of this study is to minimize the effect of sample viscosity on paper-based analytical devices (PADs) for the measurement of pH and nitrite in human saliva. Methods: PADs were used to measure salivary pH from 5.0 to 10.0 with a universal indicator consisting of chlorophenol red, phenol red and phenolphthalein. Nitrite determination was performed using the Griess reaction. Artificial saliva with viscosity values between 1.54 and 5.10 mPa∙s was tested on the proposed PAD. To ensure the proposed PADs can be tailored for use in-field analysis, the devices were shipped to Australia and tested with human specimens. Results: Initial experiments showed that viscosity had a significant impact on the calibration curve for nitrite; however, a more consistent curve could be generated when buffer was added after the sample, irrespective of sample viscosity. The linear range for nitrite detection was 0.1 to 2.4 mg/dL using the improved method. The nitrite measurement in artificial saliva also showed a good correlation with the standard spectrophotometry method (p=0.8484, paired sample t-test, n=20). Measured pH values from samples with varying viscosities correlated well with the results from our pH meter. Conclusions: The inherent variation of salivary viscosity that impacts nitrite and pH results can be addressed using a simple washing step on the PAD without the need for complex procedures.
Designing Digital Interactive Instructions for Children's Construction Play

Although digital interactive technology offers innovative, scarcely explored types of instruction, conventional analog paper booklets remain the main instruction format for children's construction play. We examined how a fan-built, digital interactive instructions prototype affected children's construction play compared to an analog booklet. We studied two LEGO building tasks among 20 eight-nine year-old boys. Ten used the prototype on an iPad, 10 the booklet. Using a quasi-experimental research design built on cognitive load theory, we found notable differences in the two construction play processes. Participants with the analog booklet had a faster, more fluent process, while the digital prototype group was more often distracted and seeking help. We propose basic design recommendations for digital interactive instructions for children's construction play, i.e., include a rotational feature, animations, pace control, few buttons, and realistic colors.
SN-FFC: Improving Survivability of LEO Satellite Network with Forward Fault Correction

Low Earth Orbit (LEO) Satellite network will suffer from heavy congestion under network faults such as node failure, which affects its survivability. Traffic engineering is the mechanism to solve such problem. In data-center wide area networks (DCWAN), Forward Fault Correction (FFC), a proactive traffic engineering system, can ensure that the network is free from congestion as long as the number of faults is up to k. Inspired by FFC, we implement SN-FFC in LEO satellite network. We show how SN-FFC can transmit data flows normally in the case of node failures. Our simulation results show that the LEO satellite network and the DCWAN have certain similarities in the fault-tolerance mechanism based on traffic engineering with FFC. Therefore, it can guide us to do more in-depth research in this area.
A 3D Advancing-Front Delaunay Mesh Refinement Algorithm

I present a 3D advancing-front mesh refinement algorithm that generates a constrained Delaunay mesh for any piecewise linear complex (PLC) and extend this algorithm to produce truly Delaunay meshes for any PLC. First, as in my recently published 2D algorithm, I split the input line segments such that the length of the subsegments is asymptotically proportional to the local feature size (LFS). For each facet, I refine the mesh such that the edge lengths and the radius of the circumcircle of every triangular element are asymptotically proportional to the LFS. Finally, I refine the volume mesh to produce a constrained Delaunay mesh whose tetrahedral elements are well graded and have a radius-edge ratio less than some $\omega^*>2/\sqrt{3}$ (except ``near'' small input angles). I extend this algorithm to generate truly Delaunay meshes by ensuring that every triangular element on a facet satisfies Gabriel's condition, i.e., its diametral sphere is empty. On an ``apex'' vertex where multiple facets intersect, Gabriel's condition is satisfied by a modified split-on-a-sphere (SOS) technique. On a line where multiple facets intersect, Gabriel's condition is satisfied by mirroring meshes near the line of intersection. The SOS technique ensures that the triangles on a facet near the apex vertex have angles that are proportional to the angular feature size (AFS), a term I define in the paper. All tetrahedra (except ``near'' small input angles) are well graded and have a radius-edge ratio less than $\omega^*>\sqrt{2}$ for a truly Delaunay mesh. The upper bounds for the radius-edge ratio are an improvement by a factor of $\sqrt{2}$ over current state-of-the-art algorithms.
Facile Ag-Film Based Surface Enhanced Raman Spectroscopy Using DNA Molecular Switch for Ultra-Sensitive Mercury Ions Detection

Heavy metal pollution has long been the focus of attention because of its serious threat to human health and the environment. Surface enhanced Raman spectroscopy (SERS) has shown great potential for metal detection owing to many advantages, including, requiring fewer samples, its minimal damage to specimen, and its high sensitivity. In this work, we proposed a simple and distinctive method, based on SERS, using facile silver film (Ag-film) combined with a DNA molecular switch, which allowed for the highly specific detection of heavy metal mercury ions (Hg2+). When in the presence of Hg2+ ions, the signals from Raman probes attach to single-stranded DNA, which will be dramatically enhanced due to the specific structural change of DNA strands—resulting from the interaction between Hg2+ ions and DNA bases. This SERS sensor could achieve an ultralow limit of detection (1.35 × 10−15 M) for Hg2+ detection. In addition, we applied this SERS sensor to detect Hg2+ in real blood samples. The results suggested that this SERS platform could be a promising alternative tool for Hg2+ detection in clinical, environmental, and food inspection.
Endoscopic submucosal dissection of malignant non-pedunculated colorectal lesions

Background and study aims Endoscopic submucosal dissection (ESD) is an established method for en bloc resection of large non-pedunculated colorectal lesions in Asia but dissemination of ESD in Western countries is limited. The aim of this study was to evaluate the role of ESD in the management of malignant non-pedunculated colorectal lesions in a European center. Patients and methods Among 255 patients undergoing colorectal ESD between 2014 and 2016, 29 cases were identified as submucosal invasive cancers and included in this study. The main outcomes were en bloc, R0 and curative resection as well as procedural time, complications and recurrence. Results Median tumor size was 40 mm (range 20 – 70 mm). Thirteen cancers were located in the colon and 16 were located in the rectum. Procedural time was 89 minutes (range 18 – 594 minutes). Complete resection was achieved in 28 cases, en bloc and R0 resection rates were 83 % and 69 %, respectively. Curative resection rate was 38 %. One case had a perforation in the sigmoid colon requiring emergency surgery. No significant bleeding occurred. Six patients underwent additional surgery after ESD, one of whom had residual tumor. One recurrence was detected in 20 patients that were followed-up endoscopically, median follow-up time was 13 months (range 2 – 30 months). Conclusion ESD seems to be a safe and effective method for treating non-pedunculated malignant colorectal lesions after careful patient selection and proper endoscopic training.
Smart Streaming of Panoramic Videos

The streaming of panoramic videos comes with a new challenge: adapting the streamed content to user attention. In this paper, by making some abstraction we study the key issues of the problem: (1) online content switching strategies, and (2) offline segmentation in preparation for adaptive streaming. Our work demonstrates how the problem depends fundamentally on user behavior, represented by user attention trajectories. Although we only relied on a typical real-world measured trajectory and two artificially generated benchmark trajectories, we point out how more knowledge of user attention can help optimize both the online and offline strategies.
The Effects of Vitamin D Supplementation on Markers Related to Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract This systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to summarize the effect of vitamin D supplementation on endothelial function among people with metabolic syndrome and related disorders. Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related RCTs published up 20th May 2018. To check heterogeneity a Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary effect size. Twenty-two trials of 931 potential citations were found to be eligible for current meta-analysis. The pooled findings by using random effects model indicated that vitamin D supplementation to individuals with MetS and related disorders significantly increased flow-mediated dilatation (FMD) (SMD=1.10; 95% CI, 0.38, 1.81, p=0.003). However, it did not affect pulse-wave velocity (PWV) (SMD=0.04; 95% CI, –0.25, 0.33, p=0.80) and augmentation index (AI) (SMD=0.07; 95% CI, –0.25, 0.40; p=0.65). Overall, this meta-analysis demonstrated that vitamin D supplementation to patients with metabolic syndrome and related disorders resulted in an improvement in FMD, but did not influence PWV and AI.