Miracle-dz/UniFAR-FTUs huggingface dataset:
Amorphous silica nanoparticles induce tumorigenesis via regulating ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation

Background Recent studies indicate amorphous silica nanoparticles (SiNPs), one of the widely applied nanomaterials, have potential toxicity in humans and induces cell malignant transformation. However, its carcinogenic mechanisms remain poorly understood. This study’s purpose was to investigate the underlying toxic mechanisms of amorphous SiNPs on human lung epithelial cells model by using microarray data. Methods Microarray dataset GSE82062 was collected from Gene Expression Omnibus database, including three repeats of Beas-2B exposed to amorphous SiNPs for 40 passages and three repeats of passage-matched control Beas-2B cells. Differentially expressed genes (DEGs) were identified using linear models for microarray data method. Protein–protein interaction (PPI) network was constructed using data from the STRING database followed by module analysis. The miRwalk2 database was used to predict the underlying target genes of differentially miRNAs. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. Results A total of 323 genes were identified as DEGs, including 280 downregulated (containing 12 pre-miRNAs) and 43 upregulated genes (containing 29 pre-miRNAs). Function enrichment indicated these genes were involved in translational initiation (i.e., eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), poly (A) binding protein cytoplasmic 1 (PABPC1)), response to reactive oxygen species (i.e., superoxide dismutase 1 (SOD1)) and oxidative phosphorylation (i.e., ATP5H). PABPC1 (degree = 15), ATP5H (degree = 11) and SOD1 (degree = 8)] were proved to be hub genes after PPI-module analyses. ATP5H/SOD1 and EIF4G2/PABPC1 were overlapped with the target genes of differentially expressed pre-miR-3648/572/661 and pre-miR-4521. Conclusions Amorphous SiNPs may induce tumorigenesis via influencing ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation which may be regulated by miR-3648/572/661 and miR-4521, respectively.
Optimal postoperative adjuvant treatment strategy for HBV-related hepatocellular carcinoma with microvascular invasion: a propensity score analysis

Background Microvascular invasion (MVI) is the most important risk factor associated with early postoperative recurrence in patients with hepatocellular carcinoma (HCC). However, the efficacy of postoperative adjuvant treatment for preventing recurrence in HCC patients with MVI has not been assessed. This study investigated the efficacy of postoperative adjuvant radiotherapy (RT) and transcatheter arterial chemoembolization (TACE) in HCC patients with MVI. Materials and methods From July 2008 to December 2016, 117 hepatitis B virus (HBV)-related HCC patients with MVI were retrospectively divided into two groups based on postoperative adjuvant treatments. Propensity score matching (PSM) was performed to adjust for significant differences in baseline characteristics. Relapse-free survival (RFS) and overall survival (OS) of the two groups were analyzed before and after PSM. Results Of all patients, the RT group had significantly smaller tumor size and milder MVI classification. PSM analysis created 46 pairs of patients. After matching, the two groups of patients were similar in baseline characteristics. Multivariate analysis indicated that tumor size, MVI classification, and postoperative treatment strategies were independently associated with RFS; tumor size and MVI classification were independently associated with OS. Similar multivariate analysis results were demonstrated after matching propensity score. Survival analysis revealed that the estimated median RFS and OS of patients with RT and TACE were 25.74±8.12 vs 9.18±1.67 months (P=0.003) and 60.69±7.36 vs 36.53±5.34 months (P=0.262), respectively. The RT group had significantly longer RFS than the TACE group. Conclusion Postoperative adjuvant RT offers better RFS for HCC patients with MVI than TACE.
Contactless Monitoring of Critical Infrastructure [From the Guest Editors]

Industrial control systems (ICSs) manage and monitor critical civil or military infrastructure, such as water treatment facilities, power plants, electricity grids, transportation systems, oil and gas refineries, and health care. Because they are so important, ICSs are becoming attractive targets for malicious attacks that could lead to catastrophic failures with substantive impacts. Among such attacks was the BlackEnergy worm [1], which was used in 2015 against the Ukrainian electricity grid, resulting in widespread power outages, and the Stuxnet malware [2], which was used in 2010 and physically damaged 20% of the Iranian centrifuges controlled by programmable logic controllers (PLCs). New security concerns arise as the public adopts Internet of Things (IoT) devices, resulting in household electronics becoming computers that can be targets for malware. Over the last few years, Internet-connected appliances, home routers, webcams, and printers were used to launch distributed denial-of-service (DDoS) attacks, often without their owners' knowledge. The largest DDoS attack to target IoT devices was in 2016, when a botnet malware family named Mirai was launched [3]. IoT devices are attractive targets for malware because they lack cryptographic encryption and strong default authentication.
IskiOS: Lightweight Defense Against Kernel-Level Code-Reuse Attacks

Commodity operating systems such as Windows, Linux, and MacOS X form the Trusted Computing Base (TCB) of today's computing systems. However, since they are written in C and C++, they have memory safety errors and are vulnerable to kernel-level code reuse attacks. This paper presents IskiOS: a system that helps to thwart such attacks by providing both execute-only memory and an efficient shadow stack for operating system kernels on the x86 processor. Execute-only memory hides the code segment from buffer overread attacks, strengthening code randomization techniques. Shadow stacks protect return addresses from corruption. IskiOS leverages Intel's Memory Protection Keys (MPK, a.k.a. PKU) and Kernel Page Table Isolation (KPTI) to protect kernel memory from buffer overwrite and overread attacks and to prevent corruption of the shadow stack. Unlike previous work, IskiOS places no restrictions on virtual address space layout, allowing the operating system to achieve higher diversification entropy by placing kernel stacks and kernel code in arbitrary locations within the virtual address space. IskiOS incurs virtually no performance overhead for execute-only memory. Its shadow stacks incur a geometric mean slowdown of 12.3% in our experiments.
Non-REM Sleep Characteristics Predict Early Cognitive Impairment in an Aging Population

Objective: Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults. Methods: This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night. Results: Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, P < 0.05), theta power (OR 0.018, P < 0.01), sigma power (OR 0.033, P < 0.05), and spindle maximal amplitude (OR 0.002, P < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment (P < 0.05). Conclusion: A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.
Continuous Program Optimization via Advanced Dynamic Compilation Techniques

In High Performance Computing, it is often useful to fine tune an application code via recompilation of specific computational intensive code fragments to leverage runtime knowledge. Traditional compilers rarely provide such capabilities, while solutions such as LIBVC allow C/C++ code to employ dynamic compilation. We evaluate the impact of the introduction of Just-in-Time (JIT) compilation in a framework supporting partial dynamic (re-) compilation of functions to provide continuous optimization in high performance environments. We show that JIT solutions can have comparable performance in terms of code quality and smaller compilation overhead w.r. t. the LIBVC alternatives. We further demonstrate the strength of our approach against a state-of-the-art interpreter-based dynamic evaluation solution.
Biopolymers for Biomedical and Pharmaceutical Applications: Recent Advances and Overview of Alginate Electrospinning

Innovative solutions using biopolymer-based materials made of several constituents seems to be particularly attractive for packaging in biomedical and pharmaceutical applications. In this direction, some progress has been made in extending use of the electrospinning process towards fiber formation based on biopolymers and organic compounds for the preparation of novel packaging materials. Electrospinning can be used to create nanofiber mats characterized by high purity of the material, which can be used to create active and modern biomedical and pharmaceutical packaging. Intelligent medical and biomedical packaging with the use of polymers is a broadly and rapidly growing field of interest for industries and academia. Among various polymers, alginate has found many applications in the food sector, biomedicine, and packaging. For example, in drug delivery systems, a mesh made of nanofibres produced by the electrospinning method is highly desired. Electrospinning for biomedicine is based on the use of biopolymers and natural substances, along with the combination of drugs (such as naproxen, sulfikoxazol) and essential oils with antibacterial properties (such as tocopherol, eugenol). This is a striking method due to the ability of producing nanoscale materials and structures of exceptional quality, allowing the substances to be encapsulated and the drugs/biologically active substances placed on polymer nanofibers. So, in this article we briefly summarize the recent advances on electrospinning of biopolymers with particular emphasis on usage of Alginate for biomedical and pharmaceutical applications.
Cytotoxic impact of a perillyl alcohol–temozolomide conjugate, NEO212, on cutaneous T-cell lymphoma in vitro

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes of primary cutaneous lymphomas and represent complex diseases regarding their physiopathology and management. Depending on the stage of the disease, different treatment regimens are applied, but there is no consensus on an optimal approach. Prognosis for patients with early stage MF is favorable, but significantly worsens in advanced disease and in SS, where patients frequently relapse and require multiple therapies. Methods: We investigated the potential anticancer effects of NEO212, a novel compound generated by covalently conjugating perillyl alcohol (a natural monoterpene) to temozolomide (an alkylating agent), on MF and SS cell lines in vitro. HUT-78, HUT-102, and MyLa cells were treated with NEO212 under different conditions, and drug effects on proliferation, viability, and apoptosis were characterized. Results: NEO212 inhibited proliferation, diminished viability, and stimulated apoptosis in all cell lines, although with varying degrees of potency in the different cell lines. It down-regulated c-myc and cyclin D1 proteins, which are required for cell proliferation, but triggered endoplasmic reticulum stress and activation of caspases. Pretreatment of cells with antioxidants ascorbic acid and beta-mercaptoethanol prevented these NEO212-induced effects. Conclusions: NEO212 exerted promising anticancer effects on SS and MF cell lines. The generation of reactive oxygen species (ROS) appears to play a key role in the NEO212-induced cell death process, because the blockage of ROS with antioxidants prevented caspase activation. We propose that NEO212 should be investigated further toward clinical testing in these tumor types.
A New Variant of the Winternitz One Time Signature Scheme Based on Graded Encoding Schemes

The Winternitz one-time signature (WOTS) scheme, which can be described using a certain number of so-called “function chains”, plays an important role in the design of both stateless and stateful many-time signature schemes. This work introduces WOTS, a new WOTS type signature scheme in which the need for computing all of the intermediate values of the chains is eliminated. This significantly reduces the number of required operations needed to calculate the algorithms of WOTS. To achieve this results, we have used the concept of “leveled” multilinear maps which is also referred to as graded encoding schemes. In the context of provable security, we reduce the hardness of graded discrete-logarithm (GDL) problem to the EU-CMA security of WOTS in the standard model.
Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety‐like behavior

Social hierarchies are crucial for a group's survival and can influence the way an individual behaves and relates to a given social context. The study of social rank has been classically based on ethological and observational paradigms, but it recently has taken advantage of the use of other approaches, such as the tube test that measures territorial dominance without the display of in situ aggression and is executable in group‐living animals. However, little is known about how previous basal individual differences affect the development of dominance hierarchy measured in the tube test. We have analyzed in male mice body weight, locomotion, anxiety, and serum corticosterone both before and after the tube test, as well as adult hippocampal neurogenesis and transcriptome in the prefrontal cortex after the hierarchy had been established. We found differential gene expression between dominants and subordinates but no association between the other parameters and social status, neither pre‐ nor posttest. Our findings reveal that social rank in mice is stable along time and is not related to basal differences in stress, mood, or physical features. Lastly, real‐time quantitative PCR analysis confirmed differential expression of vomeronasal and olfactory receptors in the cerebral cortex between dominant and subordinate individuals, suggesting that differential brain gene expression in the medial prefrontal cortex could potentially be used as a biomarker of social dominance. —Pallé, A. , Zorzo, C. , Luskey, V. E. , McGreevy, K. R. , Fernandez, S. , Trejo, J. L. Social dominance differentially alters gene expression in the medial prefrontal cortex without affecting adult hippocampal neurogenesis or stress and anxiety‐like behavior. FASEB J. 33, 6995–7008 (2019). www.fasebj. org
Static Analysis of ROP Code

Recent years have witnessed code reuse techniques being employed to craft entire programs such as Jekyll apps, malware droppers, and persistent data-only rootkits. The increased complexity observed in such payloads calls for specific techniques and tools that can help in their analysis. In this paper we propose novel ideas for static analysis of ROP code and apply them to study prominent payloads targeting the Windows platform. Unlike state-of-the-art approaches, we do not require the ROP activation context be reproduced for the analysis. We then propose a guessing mechanism to identify gadget sources for payloads found in documents or over the network.
Hunting the Pertinency of Bloom Filter in Computer Networking and Beyond: A Survey

Bloom filter is a probabilistic data structure to filter a membership of a set. Bloom filter returns “true” or “false” with an error tolerance depending on the presence of the element in the set. Bloom filter is used to boost up the performance of a system using small space overhead. It is extensively used since its inception. The Bloom filter has met wide area of applications. Bloom filter is used in entire computing field irrespective of application and research domain. Bloom filter poses (i) high adaptability, (ii) low memory space overhead as compared to hashing algorithms, (iii) high scalability, and (iv) high performance. In this article, we uncover the application area of Bloom filter in computer networking and its related domain.
Association of Race/Ethnicity, Stage, and Survival in Oral Cavity Squamous Cell Carcinoma: A SEER Study

Objective Survival differences in oral cancer between black and white patients have been reported, but the contributing factors, especially the role of stage, are incompletely understood. Furthermore, the outcomes for Hispanic and Asian patients have been scarcely examined. Study Design Retrospective, population-based national study. Setting Surveillance, Epidemiology, and End Results 18 Custom database (January 1, 2010, to December 31, 2014). Subjects and Methods In total, 7630 patients with primary squamous cell carcinoma in the oral cavity were classified as non-Hispanic white (white), non-Hispanic black (black), Hispanic, or Asian. Cox regression was used to obtain unadjusted and adjusted hazard ratios (HRs) of 5-year mortality for race/ethnicity with sequential adjustments for stage and other covariates. Logistic regression was used to examine the relationship between race/ethnicity and stage with adjusted odds ratios (aORs). Results The cohort consisted of 75.0% whites, 7.6% blacks, 9.1% Hispanics, and 8.3% Asians. Compared to whites, the unadjusted HR for all-cause mortality for blacks was 1.68 (P < .001), which attenuated to 1.15 (P = .039) after adjusting for stage and became insignificant after including insurance. The unadjusted HRs for all-cause mortality were not significant for Hispanics and Asians vs whites. Compared to whites, blacks and Hispanics were more likely to present at later stages (aORs of 2.63 and 1.42, P < .001, respectively). Conclusion The greater mortality for blacks vs whites was largely attributable to the higher prevalence of later stages at presentation and being uninsured among blacks. There was no statistically significant difference in mortality for Hispanics vs whites or Asians vs whites.
The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor β signaling

Neuronal regeneration is a highly energy‐demanding process that greatly relies on axonal mitochondrial transport to meet the enhanced metabolic requirements. Mature neurons typically fail to regenerate after injury, partly because of mitochondrial motility and energy deficits in injured axons. Retinoic acid receptor (RAR)‐β signaling is involved in axonal and neurite regeneration. Here we investigate the effect of RAR‐β signaling on mitochondrial trafficking during neurite outgrowth and find that it enhances their proliferation, speed, and movement toward the growing end of the neuron via hypoxia‐inducible factor 1α signaling. We also show that RAR‐β signaling promotes the binding of the mitochondria to the anchoring protein, glucose‐related protein 75, at the growing tip of neurite, thus allowing them to provide energy and metabolic roles required for neurite outgrowth. —Trigo, D. , Goncalves, M. B. , Corcoran, J. P. T. The regulation of mitochondrial dynamics in neurite outgrowth by retinoic acid receptor β signaling. FASEB J. 33, 7225–7235 (2019). www.fasebj. org
In Silico Molecular Docking and In Vivo Validation with Caenorhabditis elegans to Discover Molecular Initiating Events in Adverse Outcome Pathway Framework: Case Study on Endocrine-Disrupting Chemicals with Estrogen and Androgen Receptors

Molecular docking is used to analyze structural complexes of a target with its ligand for understanding the chemical and structural basis of target specificity. This method has the potential to be applied for discovering molecular initiating events (MIEs) in the Adverse Outcome Pathway framework. In this study, we aimed to develop in silico–in vivo combined approach as a tool for identifying potential MIEs. We used environmental chemicals from Tox21 database to identify potential endocrine-disrupting chemicals (EDCs) through molecular docking simulation, using estrogen receptor (ER), androgen receptor (AR) and their homology models in the nematode Caenorhabditis elegans (NHR-14 and NHR-69, respectively). In vivo validation was conducted on the selected EDCs with C. elegans reproductive toxicity assay using wildtype N2, nhr-14, and nhr-69 loss-of-function mutant strains. The chemicals showed high binding affinity to tested receptors and showed the high in vivo reproductive toxicity, and this was further confirmed using the mutant strains. The present study demonstrates that the binding affinity from the molecular docking potentially correlates with in vivo toxicity. These results prove that our in silico–in vivo combined approach has the potential to be applied for identifying MIEs. This study also suggests the potential of C. elegans as useful in the in vivo model for validating the in silico approach.
A fuzzy formal concept analysis-based approach to uncovering spatial hierarchies among vague places extracted from user-generated data

ABSTRACT The spatial hierarchy of part-whole relationships is an essential characteristic of the platial world. Constructing spatial hierarchies of places is valuable in association analysis and qualitative spatial reasoning. The emergence of large amounts of geotagged user-generated content provides strong support for modelling places. However, the vague nature of places and the complex spatial relationships among places make it intractable to understand and represent the hierarchies among places. In this paper, we introduce a fuzzy formal concept analysis-based approach to uncovering the spatial hierarchies among vague places. Each place is represented as a concept that consists of its extent and its intent. Based on the place concepts, the spatial hierarchies are generated and expressed as a graph that is easy to comprehend and contains abundant information on spatial relations. We also demonstrate the rationality of our result by comparing it with the result of a questionnaire survey.