Miracle-dz/UniFAR-FTUs huggingface dataset:
“Get the Balance Right”: Pathological Significance of Autophagy Perturbation in Neuromuscular Disorders

Recent research has revealed that autophagy, a major catabolic process in cells, is dysregulated in several neuromuscular diseases and contributes to the muscle wasting caused by non-muscle disorders (e.g. cancer cachexia) or during aging (i.e. sarcopenia). From there, the idea arose to interfere with autophagy or manipulate its regulatory signalling to help restore muscle homeostasis and attenuate disease progression. The major difficulty for the development of therapeutic strategies is to restore a balanced autophagic flux, due to the dynamic nature of autophagy. Thus, it is essential to better understand the mechanisms and identify the signalling pathways at play in the control of autophagy in skeletal muscle. A comprehensive analysis of the autophagic flux and of the causes of its dysregulation is required to assess the pathogenic role of autophagy in diseased muscle. Furthermore, it is essential that experiments distinguish between primary dysregulation of autophagy (prior to disease onset) and impairments as a consequence of the pathology. Of note, in most muscle disorders, autophagy perturbation is not caused by genetic modification of an autophagy-related protein, but rather through indirect alteration of regulatory signalling or lysosomal function. In this review, we will present the mechanisms involved in autophagy, and those ensuring its tight regulation in skeletal muscle. We will then discuss as to how autophagy dysregulation contributes to the pathogenesis of neuromuscular disorders and possible ways to interfere with this process to limit disease progression.
Clopidogrel resistance and the effect of combination cilostazol in patients with ischemic stroke or carotid artery stenting using the VerifyNow P2Y12 Assay.

OBJECTIVE The inhibitory response to clopidogrel considerably varies among individuals and clopidogrel resistance is a risk factor for thrombotic events in patients with cardiovascular disease. Based on the platelet aggregation evaluated by the VerifyNow P2Y12 Assay, the present study investigated clopidogrel resistance and the effect of cilostazol addition. METHODS We measured the ability of 20 µM ADP to aggregate platelets using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as % inhibition of <20% in this assay. PATIENTS We examined 77 patients (53 men and 24 women, aged 65.8 ± 9.9 years) with ischemic stroke or carotid artery stenting who received clopidogrel (75 mg) for >7 days at our hospital between October 2009 and March 2010. For 62 patients (42 men and 20 women, aged 65.3 ± 9.9 years) 75 mg clopidogrel alone was administered (clopidogrel only group); the other 15 patients (11 men and 4 women, aged 67.9 ± 9.9 years) received 75 mg of clopidogrel plus 100 or 200 mg of cilostazol (cilostazol combination group). RESULTS Clopidogrel resistance was identified in 18 (29%) of the 62 patients in the clopidogrel only group. The percent inhibition was significantly higher in the cilostazol combination group than in the clopidogrel only group (41.7 ± 28.0% vs. 64.9 ± 22.7%, p=0.005). None of the patients in the cilostazol combination group had % inhibition of <20%. CONCLUSION Clopidogrel resistance developed in 29% of patients given clopidogrel alone. The addition of cilostazol to clopidogrel may have intensified platelet inhibition.
Solomon W. Golomb—Mathematician, Engineer, and Pioneer

In this paper, we present some fundamental concepts and theoretical advances attributable to Solomon Golomb, together with the history and applications of this paper to communications, coding, and cryptography, along with some long-standing conjectures. Examples include the first engineering problem relating to feedback shift-register sequences that Sol Golomb was asked to solve in the mid-1950s. This paper covers <inline-formula> <tex-math notation="LaTeX">$m$ </tex-math></inline-formula>-sequences and Golomb’s three randomness postulates, the cross-correlation of <inline-formula> <tex-math notation="LaTeX">$m$ </tex-math></inline-formula>-sequences, the exp-Golomb code, the Golomb ruler, Costas arrays, Golomb invariants, polyominoes, the distribution of prime numbers, and irreducible polynomials.
A novel energy management scheme based on Best-response dynamics game in cognitive radio Ad hoc networks

Cognitive radio has been considered as promising techniques in wireless networks. However, most of previous works are focused on spectrum sharing and interference avoidance, and the energy management aspect is largely ignored. In this paper, we study power allocation in the environment of CR network without central processing unit: cognitive radio Ad hoc networks (CRAHNs). To improve the efficiency of management and the convergence speed of algorithm, we design the power sensing and adjusting scheme, and then propose iteration algorithm based on Best-response dynamics game. The maximum of total throughput is obtained by this scheme with the restriction of interference to primary users (PUs). Simulation results are presented to demonstrate the proposed scheme improved significantly in the performance with QoS demand.
SOTorrent: Reconstructing and Analyzing the Evolution of Stack Overflow Posts

Stack Overflow (SO) is the most popular question-and-answer website for software developers, providing a large amount of code snippets and free-form text on a wide variety of topics. Like other software artifacts, questions and answers on SO evolve over time, for example when bugs in code snippets are fixed, code is updated to work with a more recent library version, or text surrounding a code snippet is edited for clarity. To be able to analyze how content on SO evolves, we built SOTorrent, an open dataset based on the official SO data dump. SOTorrent provides access to the version history of SO content at the level of whole posts and individual text or code blocks. It connects SO posts to other platforms by aggregating URLs from text blocks and by collecting references from GitHub files to SO posts. In this paper, we describe how we built SOTorrent, and in particular how we evaluated 134 different string similarity metrics regarding their applicability for reconstructing the version history of text and code blocks. Based on a first analysis using the dataset, we present insights into the evolution of SO posts, e.g., that post edits are usually small, happen soon after the initial creation of the post, and that code is rarely changed without also updating the surrounding text. Further, our analysis revealed a close relationship between post edits and comments. Our vision is that researchers will use SOTorrent to investigate and understand the evolution of SO posts and their relation to other platforms such as GitHub.
Kinsenoside Ameliorates Oxidative Stress-Induced RPE Cell Apoptosis and Inhibits Angiogenesis via Erk/p38/NF-κB/VEGF Signaling

The pathological superoxidative condition that retinal pigment epithelium (RPE) cells experience contributed to the advancement of age-related macular degeneration (AMD), which was accompanied by significant neovascularization. Therefore, the discovery of novel pharmacological candidates to ameliorate oxidative damage (H2O2) against RPE cells and inhibit the following angiogenesis simultaneously is urgently needed. Herein, we found that kinsenoside (Kin), an active component derived from Anoectochilus roxburghii, was able to protect RPE cells effectively and attenuate subsequent angiogenesis. In this study, H2O2-induced oxidative injury reduced RPE cell viability and increased cell apoptosis, which was significantly rescued by the treatment with Kin. Compared with H2O2 alone, Kin decreased the levels of Bax and increased the production of Bcl-2 in RPE cells. H2O2-stimulated VEGF up-regulation was inhibited by Kin treatment. Human umbilical vein endothelial cell (HUVEC) neovascularization induced by conditioned medium (CM) from H2O2-stimulated RPE cells was attenuated by treatment with Kin, VEGF antagonist, NF-κB, Erk-MAPK, and p38-MAPK inhibitors. Additionally, H2O2-activated phosphorylated expression of IκBα, p65, Erk, and p38 in RPE cells was inhibited by treatment with Kin. Taken together, Kin protected RPE from apoptosis against oxidative stress while simultaneously decreasing apoptosis-related neovascularization. This could be ascribed to the inhibition of Erk/p38/NF-κB signaling by Kin that contributed to the resulting decreased VEGF expression in H2O2-treated RPE cells.
Security Analysis of Energy Internet With Robust Control Approaches and Defense Design

Power cyber-physical systems (PCPSs) are becoming increasingly complex and diverse, benefitting from all aspects of societal issues. A PCPS is a next-generation system that is a tight conjunction of computation, communication, control, and power systems. The integration of Internet of Things and PCPS generates a novel energy system, the Internet of Energy, which is the future of the energy system. In the same way, the connection of bulk components and the extensive communications among them has brought many insecurities, uncertainties, and security challenges. Thus, a study of the analysis and synthesis of the reliability and security of PCPS is presented in this paper. By considering the unsafe uncertainties, models are formulated for a general cyber-attack, and a double-loop architecture for security defense is designed. According to this framework, security control scenarios are obtained from the character of each kind of cyber-attack. Finally, a separately excited dc motor with uncertainty is used as an example to demonstrate the problem.
SOLID FUEL FROM EMPTY FRUIT BUNCH FIBER AND WASTEPAPERS PART 2: GAS EMISSION FROM COMBUSTION TEST

This research discussed on the results obtained for each sample that have been conducted to the solid fuel briquettes made of empty fruit bunch fiber and waste papers from view of gas emission content during combustion test. A good and quality briquette is the one that contained high oxygen and small amount of carbon monoxide, carbon dioxide, nitrogen and sulphur gases which released during the combustion. This is because, all these gases can cause air pollution and it is hazardous to human health. Low sulphur content is desirable in order to make this form renewable energy more environments friendly as compared to combustion of fossil fuels because combustion of agricultural wastes types will emit less sulphur oxide and react with water, oxygen and oxidants in forming the acidic compound that formed acid rain. Hence, the possibility result in this research is the development of solid fuel briquette by mixing the empty fruit bunch with a waste paper can be one sources of fuel energy. From the combustion analysis showed sample briquette of S/N 1 was found to be the best ratio as the amount that met the good environmental friendly aspects.
Characteristics of Amorphous Silicon Based Alloy Field Effect Transistors

We have developed a new theory to describe the current-voltage characteristics of amorphous silicon based alloy field effect transistors. We show that the transition from below to above threshold operation occurs when the Fermi level in the accumulation region moves from the deep to tail localized states in the energy gap and that the field effect mobility is dependent on gate voltage. We also propose a new technique to determine the flat-band voltage from the I-V characteristics in the below threshold regime.
Downregulation of ribonucleotide reductase subunits M2 induces apoptosis and G1 arrest of cervical cancer cells

Ribonucleotide reductase subunit M2 (RRM2) is associated with the biological behaviours of cancers, including apoptosis, cell proliferation, invasion, cell cycle and migration. Previous studies have suggested that the expression of RRM2 plays critical roles in tumorigenesis in several cancer types. However, the precise molecular mechanism remains unknown. We previously identified RRM2 as a novel downstream target that is activated by human papillomavirus E7, which activates the extracellular signal-regulated kinase 1/2 signalling pathway, but further studies are warranted to establish RRM2 as a therapeutic target. The results of the present study indicate that RRM2 is associated with cervical cancer cell apoptosis and proliferation. The downregulation of RRM2 significantly increased apoptosis, promoted cell cycle arrest at the G1 phase in vitro and inhibited tumour formation in nude mice transplant models in vivo. These results highlight the potential for inhibition of RRM2 expression as a promising therapeutic target for human cervical cancer treatment.
Effects of storage conditions on hatchability, embryonic survival and cytoarchitectural properties in broiler from young and old flocks

ABSTRACT Storing eggs at low temperature prior to incubation is common practice in the broiler hatchery industry; however, prolonged storage (beyond 7 d) is known to increase early embryonic mortality and reduce chick quality and performance. To better understand the basis of this mortality, we previously published milestone criteria to evaluate morphological and cellular properties of the freshly laid embryo. Using these criteria, in the present study we checked the effects of storage at 18°C and 12°C for up to 28 d on hatchability and chick quality. Furthermore, using a 3D high‐resolution episcopic microscopy (HREM) imaging system combined with standard and confocal microscopy and cell viability markers, we analyzed the effects of the different storage conditions on embryonic developmental stage, cytoarchitectural properties, mitotic index and cell survival. A total of 1,483 eggs from a young flock were divided in 2 groups, 18°C and 12°C, and stored for 7, 14, 21, and 28 d. Following storage, randomly selected 1,222 eggs were incubated, and the hatched chicks were evaluated for chick quality parameters. Nonhatched eggs were also analyzed to determine the stage of embryonic mortality. The remaining 261 eggs were isolated and analyzed for developmental stage, cytoarchitecture, mitotic index, and cell death following storage. Hatchability rates beyond 7 d of storage at 12°C were significantly improved compared to 18°C, and chick quality remained high. Similar results were obtained for an old flock's eggs (n = 1,350). Analyzing the embryos, at each time point, we found that at 12°C, the developmental progression during storage slows significantly, mitotic index—which at this temperature may indicate mitotic arrest—increases and the rate of early apoptosis is half than at 18°C. Moreover, the HREM system and histological sections showed that embryos stored at 18°C for prolonged times undergo dramatic cytoarchitectural changes that may be maladaptive to resuming normal development after diapause. We thus demonstrate the usefulness of the milestone criteria for predicting and studying the storage conditions that will allow for better performance in hatchery practice.
Understanding Monitoring Technologies for Adults With Pain: Systematic Literature Review

Background Monitoring of patients may decrease treatment costs and improve quality of care. Pain is the most common health problem that people seek help for in hospitals. Therefore, monitoring patients with pain may have significant impact in improving treatment. Several studies have studied factors affecting pain; however, no previous study has reviewed the contextual information that a monitoring system may capture to characterize a patient’s situation. Objective The objective of this study was to conduct a systematic review to (1) determine what types of technologies have been used to monitor adults with pain, and (2) construct a model of the context information that may be used to implement apps and devices aimed at monitoring adults with pain. Methods A literature search (2005-2015) was conducted in electronic databases pertaining to medical and computer science literature (PubMed, Science Direct, ACM Digital Library, and IEEE Xplore) using a defined search string. Article selection was done through a process of removing duplicates, analyzing title and abstract, and then reviewing the full text of the article. Results In the final analysis, 87 articles were included and 53 of them (61%) used technologies to collect contextual information. A total of 49 types of context information were found and a five-dimension (activity, identity, wellness, environment, physiological) model of context information to monitor adults with pain was proposed, expanding on a previous model. Most technological interfaces for pain monitoring were wearable, possibly because they can be used in more realistic contexts. Few studies focused on older adults, creating a relevant avenue of research on how to create devices for users that may have impaired cognitive skills or low digital literacy. Conclusions The design of monitoring devices and interfaces for adults with pain must deal with the challenge of selecting relevant contextual information to understand the user’s situation, and not overburdening or inconveniencing users with information requests. A model of contextual information may be used by researchers to choose possible contextual information that may be monitored during studies on adults with pain.
Role of Zinc Homeostasis in the Pathogenesis of Diabetes and Obesity

Zinc deficiency is a risk factor for obesity and diabetes. However, until recently, the underlying molecular mechanisms remained unclear. The breakthrough discovery that the common polymorphism in zinc transporter SLC30A8/ZnT8 may increase susceptibility to type 2 diabetes provided novel insights into the role of zinc in diabetes. Our group and others showed that altered ZnT8 function may be involved in the pathogenesis of type 2 diabetes, indicating that the precise control of zinc homeostasis is crucial for maintaining health and preventing various diseases, including lifestyle-associated diseases. Recently, the role of the zinc transporter ZIP13 in the regulation of beige adipocyte biogenesis was clarified, which indicated zinc homeostasis regulation as a possible therapeutic target for obesity and metabolic syndrome. Here we review advances in the role of zinc homeostasis in the pathophysiology of diabetes, and propose that inadequate zinc distribution may affect the onset of diabetes and metabolic diseases by regulating various critical biological events.
A General Audiovisual Temporal Processing Deficit in Adult Readers With Dyslexia.

Purpose Because reading is an audiovisual process, reading impairment may reflect an audiovisual processing deficit. The aim of the present study was to test the existence and scope of such a deficit in adult readers with dyslexia. Method We tested 39 typical readers and 51 adult readers with dyslexia on their sensitivity to the simultaneity of audiovisual speech and nonspeech stimuli, their time window of audiovisual integration for speech (using incongruent /aCa/ syllables), and their audiovisual perception of phonetic categories. Results Adult readers with dyslexia showed less sensitivity to audiovisual simultaneity than typical readers for both speech and nonspeech events. We found no differences between readers with dyslexia and typical readers in the temporal window of integration for audiovisual speech or in the audiovisual perception of phonetic categories. Conclusions The results suggest an audiovisual temporal deficit in dyslexia that is not specific to speech-related events. But the differences found for audiovisual temporal sensitivity did not translate into a deficit in audiovisual speech perception. Hence, there seems to be a hiatus between simultaneity judgment and perception, suggesting a multisensory system that uses different mechanisms across tasks. Alternatively, it is possible that the audiovisual deficit in dyslexia is only observable when explicit judgments about audiovisual simultaneity are required.
Trends in opioid and nonsteroidal anti-inflammatory use and adverse events.

OBJECTIVES To describe the prevalence and incidence of opioid and nonsteroidal anti-inflammatory drug (NSAID) use before and since the start of the Veterans Health Administration (VHA) Opioid Safety Initiative (OSI) and to assess rates of adverse events (AEs). STUDY DESIGN Historical cohort study. METHODS The OSI began in August 2012 and was fully implemented by the end of fiscal year (FY) 2013. The study timeframe was categorized into baseline (FY 2011-2012), transition (FY 2013), and postimplementation (FY 2014-2015) phases. Prevalence and incidence rates were calculated for opioid and NSAID users by quarter between FY 2011 and FY 2015. For AEs among new users of an NSAID or opioid, Cox proportional hazards models with inverse probability weighting were used to adjust for potential confounding. RESULTS There were 3,315,846 regular users of VHA care with at least 1 opioid and/or NSAID outpatient prescription between FYs 2011 and 2015. The quarterly opioid prevalence rate was approximately 21% during the baseline and transition phases, then decreased to 17.3% in the postimplementation phase. NSAID prevalence remained constant at about 16%. Opioid incidence rates gradually decreased (2.7% to 2.2%) during the study, whereas NSAID incidence rates remained about 2.2%. After inverse probability weighting, patients receiving opioids had a greater risk of cardiovascular events (hazard ratio [HR], 1.41; 95% CI, 1.36-1.47), acute kidney injury (HR, 2.60; 95% CI, 2.51-2.68), gastrointestinal bleeding (HR, 1.68; 95% CI, 1.56-1.81), and all-cause mortality (HR, 3.73; 95% CI, 3.60-3.87) than NSAID users. CONCLUSIONS Opioid use declined following implementation of the OSI, whereas NSAID use remained constant. Rates of AEs were higher among opioid users, which provides additional rationale for efforts to use NSAIDs for pain management when appropriate.
Association of FTO Polymorphisms with Obesity and Obesity-Related Outcomes in Portuguese Children

Background Several studies have reported an association between single nucleotide polymorphisms in the first intron of the FTO gene and body mass index (BMI) or obesity. However, this association has not yet been studied among the Portuguese population. This study aims to assess the association of three FTO polymorphisms (rs1861868, rs1421085 and rs9939609) with obesity-related outcomes in a sample of Portuguese children. Methods We examined a total of 730 children, 256 normal-weight (55.9% girls), 320 overweight (45.3% girls) and 154 obese (53.2% girls), aging from 6 to 12-years-old, recruited randomly from public schools in the central region of Portugal. DNA samples were genotyped for the three polymorphisms by allelic discrimination TaqMan assay. Association of the FTO polymorphisms with several anthropometric traits was investigated. Additionally, we tested association with the risk of obesity using overweight and obese vs. normal-weight children. Results We found significant associations of rs9939609 and rs1421085 polymorphisms with weight, BMI, BMI Z-score, waist circumference and hip circumference, even after age and gender adjustment (p<0.05 in all traits). For rs1861868 polymorphism, marginally significant associations were obtained with weight (p = 0.081) and BMI (p = 0.096) after adjustment for age and gender. In case-control studies, both rs9939609 and rs1421085 polymorphisms were significantly associated with obesity (OR 1.97; 95% CI, 1.08–3.59; p = 0.026; OR 2.11; 95% CI, 1.17–3.81; p = 0.013, respectively) but not with overweight (p>0.05). Haplotype analyses identified two combinations (ACA and GCA) associated with a higher risk of obesity (OR 1.53; 95% CI, 1.06–2.22; p = 0.023; OR 1.73; 95% CI, 1.06–2.87; p = 0.030, respectively). Conclusions This study provides the first evidence for the association of FTO polymorphisms with anthropometric traits and risk of obesity in Portuguese children.