Miracle-dz/UniFAR-FTUs huggingface dataset:
On making xen detect hypercalls and memory accesses for simulating virtualization-enabled processors

Due to the widespread use of cloud-based systems that are shared by multiple users, new processors are enhanced for security in virtualization. However, it is a challenging task to develop simulators for such processors, mainly, due to the lack of relevant information at the application level for computing performance parameters. This paper proposes a methodology to extract the required information from the hypervisor and transfer it to the hardware-based simulator for simulation of such processors. The paper proposes an approach to detect hypercalls made by the guest operating system during the execution of the guest application program on Xen hypervisor. This paper considers five hypercalls, viz., mmu_update, memory_op, update_va_mapping, grant_table_op and mmuext_op. The results show that for the guest application executed, among these five hypercalls, mmu_update is called the maximum number of times, while memory_op is called the minimum number of times. The paper also proposes an approach to signal the memory accesses by Xen on the communications (COM) port. This signal is observed on the cathode ray oscilloscope (CRO) and may be utilized for simulation. This research is valuable as it concludes that virtualization-enabled processors may be effectively simulated by extracting the required information from the hypervisor.
Sponsored content and user engagement dynamics on Instagram

In this work, we analyze sponsored content and its impact on user engagement in the context of influencer marketing on Instagram. We collected and characterized a large-scale dataset of Instagram profiles and proposed metrics to capture the impact that advertisement posting strategies have on audience engagement over time. In particular, we analyze how the variation in the number of sponsored posts correlates with the number of likes and comments on a weekly basis. We show that an increasing amount of sponsored content can negatively affect audience engagement with an influencer's profile. Nevertheless, our analysis also suggests that there is a variety of ways to mitigate this negative effect, such as strategic usage of mentions and hashtags, the textual content of a sponsored post, as well as seasonal information.
Identifying Social Network Delusion to Investigate Addiction Ratio using Data Mining

Mining social media is the process of defining, analyzing, and extracting applicative patterns and trends from row social media data. Social media are very popular way of expressing opinions and interacting with many individual in the online world. However growing number of social network delusion among various age categories are recently noted. Mental sickness can have a deep influence on person, families, and society as well. Hence, we propose a framework that analyzes Social Network Delusion (SND) and investigates the addiction ratio. This work first defines the framework for analyzing the social network delusion based on mining online social behavior that provides an early stage opportunity to identify SNDs (Social Network Delusion). The proposed system mainly works in three phases. Feature extraction and analysis of the various posts posted by the users on Facebook, Instagram and Twitter is performed by using mining algorithm in the first step. The SND prediction using the extracted features is done in the second phase; Third phase uses the predicted results as an input for investigating the addiction ratio. We investigate the addiction ratio among different genders and age groups for analyzing the prevention strategies against growing number of SND.
XIEv: dynamic analysis for crawling and modeling of web applications

Researchers and practitioners in the fields of testing, security assessment and web development seeking to evaluate a given web application often have to rely on the existence of a model of the respective system, which is then used as input to task-specific tools. Such models may include information on HTTP endpoints and their parameters, available user actions/event listeners and required assets. Unfortunately, this data is often unavailable in practice, as only rigorous development practices or manual analysis guarantee their existence and correctness. Crawlers based on static analysis have traditionally been used to extract required information from existing sites. Regrettably, these tools can not accurately account for the dynamic behavior introduced by JavaScript and other technologies that are prevalent on modern sites. While methods based on dynamic analysis exist, they are not fully capable of identifying event listeners and their effects. This work presents XIEv, an approach for dynamic analysis of web applications that produces an execution trace usable for the extraction of navigation graphs, identification of bugs at runtime and enumeration of resources requested by each page. It offers improved recognition and selection of event listeners as well as a greater range of observed effects compared to existing approaches.
Growth Factors Enhance Interleukin-1 –Induced Persistent Activation of Nuclear Factor- B in Rat Vascular Smooth Muscle Cells

Objective—Activation of extracellular signal–regulated kinases (ERKs) is required for interleukin-1 to persistently activate nuclear factor (NF)B and concomitantly express inducible NO synthase (iNOS) in rat vascular smooth muscle cells (VSMCs). The present study examined whether platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) could influence the VSMC response to interleukin-1 via an ERK-related signaling pathway. Methods and Results—Treatment of VSMCs with PDGF or EGF alone potently induced ERK phosphorylation and DNA synthesis but did not induce NFB activation or iNOS expression. However, either PDGF or EGF markedly enhanced interleukin-1 –induced persistent NFB activation and iNOS expression but did not affect the early and transient NFB activation. Growth factor–induced DNA synthesis was attenuated in the presence of interleukin-1 . Inhibition of ERK phosphorylation with selective inhibitors (PD98059 or U0126) attenuated interleukin-1 –induced persistent NFB activation and iNOS expression in either the absence or presence of the growth factors. Conclusions—These results indicate that interleukin-1 –induced expression of NFB–dependent genes, such as iNOS, is potentiated in the presence of growth factors through a mechanism requiring ERK-dependent enhanced NFB activation, and the results also suggest that NFB activation is not required for PDGF or EGF to trigger DNA synthesis in VSMCs. (Arterioscler Thromb Vasc Biol. 2002;22:1811-1816.)
Somatostatin-Expressing Interneurons in the Auditory Cortex Mediate Sustained Suppression by Spectral Surround

Sensory systems integrate multiple stimulus features to generate coherent percepts. Spectral surround suppression, the phenomenon by which sound-evoked responses of auditory neurons are suppressed by stimuli outside their receptive field, is an example of this integration taking place in the auditory system. While this form of global integration is commonly observed in auditory cortical neurons, and potentially used by the nervous system to separate signals from noise, the mechanisms that underlie this suppression of activity are not well understood. We evaluated the contributions to spectral surround suppression of the two most common inhibitory cell types in the cortex, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, in mice of both sexes. We found that inactivating SOM+ cells, but not PV+ cells, significantly reduces sustained spectral surround suppression in excitatory cells, indicating a dominant causal role for SOM+ cells in the integration of information across multiple frequencies. The similarity of these results to those from other sensory cortices provides evidence of common mechanisms across the cerebral cortex for generating global percepts from separate features. SIGNIFICANCE STATEMENT To generate coherent percepts, sensory systems integrate simultaneously occurring features of a stimulus, yet the mechanisms by which this integration occurs are not fully understood. Our results show that neurochemically distinct neuronal subtypes in the primary auditory cortex have different contributions to the integration of different frequency components of an acoustic stimulus. Together with findings from other sensory cortices, our results provide evidence of a common mechanism for cortical computations used for global integration of stimulus features.
Management of hepatitis C infection in the era of direct-acting antiviral therapy

Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.
Dicer up-regulation by inhibition of specific proteolysis in differentiating monocytic cells

Significance Dicer is a ribonuclease III enzyme in biosynthesis of miRNAs, regulators of gene expression involved in macrophage differentiation. We found a specific truncation of Dicer in monocytic cells resulting from apparently constitutive cleavage by a serine protease. Inhibition of this proteolytic truncation, which occurred during macrophage differentiation in presence of TLR ligands or prostaglandin E2, up-regulates full-length Dicer and promotes miR biosynthesis. Regulation of transcription of pri-miRNA is one mode to regulate biosynthesis of mature miRNA. Inhibition of constitutive proteolysis of Dicer, as described here, provides a second layer of regulation, at the level of miRNA processing. Our data provide insights to Dicer and miRNAs in macrophage polarization/differentiation, a key process in the innate immune response. Dicer is a ribonuclease III enzyme in biosynthesis of micro-RNAs (miRNAs). Here we describe a regulation of Dicer expression in monocytic cells, based on proteolysis. In undifferentiated Mono Mac 6 (MM6) cells, full-length Dicer was undetectable; only an ∼50-kDa fragment appeared in Western blots. However, when MM6 cells were treated with zymosan or LPS during differentiation with TGF-β and 1,25diOHvitD3, full-length Dicer became abundant together with varying amounts of ∼170- and ∼50-kDa Dicer fragments. Mass spectrometry identified the Dicer fragments and showed cleavage about 450 residues upstream from the C terminus. Also, PGE2 (prostaglandin E2) added to differentiating MM6 cells up-regulated full-length Dicer, through EP2/EP4 and cAMP. The TLR stimuli strongly induced miR-146a-5p, while PGE2 increased miR-99a-5p and miR-125a-5p, both implicated in down-regulation of TNFα. The Ser protease inhibitor AEBSF (4-[2-aminoethyl] benzene sulfonyl fluoride) up-regulated full-length Dicer, both in MM6 cells and in primary human blood monocytes, indicating a specific proteolytic degradation. However, AEBSF alone did not lead to a general increase in miR expression, indicating that additional mechanisms are required to increase miRNA biosynthesis. Finally, differentiation of monocytes to macrophages with M-CSF or GM-CSF strongly up-regulated full-length Dicer. Our results suggest that differentiation regimens, both in the MM6 cell line and of peripheral blood monocytes, inhibit an apparently constitutive Dicer proteolysis, allowing for increased formation of miRNAs.
Novel PPP1CB‐ALK fusion in spindle cell tumor defined by S100 and CD34 coexpression and distinctive stromal and perivascular hyalinization

A novel group of S100‐ and CD34‐positive spindle cell tumors with distinctive stromal and perivascular hyalinization harboring recurrent gene fusions involving kinases including RAF1, BRAF, NTRK1/2/3, and RET have been recently reported. To our knowledge, no such cases harboring ALK rearrangements have been identified. We report a previously healthy 41‐year‐old male with a 12‐cm intramuscular shoulder mass. The tumor was composed of bland‐appearing spindled to epithelioid cells, arranged in a patternless pattern in a background of loose myxoid stroma containing striking amianthoid‐like stromal collagen and perivascular rings. In accordance with the previously reported tumors, the tumor cells showed diffuse immunopositivity with S100 and CD34, while lacking SOX10 expression. Targeted RNA‐based next‐generation sequencing identified a novel serine/threonine‐protein phosphatase PP1‐beta‐catalytic subunit (PPP1CB)‐ALK fusion gene. Although ALK break‐apart was not detected by FISH, likely due to a paracentric inversion of chromosome 2, the presence of the fusion was confirmed by Sanger sequencing showing a 10‐bp linker between exon 6 of PPP1CB and intron 19 of ALK while maintaining reading frame. Subsequent ALK‐1 immunostain exhibited diffuse cytoplasmic staining in the tumor cells. Our case expands the molecular genetic spectrum of the distinctive group of spindle cell tumors with CD34/S100+ immunophenotype, supporting the important role of various kinases as drivers of oncogenesis. Awareness of this entity including its unique morphologic and immunophenotypic features as well as its interchangeable kinase gene fusions is crucial for correct classification and potential targeted therapy, particularly in aggressive subsets.
Link N as a therapeutic agent for discogenic pain

Neurotrophins (NTs) are the major contributors of sensory axonal sprouting, neural survival, regulation of nociceptive sensory neurons, inflammatory hyperalgesia, and neuropathic pain. Intervertebral disc (IVD) cells constitutively express NTs. Their expression is upregulated by proinflammatory cytokines present in the IVD during degeneration, which can promote peripheral nerve ingrowth and hyperinnervation, leading to discogenic pain. Currently, there are no targeted therapies that decrease hyperinnervation in degenerative disc disease. Link N is a naturally occurring peptide with a high regenerative potential in the IVD. Therefore, the suitability of Link N as a therapeutic peptide for suppressing NTs, which are known modulators and mediators of pain, was investigated. The aim of the present study is to determine the effect of Link N on NTs expression, nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), and their cognate receptors TrkA and TrkB as they are directly correlated with symptomatic back pain. Furthermore, the neurotransmitter (substance P) was also evaluated in human annulus fibrosus (AF) cells stimulated with cytokines. Human AF cells isolated from normal IVDs were stimulated with interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) in the presence or absence of Link N. NGF release in the media was evaluated by Western blotting. Total RNA was isolated and gene expression was measured using real‐time PCR. Gene expression of NGF, BDNF, TrkA, and TrkB significantly decreased in human disc cells stimulated with either IL‐1β or TNF‐α supplemented with Link N when compared to the cells stimulated only with IL‐1β or TNF‐α. NGF protein expression was also suppressed in AF cells coincubated with Link N and IL‐1β when compared to the cells stimulated only with IL‐1β. Link N can suppress the stimulation of NGF, BDNF, and their receptors TrkA and TrkB in AF cells in an inflammatory milieu. Thus, coupled with previous observations, this suggests that administration of Link N has the potential to not only repair the discs in early stages of the disease but also suppress pain.
Development and Validation of the Data Instrument for Surgical Global Outreach

Supplemental Digital Content is available in the text. Summary: Countless efforts have been made by global surgery outreach organizations to provide care to individuals in low- and middle-income countries; however, there is a paucity of data on these interventions. The authors created the Data Instrument for Surgical Global Outreach to collect basic program, cost, and clinical data on surgical outreach efforts using the literature and the experience of our team. The authors performed a two-round modified Delphi technique to build content validity on the instrument and establish consensus. Experts engaged in global health or global surgery as a health care provider, researcher, or policymaker participated in the validation. In addition, the authors calculated Cronbach’s alpha to determine the degree of agreement among experts. A total of 22 experts in global health participated in the validation of the data tool. Changes were made to reword, combine, remove, add, clarify, and simplify data points. There was a unanimous decision to accept the revised data collection instrument among the experts after the second Delphi round. Cronbach’s alpha was 0.86 for the first round and 0.95 for the second round, indicating a high degree of internal consistency. The global surgery outreach community must define a set of strategies to collect more robust data on surgical outreach efforts to low- and middle-income countries. Such data will permit policymakers to identify shortfalls in programs and researchers to pursue sustainable treatment modalities and processes of care. Quality collaboratives for surgical outreach organizations may serve as a tool to overcome variation, reduce cost, and improve the quality of care for patients.
Aos que clamam pelas evidências científicas em homeopatia

Homeopathy is a medical approach with 200 years of history; along this time it demonstrated its ability to solve problems, with low cost, broad scope and unquestionable social acceptance. According to estimates, approximately 500 million people use homeopathy worldwide, corresponding to about 7% of the world population. However, there are still hindrances to its integration to conventional medicine that need to put into perspective and removed. The aim of the present article is to contextualize homeopathy as a science and an art in Brazil and worldwide. We analyzed some relevant aspects, such as profile of users, their reasons to choose homeopathy and historical and social contexts for the inclusion of homeopathy in healthcare and educational systems. We conclude that homeopathy is an ethical medical system that provides systemic and safe treatment to patients, with optimal costbenefit ratio. Homeopathy should be included in universities, schools of medicine and
Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb

Abstract Harmful environmental agents cause nasal inflammation, and chronic nasal inflammation induces a loss of olfactory sensory neurons (OSNs) and reversible atrophy of the olfactory bulb (OB). Here, we investigated the mechanisms underlying this inflammation-induced OB atrophy by histologically and biochemically comparing the OB changes in mouse models of nasal inflammation and odor deprivation. In addition, we examined whether odor stimulation is necessary for OB recovery from atrophy. One group of adult male C57BL/6 mice was administered lipopolysaccharide (LPS) unilaterally for 10 weeks to induce nasal inflammation (control animals received saline), and a second group received unilateral naris closures (NCs) for 10 weeks of odor deprivation. The OBs atrophied in both models, but odor deprivation shrank the glomerular, external plexiform, mitral, and granule cell layers (GCLs), whereas the olfactory nerve, glomerular, and external plexiform layers (EPLs) atrophied as a result of nasal inflammation. Additionally, nasal inflammation, but not odor deprivation, caused neuroinflammation in the OB, inducing glial activation and elevated expression of interleukin-1β (IL-1β) and TNFα. After 10 weeks of nasal inflammation, mice were housed for another 10 weeks with no additional treatment or with unilateral NC. Nasal inflammation and glial activation subsided in both groups, but glomerular and EPLs recovered only in those with no additional treatment. Our findings demonstrate that nasal inflammation and odor deprivation differentially induce layer-specific degeneration in the OB, that loss of OSN activity rather than neuroinflammation is a major cause of inflammation-induced OB atrophy, and that odor stimulation is required for OB recovery from atrophy.
Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes

OBJECTIVE To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone. RESEARCH DESIGN AND METHODS Forty-five patients with poorly controlled (HbA1c 7–11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA), 2) canagliflozin 100 mg/day (CANA), or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated. RESULTS The mean decrease from baseline to 16 weeks in HbA1c was −1.67 ± 0.29% (P = 0.0001), −0.89 ± 0.24% (P = 0.002), and −1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was −6.0 ± 0.8 kg (P < 0.0001), −3.5 ± 0.5 kg (P < 0.0001), and −1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked. CONCLUSIONS These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.