Miracle-dz/UniFAR-FTUs huggingface dataset:
On neutrophil extracellular traps in leukocyte-dependent inflammation

Leukocyte recruitment to a site of an infection is a hallmarks of body’s host response. However, inappropriate accumulation of leukocytes can cause tissue damage and organ failure. The mechanisms of leukocyte accumulation may vary depending on different stimuli and organs. Herein, we visualized the process and explored the underlying mechanisms of leukocyte recruitment in response to different stimuli or conditions by intravital microscopy. We examined the role of polyphosphates (PolyPs), neutrophil extracellular trap (NET)-associated proteins and endothelial Midline 1 (Mid1) in regulating leukocyte recruitment during inflammation. We observed that neutrophils constitute the main recruited cells in response to PolyP-induced inflammation, and that interactions between P-selecin and P-selectin glycoprotein ligand-1 (PSGL1) play a dominant role in leukocyte rolling in microvessels. Moreover, both Mac-1 and LFA-1 contributed to leukocyte firm adhesion. In NET-induced inflammation, NET-associated microparticles (MPs) and S100A9 were found to play significant a role in regulating leukocyte accumulation. It was observed that NET-MP complexes trigger leukocyte recruitment via high mobility group box 1 (HMGB1) and toll-like receptor TLR2 and TLR4. S100A9 not only regulates NET-mediated leukocyte recruitment, but also regulates NET formation via reactive oxygen species (ROS) formation. Since leukocyte recruitment is the result of interactions between leukocytes and endothelial cells, we also evaluated a potential target on endothelial cells in septic lung. It was found that Mid1 is overexpressed in septic lung postcapillary venules and in TNF-α-stimulated endothelial cells in vitro. Silencing of Mid1 reduced ICAM-1 expression and leukocyte adhesion to the endothelial cells both in vitro and in vivo. In addition, we also found that protein phosphatase 2Ac (PP2Ac) is the target of Mid1 protein, indicating that the Mid1-PP2Ac axis regulate leukocyte accumulation via ICAM-1 expression. Taken together, these findings give us further understanding of leukocyte accumulation during inflammation and suggest that targeting these proteins would be an effective ways to ameliorate excessive leukocyte accumulation and tissue damage during local or systemic inflammation.
Validating Scliar’s early literacy system: The grapheme-phoneme relation Validação do Sistema Scliar de alfabetização: a relação grafema-fonema

The main purpose is discussing Scliar’s Early Literacy Development System (SSA) first validity evidence. Method: Sixteen subjects (10 girls and 6 boys) comprised the Experimental Group, EG (mean age 6.02) and 16 subjects (7 girls and 9 boys) formed the Control Group, CG (mean age 6.10). At the experiment beginning, the EG was submitted to an intervention program based on SSA. Two master degree students developed the experiment, guided by Scliar-Cabral, during 2011. They visited the EG’s school twice each week. After this intervention, both groups read aloud a list of 38 pseudo-words with four or five graphemes, one of the tasks composing the Battery of Reception and Production of Verbal Language (Scliar-Cabral, 2003b, 119-250). Each pseudo-word was signaled by the experimenter. The task was designed to assess children’s ability to convert a grapheme into its correspondent phoneme. Results: Using the confidence level of 5% (α = 0.05), with freedom (df) degree 30, we obtained a pvalue of 0.01 as a result of a t test (independent samples, two-tailed test, equal variances). This value is below the limit for the null hypothesis acceptance, that is p > α = 5%. Thus, there is no more than 1% chance that the differences between the data averages from the two classes are randomly determined. The effect size was large, with a Cohen’s d value of 0.97. Test results indicate that SSA application influenced the experimental group performance.
How to Put Through Change in Collective Binary Decisions

We consider the following decision scenario: a society of voters has to find an agreement on a set of proposals, and every single proposal is to be accepted or rejected. Each voter supports a certain subset of the proposals–the favorite ballot of this voter–and opposes the remaining ones. He accepts a ballot if he supports more than half of the proposals in this ballot. The task is to decide whether there exists a ballot approving a set of selected proposals (agenda) such that all voters (or a strict majority of them) accept this ballot. On the negative side both problems are NP-complete, and on the positive side they are fixed-parameter tractable with respect to the total number of proposals or with respect to the total number of voters. We look into further natural parameters and study their influence on the computational complexity of both problems, thereby providing both tractability and intractability results. Furthermore, we provide tight combinatorial bounds on the worst-case size of an accepted ballot in terms of the num-
Carbapenemase typing and resistance profile of enteric bacteria isolate with reduced sensitivity to carbapenems in a Lebanese tertiary care center

Objective: Nowadays-resistant bacteria represent worldwide a public health problem Leading in some cases to a stalemate without any possible treatment. Therefore, early detection and identification of carbapenemase-producing gram-negative bacteria (GNB) is of crucial importance. Consequently, we conducted a study in a tertiary care hospital to analyze the resistance phenotype of the carbapenem-resistant GNB (CRGNB). Methods: This study investigated all the CRGNB from September 2014 till January 2016. A total of 40/126 isolates were randomly collected and tested by susceptibility test in addition to a real time multiplex PCR to detect the carbapenemase-coding genes (bla SPC, bla IMP1, bla VIM, bla NDM, bla KPC, et bla OXA-48). The examined isolates were: Escherichia coli (70%), Klebsiellapneumoniae (20%), Enterobacteraerogenes (2,5%), Enterobacter cloacae (2.5%) and Klebsiellaoxytoca (2.5%). Results: All (100%) of the examined isolates were intermediate or resistant to ertapenem, 85% intermediate or resistant to imipenem and/or meropenem. Additionally, 33/40 of the isolates (82.5%) were bla OXA-48 positive, and one isolate (2.5%) is bla NDM positive. E. coli was the bacteria that expressed the most OXA-48 (26/40) (65%). Out of the 40 isolates in our study, 6 did not express carbapenemases although they have shown resistance to carbapenems. Conclusion: This study reports the emergence of CPGNB in our medical center especially bla OXA-48 with a high resistance pattern leading to narrow therapeutic options. This study indicts the importance of Carbapenemase typing and resistance profile of enteric bacteria isolate with reduced sensitivity to carbapenems in a Lebanese tertiary care center Alexandre Malek1,2, Josselin Abi Chebel2, Hadi Younes1,2, Jacques Choucair1,2, Nadim Azar3 1 Infectious Diseases Department, Hôtel Dieu de France hospital. 2 Saint Joseph University, School of Medicine, Beirut. 3 Head of Microbiology laboratory, Hôtel Dieu de France hospital, Saint Joseph. University, School of Medicine, Beirut. Contact information:
Agent-based Simulation of Information and Communications Technology Practicum Courses for Engineering Students at Instituto Tecnológico Metropolitano

—In this paper, a simulation of enlisting and use of free practicum courses for engineering students from Instituto Tecnológico Metropolitano (ITM) is presented. Currently, this university is interested in getting better results to rank more competitively among other universities. Although the current courses are free, a high quality offer is evidently more expensive and we need to maximize the impact of the students in the labor market. In Colombia, many universities certify engineering students in computer sciences so, in order to attend the current needs of our institution and the labor market, we would like to contribute to decision-making processes through agent-based simulation regarding what Information Communications Technologies courses may fit best for the community and the industrial clusters ITM students are and will be working in.
Efficacy and Safety of Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Enterobacterales Bloodstream Infection: a Systematic Review and Meta-Analysis

Ceftazidime-avibactam (CAZ-AVI) has been used as a frontline agent in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, the efficacy and safety of CAZ-AVI on carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) remain unclear. ABSTRACT Several clinicians use ceftazidime-avibactam (CAZ-AVI) to treat bloodstream infections (BSIs) due to carbapenem-resistant Enterobacterales (CRE), although no conclusive data support this practice. We aimed to assess the efficacy and safety of CAZ-AVI in the treatment of CRE bacteremia. PubMed, Embase, and Cochrane Library were systematically searched until 5 November 2021. Studies comparing the clinical outcome of CAZ-AVI with other regimens in CRE BSI were included if they reported data on mortality. Results were expressed as risk ratios (RRs) or mean differences with accompanying 95% confidence intervals (95% CIs). Eleven articles with 1,205 patients were included. CAZ-AVI groups showed a significantly lower 30-day mortality than control groups of other regimens (RR = 0.55, 95% CI of 0.45 to 0.68, P < 0.00001). The result is robust when a colistin-based regimen serves as the control group (RR = 0.48, 95% CI 0.33 of 0.69, P < 0.0001). In subgroup meta-analyses, the 30-day mortality was significantly lower in patients infected with CRE producing Klebsiella pneumoniae carbapenemase (RR = 0.59, 95% CI of 0.46 to 0.75, P < 0.0001). Additionally, patients in CAZ-AVI groups had a significantly higher clinical cure rate (RR = 1.75, 95% CI of 1.57 to 2.18, P < 0.00001) and lower nephrotoxicity rate (RR = 0.41, 95% CI of 0.20 to 0.84, P = 0.02). No significant differences of relapse rates were demonstrated in 2 groups (RR = 0.69, 95% CI of 0.29 to 1.66, P = 0.41). Although the current study is based on observational studies with a small sample of participants, the findings suggest that CAZ-AVI treatment is effective and safe compared with other antibiotics, including colistin, in CRE BSI. IMPORTANCE Ceftazidime-avibactam (CAZ-AVI) has been used as a frontline agent in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, the efficacy and safety of CAZ-AVI on carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) remain unclear. Patients with CRE BSIs were often enrolled in small-sized clinical studies, together with other sites of infections, which reported pooled results. In this meta-analysis, the efficacy and safety were compared between CAZ-AVI and any other regimens used against CRE infections. The findings suggest that patients in the CAZ-AVI group had a significantly lower 30-day mortality than any other regimens and than colistin-based regimens. This paper provides a rationale for the use of CAZ-AVI in one of the most urgent antimicrobial-resistant infections of CRE bloodstream infections.
The incidence of lumbar spine surgery following Minimally Invasive Lumbar Decompression and Superion Indirect Decompression System for treatment of lumbar spinal stenosis: a retrospective review

Lumbar spinal stenosis affects more than 200,000 adults in the United States, resulting in approximately 38,000 operations among the Medicare population and greater than $1.5 billion in hospital bills alone. Fortunately, Minimally Invasive Lumbar Decompression (MILD) and the Superion Indirect Decompression System have shown lasting benefit and cost savings compared to more aggressive surgical options.
Characterizing and Quantifying Extrahepatic Metabolism of (−)-Δ9-Tetrahydrocannabinol (THC) and Its Psychoactive Metabolite, (±)-11-Hydroxy-Δ9-THC (11-OH-THC)

(−)-Δ9-Tetrahydrocannabinol (THC) is the psychoactive constituent of cannabis, a drug recreationally consumed orally or by inhalation. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict systemic and tissue exposure to THC and its psychoactive metabolite, (±)-11-hydroxy-Δ9-THC (11-OH-THC). To populate a THC/11-OH-THC PBPK model, we previously characterized the depletion clearance of THC (by CYP2C9) and 11-OH-THC (by UDP-glucuronosyltransferase (UGT), CYP3A, and CYP2C9) in adult human liver microsomes. Here we focused on quantifying extrahepatic depletion clearance of THC/11-OH-THC, important after oral (intestine) and inhalational (lung) consumption of THC as well as prenatal THC use (placenta and fetal liver). THC (500 nM) was metabolized in adult human intestinal microsomes (n = 3–5) by CYP2C9 [Vmax: 1.1 ± 0.38 nmol/min/mg; Michaelis-Menten constant (Km): 70 nM; intrinsic clearance (CLint): 15 ± 5.4 ml/min/mg; fraction metabolized (fm): 0.89 ± 0.31 at concentration ≪ 70 nM] and CYP3A (CLint: 2.0 ± 0.86 ml/min/mg; fm: 0.11 ± 0.050). 11-OH-THC (50 nM) was metabolized by CYP3A (CLint: 0.26 ± 0.058 ml/min/mg; fm: 0.51 ± 0.11) and UGT2B7 (CLint: 0.13 ± 0.027 ml/min/mg; fm: 0.25 ± 0.053). THC at 500 nM (CLint: 4.7 ± 0.22 ml/min/mg) and 11-OH-THC at 50 nM (CLint: 2.4 ± 0.13 ml/min/mg) were predominately (fm: 0.99 and 0.80, respectively) metabolized by CYP3A in human fetal liver microsomes (n = 3). However, we did not observe significant depletion of THC/11-OH-THC in adult lung, first trimester, second trimester, or term placentae microsomes. Using PBPK modeling and simulation, these data could be used in the future to predict systemic and tissue THC/11-OH-THC exposure in healthy and special populations. SIGNIFICANCE STATEMENT This is the first characterization and quantification of (−)-Δ9-tetrahydrocannabinol (THC) and (±)-11-hydroxy-Δ9-THC (11-OH-THC) depletion clearance by cytochrome P450 and UDP-glucuronosyltransferase enzymes in extrahepatic human tissues: intestine, fetal liver, lung, and placenta. These data can be used to predict, through physiologically based pharmacokinetic modeling and simulation, systemic and tissue THC/11-OH-THC exposure after inhalational and oral THC use in both healthy and special populations (e.g., pregnant women).
Exploring nose to brain nano delivery for effective management of migraine.

Migraine is a disabling disease, characterized by severe throbbing headache. Patients demand quick relief from this pain. The presence of blood brain barrier does not permit the drug to penetrate the brain effectively. Administration of conventional anti-migraine medications via oral route leads to erratic absorption of drugs. Delayed gastric emptying is also responsible for ineffective absorption of drug. Migraine induced nausea and vomiting, further limits patient compliance to oral medication. Other limitations associated with oral route include extensive first pass metabolism, slow onset of action, inability to cross blood brain barrier and requirement of large amount of dose/dosage and frequent administration. The anti-migraine drugs used in migraine like triptans are therapeutically effective but have low bioavaialability on oral administration. Also, these drugs are associated with several cardiovascular complications. The oral dose of most antimigraine drugs oral tritpans, Ergot amine, NSAIDs and CGRP antagonist is quite high because of their poor bioavailability. As a result of these drugs are associated with several side effects. This aspects necessitates the need of developing a dosage form that can deliver drug directly brain thereby reducing the dose. Use of invasive techniques to deliver these therapeutics to the brain do exist, however, they are painful, require expert assistance and are not cost-effective approach for migraine treatment. These limitations demand development of a novel non-invasive approach that is safe, efficacious and has high patient compliance. As, reported it is possible to target the brain tissue by administering the drug intranasally using olfactory and the trigeminal pathway. This route is non-invasive, avoids first-pass metabolism, eliminates nausea and vomiting, helps reduce dose, and thus helps achieve increase patient compliance. Some factors like solubility, lipophilicity of the drug, mucociliary clearance, enzymatic degradation hinder the bioavailability of the drug by nasal route. Therefore, there is a grave need to develop novel nasal formulations with prolonged nasal residence time, which can modulate pharmacokinetics for adequate therapeutic response, and render efficient yet robust brain targeting. It is necessary to consider these challenges in developing efficient intranasal dosage form. This review gives a brief overview of all the novel carriers reported for improving the treatment of migraine. Nanocarrier based delivery systems like in-situ gels, micro emulsion, nanoemulsion, nanoparticles, vesicular systems, micelles, and microspheres used in nose to brain delivery of migraine therapeutics are also discussed in the article.
Naturally occurring prenylated stilbenoids: food sources, biosynthesis, applications and health benefits

Abstract Prenylated stilbenoids are a unique class of natural phenolic compounds consisting of C6-C2-C6 skeleton with prenyl substitution. They are potential nutraceuticals and dietary supplements presented in some edible plants. Prenylated stilbenoids demonstrate promising health benefits, including antioxidant, anti-cancer, anti-inflammatory, anti-microbial activities. This review reports the structure, bioactivity and potential application of prenylated stilbeniods in food industry. Edible sources of these compounds are compiled and summarized. Structure-activity relationship of prenylated stilbenoids are also highlighted. The biosynthesis strategies of prenylated stilbenoids are reviewed. The findings of these compounds as food preservative, nutraceuticals and food additive are discussed. This paper combines the up-to-date information and gives a full image of prenylated stilbenoids.
Non-linguistic auditory speech processing

Abstract Objectives A method for testing auditory processing of non-linguistic speech-like stimuli was developed and evaluated. Design Monosyllabic words were temporally reversed and distorted. Stimuli were matched for spectrum and level. Listeners discriminated between distorted and undistorted stimuli. Study sample Three groups were tested. The Normal group was comprised of 12 normal-hearing participants. The Senior group was comprised of 12 seniors. The Hearing Loss group was comprised of 12 participants with thresholds of at least 35 dB HL at one or more frequencies. Results The Senior group scored lower than the Normal group, and the Hearing Loss group scored lower than the Senior group. Scores for forward compressed speech were slightly higher than backward compressed speech but the difference was not statistically significant. Retest scores were slightly higher than scores on the first test, but the difference was not statistically significant. Conclusions Large differences in discrimination of distorted speech were observed among the three groups. Age and hearing loss separately affected performance. The depressed performance of the Senior group may be a result of “hidden hearing loss” that is attributed to cochlear synaptopathy. The backward-distorted speech task may be a useful non-linguistic test of speech processing that is language independent.
Comparing the Prevalence of Alcohol, Combustible and Electronic Cigarettes, Hookah, and Marijuana, in Music Videos across 6 Genres of Popular Music from 2014–2020

Abstract Objectives To determine the frequency of alcohol, marijuana, cigarettes/cigars, e-cigarettes, and hookah portrayals in popular music lyrics and videos on YouTube across 6 genres over 7 years; assess percent change over the years, document brand placement, and determine frequency of promotion of substances/devices by Teen Choice Award celebrities. Methods We analyzed 699 songs from the Billboard Hot 100 between 2014 and 2020. Two raters coded 10% of the songs to establish inter-rater reliability and remaining songs were reviewed by one rater. Results The majority of songs (59.2%) on YouTube included either lyrical or video depictions and 20.6% included both. Songs that featured substances/devices were viewed 148 billion times on YouTube as of February 2021. Nearly 25% of videos depicting substances/devices featured branding. Forty-three (18.22%) of the music celebrities who featured substances/devices in their videos received one or more Teen Choice Awards during the study period. Conclusions Popular music celebrities promote substance use in their lyrics and music videos, which are easily accessible to children and adolescents. Some of these celebrities are highly popular and influential among adolescents. Policy Implications. Findings support the need to limit promotion of these substances to youth by influencers to reduce substance use and misuse.
The Effectiveness of Mime‐Based Creative Drama Education for Exploring Gesture‐Based User Interfaces

User interfaces that utilise human gestures as input are becoming increasingly prevalent in diverse computing applications. However, few designers possess the deep insight, awareness and experience regarding the nature and usage of gestures in user interfaces to the extent that they are able to exploit the technological affordances and innovate over them. We argue that design students, who will be expected to envision and create such interactions in the future, are constrained as such by their habits that pertain to conventional user interfaces. Design students should gain an understanding of the nature of human gestures and how to use them to add value to UI designs. To this end, we formulated an awareness course' for design students based on concepts derived from mime art and creative drama. We developed the course iteratively through the involvement of three groups of students. The final version of the course was evaluated by incorporating the perspectives of design educators, an industry expert and the students. We present the details of the course, describe the development process, and discuss the insights revealed by the evaluations.