Miracle-dz/UniFAR-FTUs huggingface dataset:
Perspectives from the Innovation and Quality Consortium Induction Working Group on Factors Impacting Clinical Drug-Drug Interactions Resulting from Induction: Focus on Cytochrome 3A Substrates

A recent publication from the Innovation and Quality Consortium Induction Working Group collated a large clinical data set with the goal of evaluating the accuracy of drug-drug interaction (DDI) prediction from in vitro data. Somewhat surprisingly, comparison across studies of the mean- or median-reported area under the curve ratio showed appreciable variability in the magnitude of outcome. This commentary explores the possible drivers of this range of outcomes observed in clinical induction studies. While recommendations on clinical study design are not being proposed, some key observations were informative during the aggregate analysis of clinical data. Although DDI data are often presented using median data, individual data would enable evaluation of how differences in study design, baseline expression, and the number of subjects contribute. Since variability in perpetrator pharmacokinetics (PK) could impact the overall DDI interpretation, should this be routinely captured? Maximal induction was typically observed after 5–7 days of dosing. Thus, when the half-life of the inducer is less than 30 hours, are there benefits to a more standardized study design? A large proportion of CYP3A4 inducers were also CYP3A4 inhibitors and/or inactivators based on in vitro data. In these cases, using CYP3A selective substrates has limitations. More intensive monitoring of changes in area under the curve over time is warranted. With selective CYP3A substrates, the net effect was often inhibition, whereas less selective substrates could discern induction through mechanisms not susceptible to inhibition. The latter included oral contraceptives, which raise concerns of reduced efficacy following induction. Alternative approaches for modeling induction, such as applying biomarkers and physiologically based pharmacokinetic modeling (PBPK), are also considered. Significance Statement The goal of this commentary is to stimulate discussion on whether there are opportunities to optimize clinical drug-drug interaction study design. The overall aim is to reduce, understand and contextualize the variability observed in the magnitude of induction across reported clinical studies. A large clinical CYP3A induction dataset was collected and further analyzed to identify trends and gaps. Reporting individual victim PK data, characterizing perpetrator PK and including additional PK assessments for mixed-mechanism perpetrators may provide insights into how these factors impact differences observed in clinical outcomes. The potential utility of biomarkers and PBPK modeling are discussed in considering future directions.
Attempt to increasing freshness in gluten-free tin bread by adding distilled monoglycerides, α-amylase and glucose oxidase

The market for gluten-free products is still developing and producers seek to offer consumers products as close to standard market products as possible. Therefore, product development of textural and sensory issues in gluten-free bread is crucial for the industry. This experimental explores effects of additives improving freshness of gluten-free bread. From screening of thirteen additives, one emulsifier and two en-zymes where selected, combined and tested at different levels: distilled monoglycer-ides (DMG) from hydrogenated rapeseed oil; a maltogenic α-amylase (AA) and a glucose oxidase (GO). Gluten-free tin bread was used as model recipe. Height, vol-ume and specific volume were negatively affected by DMG. All three additives in-creased the fibre content (resistant starch). Maximum softness was obtained when adding high amount of AA and low amount of DMG. No significant effect on spring-iness was detected. Cohesiveness decreased with raised amounts of AA and DMG. Chewiness correlated with hardness. Sensory evaluation showed divergence regard-ing which attributes mediated ‘freshness’. A harder bread with 0.5% DMG, 125 ppm GO and no AA, was perceived as freshest. This same combination did not get any votes in a ‘squeeze of the loaf’ test. In the latter test, a bread without DMG but 350 ppm AA and 125 ppm GO was most preferred. Despite deviating sensory results, statistically significant results could be obtained: α-amylase increased softness, hence consumer preference, while the emulsifier increase perceived freshness when eating the bread. Consumers are a valuable resource in product development.
Evaluation of the Antibacterial Efficacy of Silver Nanoparticles as an Irrigant against Enterococcus faecalis In vitro Study

Background: Successful root canal therapy depends on thorough chemo mechanical debridement of pulpal tissue, dentin debris and infective microorganisms. Objective: This study aimed to investigate the antibacterial effect of silver nanoparticles, sodium hypochlorite and chlorhexidine in reducing the bacterial infection of the root canals. Materials and Methods: The root canals of 55 single-rooted teeth were cleaned, shaped, and sterilized. All the teeth samples were inoculated with Enterococcus faecalis and incubated at 37°C for 2 weeks. Then, the teeth were divided into four groups. Group I (n=15): 100 ppm silver nanoparticles, Group II (n=15): 2.5 sodium hypochlorite, Group III (n=15): 2% chlorhexidine, IV (n=10): Normal saline as a control group. Specimens were incubated for 2 weeks. Paper points were used to obtain pre- and post-irrigation samples so that the colony-forming units were counted. Data were analyzed using SPSS and tested by Shapiro-Wilk test, One-Way ANOVA and Games-Howell test where the level of significance was set at 0.05. Results: All the tested irrigants showed superior effectiveness compared to the normal saline (p<0.05). Overall, 2.5% sodium hypochlorite presented the most effective action against E. faecalis biofilm, followed by 100 ppm silver nanoparticles, then the 2% chlorhexidine by mean percentage of antibacterial effectiveness of 99.87%, 99.51% and 98.66% respectively. Conclusions: Silver nanoparticles were effective against E. faecalis biofilm similarly to sodium hypochlorite when it was used as an irrigation solution.
Single-molecule investigation of DNA scanning by DNA base repair proteins

In order to preserve genomic stability, cells rely on various repair pathways for removing DNA damage. The mechanisms how enzymes scan DNA and recognize their target sites are incompletely understood. Using high-localization precision microscopy along with 133 Hz high sampling rate, we have recorded EndoV and OGG1 interacting with 12-kbp elongated λ-DNA in an optical trap. EndoV switches between three distinct scanning modes, each with a clear range of activation energy barriers. These results concur with average diffusion rate and occupancy of states determined by a hidden Markov model, allowing us to infer that EndoV confinement occurs when the intercalating wedge motif is involved in rigorous probing of the DNA, while highly mobile EndoV may disengage from a strictly 1D helical diffusion mode and hop along the DNA. This makes EndoV the first example of a monomeric, single-conformation and single-binding-site protein demonstrating the ability to switch between three scanning modes.
In Vitro Evaluation of Remineralizing Effect of Nano-Carbonate Apatite on Demineralized Stripped Enamel Surfaces

Aim: to evaluate the changes of surface hardness and remineralizing effect of nano-carbonate apatite on demineralized stripped enamel surfaces by SEM and micro-hardness examination. Materials and Methods: Forty-five extracted premolars received proximal stripping using diamond coated metal hand-held strip. Each tooth was sectioned by means of a low-speed air and watercooled diamond disc along its major axis into mesial and distal halves i.e. obtaining 90 tooth sections (30 unstripped &60 stripped) and divided into 3 groups: Group A (A1 15 unstripped; A2 15 stripped) served as control. Group B (B1 15 unstripped; B2 15 stripped) specimens were placed in lactic acid for 1h three times a day with 2h preservation in artificial saliva in between for 7 days. Group C (C1 15 unstripped; C215 stripped) specimens were received same treatment as group B then treated with remineralizing agent (APF for C1& n-CAP for C2) immediately after each demineralizing bath. Results: SEM results showed greater demineralization in subgroup B2 compared to B1, while it revealed greater remineralization in subgroup C2 (n-CAP) compared to C1 (APF). Surface microhardness examination results using Mann-Whitney test showed significant decrease in SMH of group B2 compared with (A). SubgroupC1 (APF) showed increase in SMH compared with subgroup B2 with no significant, and decrease compared with group (A). While there was no significant in SMH of subgroup C2 when compared with group (A), however there was highly significant increase in SMH of subgroup (C2) compared with those of subgroup B2 followed by subgroup C1. Conclusion: N-CAP could be considered as a valuable non-fluoride alternative to fluoride containing formulations used for suppressing demineralization and enhancing remineralization of enamel. It can be considered as a potential caries preventive agent showing promise for the recovery of damaged enamel structures.
Mechanisms of Manganese Oxide Electrocatalysts Degradation during Oxygen Reduction and Oxygen Evolution Reactions

Anion-exchange membrane fuel cells and electrolyzers offer a unique opportunity of using non-noble metal electrocatalysts for catalyzing the sluggish oxygen reduction and oxygen evolution reactions (ORR and OER). In recent years, various Mn-based oxides were identified as promising catalysts for both reactions. While electrocatalytic activity of such oxides is well addressed, their stability is still to be proven. Herein, we investigate the stability of four main manganese oxide allotropes by following their Mn dissolution rate in operando ORR and OER conditions. Using an electrochemical on-line inductively coupled plasma mass spectrometer, we uncover unexpected instability of this class of catalysts, with different degradation mechanisms identified under OER and ORR conditions. The reason for their degradation is shown to be related to the production of hydrogen peroxide species on manganese oxides during ORR. Furthermore, we discuss how limits in thermodynamically stable windows of each Mn oxidation sta.
Comparative analysis of charcoal grilling, infrared grilling and superheated steam roasting on the colour, textural quality and heterocyclic aromatic amines of lamb patties

The colour, textural profile and heterocyclic aromatic amines content of lamb patties cooked by charcoal grilling, infrared grilling and superheated steam roasting were investigated. The results of colour showed that lightness and yellowness values were highest in the superheated steam and lowest in charcoal grilled patties. The texture characteristics observed in the superheated steam, and infrared patties were much better. Water loss was highest in charcoal grilled meat. Charcoal grilling produced a significantly (P < 0.05) much higher amount of total HAAs, ranging from 171.26 ng g⁻¹ to 555.29 ng g⁻¹ (polar) and from 200.77 ng g⁻¹ to 426.07 ng g⁻¹ (non‐polar) HAAs, than infrared (39.21 ng g⁻¹ −181.37 ng g⁻¹⁾ and (52.84 ng g⁻¹ −148.59 ng g⁻¹) and superheated steam roasting (from 8.67 ng g⁻¹ to 30.66 ng g⁻¹ and from 23.61 ng g⁻¹ to 89.66 ng g⁻¹⁾ for both types of HAAs in lamb patties. Colour, texture and HAAs were significantly influenced by time and by the temperature used for each cooking method.
Catalytic activity of Fe-modified bentonite in heterogeneous photo-Fenton process

In this study, an easy and inexpensive approach is introduced to synthesize Fe-modified clays for industrial applications. A novel heterogeneous photo-Fenton catalyst was prepared by solid-state ion exchange method. Synthesis of Fe-modified bentonite (Fe-B) was performed at 100°C and 200°C for 0.5, 1, and 2 min. Fe-B was characterized by scanning electron microscopy, elemental dispersive X-ray spectroscopy and X-ray diffraction. The activity of prepared Fe-B catalyst was evaluated in the degradation of methylene blue (MB) in the presence of H2O2 and under UV irradiation. The effects of reaction parameters such as initial dye concentration, H2O2 concentration, Fe-B catalyst loading and initial solution pH on the degradation of MB were also investigated. Between different prepared Fe-B catalysts, the sample prepared at 100°C and 2 min was selected as the optimum conditions for synthesis. Under optimal conditions (pH = 4.0 and 200 ppm H2O2), ~100% discoloration of 200 ppm MB can be achieved in 90 min. The result of two reusability studies on the catalyst for the decolorization of MB was 93.8% and 90.5% after 1st and 2nd reuse, respectively, The result of reusability studies shows the acceptable reusability of the catalyst. These results were satisfactory to recommend Fe-modified bentonite prepared by solid-state ion exchange method as a novel catalyst.
Effect of Putrefaction on Postmortem Detection of Ethanol and Diazepam : An Experimental Study

Drugs and alcohol concentrations are regularly used as evidence in criminal and civil litigations. The interpretation may be critical to the thorough investigations of different types of forensic cases whether antemortem or postmortem. So, the aim of the present work is to study the effect of putrefaction on the postmortem detection of ethanol and diazepam. The study was conducted on 96 adult male albino rats divided randomly to four groups 24 rats for each and every group is further subdivided into 4 subgroups (a, b, c, and d) 6 animals for each subgroup. Group I: control group received 1ml distilled water. Group II: rats received lethal dose of ethanol. Group III: rats received lethal dose of diazepam. Group IV: rats received lethal dose of both ethanol and diazepam. After death of treated animals, control animals were sacrificed at the same time and immediate dissection of subgroup a was done. Rats of subgroups b ,c and d were dissected after death at 18 hours, 24 hours and 48 hours respectively. The livers were extracted for detection of ethanol and diazepam. The control group showed increased liver ethanol in subgroups I-c and I-d. Liver ethanol of group II and IV showed gradual elevation by increasing post mortem interval while there was no considerable change in liver diazepam of group III. As regards liver tissue diazepam of group IV, a non-significant elevation was detected in the subgroups IV-b, IV-c and IV-d as compared to the subgroup IV-a.
Testosterone is Key to Increase the Muscle Capillary Density of Old and Trained Rats

Abstract Introduction It is indicated that aging reduces muscular vascularity. Thus, strategies that aim to reverse or decrease the progression of these changes are suggested. Therefore, the present study aimed to analyze the blood capillary density of the plantaris muscle (PL) of aged rats submitted to strength training and exogenous testosterone use. Methods A total of 30 rats were divided equally into the following groups: EA: 20 months old; OLD: 24 months old; OLD + S: testosterone; ST: strength training; and ST + S: strength training + testosterone. Strength training was performed 3 times a week for 15 weeks. Testosterone administration was performed by the intraperitoneal method 2 times a week at a dose of 10mg/kg. All of the morphological parameters were analyzed using morphoquantitative techniques. Results A significant increase in the capillaries numerical density of the OLD + S and ST + S groups. The OLD + S and ST + S groups demonstrated a higher ratio of capillaries per myofiber than the EA, OLD and ST groups. The OLD and ST groups had a higher ratio than the EA group. The OLD + S, ST and ST + S groups presented a statistically significant increase in the cross-sectional area in the type I fibers when compared with the EA and OLD groups. However, the ST group showed a significant increase compared with the OLD group. In type II fibers, the ST and ST + S groups showed a greater cross-sectional area than the EA group. As for the mean cross-sectional area, the ST and ST + S groups presented significantly larger areas than the other groups. Conclusion Anabolic steroid administration is crucial to increase the blood capillary density of the plantaris muscle of old rats, independently of the effects of strength training.
Toxico‐Metabolomics of Engineered Nanomaterials: Progress and Challenges

Nanoscale matter has unique attributes that potentiate their widespread application from biomedicine, engineering, food, cosmetics, sensing, to energy. Due to the rapid industrialization of engineered nanomaterials (ENMs) as a result of increasing consumer interests, more ENMs will be released into the environment, greatly increasing the probability of their contact with humans. Once these ENMs enter the human body or an ecosystem, they may initiate various biochemical responses in unprecedented ways, thus raising important concerns in regard to their effects on human health and the ecosystem. Here, the shifts in the intricate metabolic pathways instigated by ENMs are highlighted and those altered metabolic changes are extrapolated for the elucidation of environmental health and risk assessment. Furthermore, the toxico‐metabolomics knowledge of ENMs provides the opportunity to design novel nanomedicine with high efficacies by capitalizing on their abilities to rewire metabolic networks for the treatment of diseases.
The Relationship between S. aureus and Branched-Chain Amino Acids Content in Composite Cow Milk

Simple Summary Staphylococcus aureus is not only a common cause of bovine mastitis, but also an agent of food poisoning in humans. S. aureus has the ability to produce branched-chain amino acids (BCAAs) under certain nutritional conditions. We show that levels of two BCCA (leucine and isoleucine) are correlated to the load of S. aureus in composite milk samples. The application of the ANOVA and Tukey-Kramer analysis showed statistically significant differences in the content of the BCAAs, isoleucine and leucine, between the two groups based on S. aureus positivity (p < 0.001), while bivariate Pearson correlation analysis showed a strong relationship between S. aureus load and the content of these two BCAAs. Abstract The early diagnosis of mastitis is an essential factor for the prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. The total amino acid content increases significantly in mastitic milk compared to normal milk. S. aureus requires branched-chain amino acids (BCAAs—isoleucine, leucine, and valine) for protein synthesis, branched-chain fatty acids synthesis, and environmental adaptation by responding to their availability via transcriptional regulators. The increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. The aim of this work is to demonstrate, by a direct ion-pairing reversed-phase method, based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine, and S. aureus load. The correlation coefficient, r, was found to be 0.102 for SCC (p = 0.096), 0.622 for isoleucine (p < 0.0001), 0.586 for leucine (p < 0.0001), 0.013 for valine (p = 0.381), and 0.07 for tyrosine (p = 0.034), standing for a positive correlation between S. aureus and isoleucine and leucine concentration. The link between the content of BCAAs, isoleucine and leucine, and udder infection by S. aureus demonstrated with our study has an important clinical value for the rapid diagnosis of S. aureus mastitis in cows.
Device-Free Crowd Count Estimation Using Passive UHF RFID Technology

Two algorithms using spatial and waveform characteristics are proposed to predict the number of people crossing an existing RFID installation. We show that with some minor additions to the existing systems and using the proposed algorithm, it is possible to estimate the number of people crossing the designated path with reasonably good accuracy. It also does not require tagging of people who are being counted. The proposed idea is tested in the laboratory for continuously moving crowd up to 75 persons, and the count estimation with 90% accuracy has been obtained.
Response of Broiler Chicks to Low-Protein-L-Valine Supplemented Diets Formulated Based on Digestible Amino Acids

The present studywas designed to evaluate the influence of supplementing different levels of L-Valine (L-Val) to low protein diet on chicks' performance, carcass characteristics , digestibility of nutrients andeconomical efficiency. A total number of 640 unsexed day old Arbor Acres meat – type chickswere assigned randomly into 8 equal treatments containing 80 chicks each (10 birds/ replicate). The first group (control) was fed strain recommendation of CP being 23%, 21% and 19% with 0.96, 0.88 and 0.79% digestible valine during starter, grower and finisher periods, respectively (T1). The 2 group was feddiets with a 3% CPless thanthe control, being 20%, 18% and 16% and contained 0.89, 0.79 and 0.69% digestible valine level during the same growth phasesrespectively, as control (T2). Other six groups were fed low–CP diet (LPD) supplemented with 250mg, 500mg, 750mg, 1000 mg, 1250 mg and 1500 mgL-Val/kg diet, respectively. The study lasted for 38 days. The results were as follows:1The best BWG and FCR during overall growth period was achieved by chicks fed the LPD supplemented with 500 mg Val/kg diet, and control group (T1) without significant differences between them.2Valine digestibility was ranged between 91.17 to 97.03%. 3-Control group achieved significantly the lowest abdominal fat percentage as compared to the other groups fed LPD either with or without valine supplementation.4Chicks fed the LPD plus 500 mg Val/kg diet attained the highest means of economic efficiency and its relative value by 103.2% and 114.2% as compared to those fed the recommended protein diet and LPD, respectively. In conclusion, the best level of added Val is 500 mg/kg diet for broilers fed LPDsupplemented with sufficient amount of Methionine, Lysine, Threonine which coincided with the best Val/Lys ratio during starter, grower and finisher periods. Also, it achieved an improvement in economic efficiency and growth performance of broilers.