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Abstract Extraction of nucleic acids (NAs) is critical for many methods in molecular biology and bioanalytical chemistry. NA extraction has been extensively studied and optimized for a wide range of applications and its importance to society has significantly increased. The COVID-19 pandemic highlighted the importance of early and efficient NA testing, for which NA extraction is a critical analytical step prior to the detection by methods like polymerase chain reaction. This study explores simple, new approaches to extraction using engineered smart nanomaterials, namely NA-binding, intrinsically disordered proteins (IDPs), that undergo triggered liquid–liquid phase separation (LLPS). Two types of NA-binding IDPs are studied, both based on genetically engineered elastin-like polypeptides (ELPs), model IDPs that exhibit a lower critical solution temperature in water and can be designed to exhibit LLPS at desired temperatures in a variety of biological solutions. We show that ELP fusion proteins with natural NA-binding domains can be used to extract DNA and RNA from physiologically relevant solutions. We further show that LLPS of pH responsive ELPs that incorporate histidine in their sequences can be used for both binding, extraction and release of NAs from biological solutions, and can be used to detect SARS-CoV-2 RNA in samples from COVID-positive patients.

Abstract Cellular response to redox imbalance is crucial for organismal health. microRNAs are implicated in stress responses. ALG-1, the C. elegans ortholog of human AGO2, plays an essential role in microRNA processing and function. Here we investigated the mechanisms governing ALG-1 expression in C. elegans and the players controlling lifespan and stress resistance downstream of ALG-1. We show that upregulation of ALG-1 is a shared feature in conditions linked to increased longevity (e.g., germline-deficient glp-1 mutants). ALG-1 knockdown reduces lifespan and oxidative stress resistance, while overexpression enhances survival against pro-oxidant agents but not heat or reductive stress. R02D3.7 represses alg-1 expression, impacting oxidative stress resistance at least in part via ALG-1. microRNAs upregulated in glp-1 mutants (miR-87-3p, miR-230-3p, and miR-235-3p) can target genes in the protein disulfide isomerase pathway and protect against oxidative stress. This study unveils a tightly regulated network involving transcription factors and microRNAs which controls organisms’ ability to withstand oxidative stress.

Objective: Treatment decisions in neovascular age-related macular degeneration (nAMD) are mainly based on subjective evaluation of OCT. The purpose of this cross-sectional study was to provide a comparison of qualitative and quantitative differences between OCT devices in a systematic manner. Design: Prospective, cross-sectional study. Subjects: One hundred sixty OCT volumes, 40 eyes of 40 patients with nAMD. Methods: Patients from clinical practice were imaged with 4 different OCT devices during one visit: (1) Spectralis Heidelberg; (2) Cirrus; (3) Topcon Maestro2; and (4) Topcon Triton. Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were manually annotated in all cubes by trained human experts to establish fluid measurements based on expert-reader annotations. Intraretinal fluid, SRF, and PED volume were quantified in nanoliters (nL). Bland–Altman plots were created to analyze the agreement of measurements in the central 1 and 6 mm. The Friedman test was performed to test for significant differences in the central 1, 3, and 6 mm. Main Outcome Measures: Intraretinal fluid, SRF, and PED volume. Results: In the central 6 mm, there was a trend toward higher IRF and PED volumes in Spectralis images compared with the other devices and no differences in SRF volume. In the central 1 mm, the standard deviation of the differences ranged from ± 3 nL to ± 6 nL for IRF, from ± 3 nL to ± 4 nL for SRF, and from ± 7 nL to ± 10 nL for PED in all pairwise comparisons. Manually annotated IRF and SRF volumes showed no significant differences in the central 1 mm. Conclusions: Fluid volume quantification achieved excellent reliability in all 3 retinal compartments on images obtained from 4 OCT devices, particularly for clinically relevant IRF and SRF values. Although fluid volume quantification is reliable in all 4 OCT devices, switching OCT devices might lead to deviating fluid volume measurements with higher agreement in the central 1 mm compared with the central 6 mm, with highest agreement for SRF volume in the central 1 mm. Understanding device-dependent differences is essential for expanding the interpretation and implementation of pixel-wise fluid volume measurements in clinical practice and in clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract We investigated the dynamics of Bose–Einstein condensates (BECs) under an external periodic potential. We consider two such systems, the first being made of exciton–polaritons in a nanoribbon of transition metal dichalcogenides (TMDCs), such as MoSe $$_2$$ 2 , embedded in a microcavity with a spatial curvature, which serves as the source of the external periodic potential. The second, made of bare excitons in a nanoribbon of twisted TMDC bilayer, which naturally creates a periodic Moiré potential that can be controlled by the twist angle. We proved that such systems behave as semiclassical time crystals (TCs). This was demonstrated by the fact that the calculated BEC spatial density profile shows a non-trivial long-range two-point correlator that oscillates in time. These BECs density profiles were calculated by solving the quantum Lindblad master equations for the density matrix within the mean-field approximation. We then go beyond the usual mean-field approach by adding a stochastic term to the master equation which corresponds to quantum corrections. We show that the TC phase is still present.

Background: DNA methylation patterns are directly associated with diverse metabolic disorders. The status of methyl-donor micronutrients has been associated with DNA methylation levels, and altered ingestion of folate, choline, betaine, B vitamins and methionine may impact genes both globally and at the level of promoter regions. Despite this, the role of methyl-donor micronutrient supplementation on DNA methylation profiles is currently unclear. Objectives: The aims of this systematic review and meta-analysis were to identify and synthesize the evidence about methyl-donor nutrient supplementation on DNA methylation. Methods: A systematic literature search was performed in Medline, Embase, Scopus, and Web of Science databases with a combination of terms related to DNA methylation assessment, supplementation, and methyl-donor nutrients. Studies (in vitro, animal models, or human clinical trials) were included if DNA methylation levels after any kind of methyl-donor micronutrient supplementation or treatment was investigated. Studies were assessed for bias using Revised Cochrane risk-of-bias tool for randomized trials, risk-of-bias in Non-randomized Studies of Interventions or Systematic Review Centre for Laboratory Animal Experimentation tools. Data were extracted from studies measuring DNA methylation levels in any sample or tissue, following any kind of methyl-donor micronutrient supplementation or treatment. Separate random-effects meta-analyses were performed for animal model studies and human clinical trials that examined the effects of folic acid supplementation on DNA methylation. Results: Fifty-seven studies were included in this systematic review: 18 human clinical trials, 35 in animal model, and 4 in vitro studies. Concerning overall risk of bias, most of the studies were classified as “high risk” or “some concerns.” Meta-analysis with meta-regression from studies in animal models showed that folic acid dose significantly affected DNA methylation and that high and very high doses showed increases in DNA methylation when compared to low doses. However, meta-analysis of human clinical trials showed that folic acid supplementation did not promote significant changes in DNA methylation when compared to placebo. Conclusion: Folic acid supplementation may change global DNA methylation levels in animals supplemented with high, as compared to low, doses. Heterogeneity in studies and supplementation protocols make it difficult to establish clinical recommendations. However, these effects, even if small, might be of clinical importance in the management of patients with diseases related to DNA hypomethylation.

Collaboration is a part of the music industry and has increased over recent decades; but little do we know about its effects on success and evolution. Our goal is to analyze how success has evolved over collaboration networks and compare its global scenario to a local, thriving one: the Brazilian music industry. Specifically, we build collaboration networks from data collected from Spotify's Global and Brazilian daily charts, analyze them and identify collaboration profiles in such networks. Analyses over their topological characteristics reveal collaboration patterns mapped into four different profiles: Standard, Niche, Ephemeral and Absent, where the two first have a higher level of success. Furthermore, we do deeper by evaluating the temporal evolution of such profiles through case studies: pop and k-pop globally, and pop and forró in Brazil. Overall, our findings emphasize the importance of collaboration profiles in assessing success, and show differences between the global and Brazilian scenarios.

In Brazil, bidding processes constitute the main method through which the Public Administration acquires goods and services, and they aim to select the best proposal between several bidding companies. Analyzing public bids can reveal several negotiating characteristics between companies and the public sector, including alerts of fraudulent activities involving such businesses. This article presents two approaches for detecting irregularities within small companies using data extracted from public bids in the Brazilian state of Minas Gerais. For each approach, we perform exploratory and geospatial analysis to better understand specific characteristics of the companies with irregularity alerts. Furthermore, we execute a network analysis to examine the underlying connections between such companies. Our findings reveal the efficacy of both approaches in indicating small companies that may be involved in fraudulent activities. Our methodology and results represent a significant advance for the public sector as they have the potential to enhance mechanisms for overseeing and preventing fraud within bidding processes.

Analyzing overpricing in public bidding items is essential for government agencies to detect signs of fraud in acquiring public goods and services. In this context, this paper presents two main contributions: a methodology for processing and standardizing bid item descriptions and a statistical approach for overpricing detection using the interquartile range. We evaluated a comparative analysis of three distinct grouping strategies, each emphasizing different facets of the item description standardization process. Furthermore, to gauge the efficacy of both proposed approaches, we leveraged a ground-truth dataset for a thorough evaluation containing quantitative and qualitative analyses. Overall, our findings suggest that the evaluated strategies are promising for identifying potential irregularities within public bidding processes.

Abstract This study estimated biomass and carbon from components, future carbon values and to obtain economic productive value of carbon fixation of a Seasonal Semideciduous Forest. Biomass and carbon were estimated using adjusted equations and selected using regression statistics. The prognosis of the diametric distribution was performed using the movement ratio method. In the economic evaluation, it was estimated productive value of the stand, referring to the current and future carbon fixation capacity. The coefficients of determination (adjusted R²) of the equations ranged from 0.11 to 0.90 and the standard error of the estimate (Syx) ranged from 41.53% to 141.89% for the biomass of the components, and from 0.03 to 0.87 for adjusted R² and from 46.20% to 143.64% for the error, for stored carbon in the components. The total biomass of the tree component estimated was 56.25 t ha-1 and 25.88 t ha-1 of total carbon. Using the future distributions by the method of the ratio of movements, total stored carbon (aerial + roots) estimated was 14.44 t. ha-1 over the 20-year period. The productive value for the fragment reached R$ 299.95 per ha. year-1.

Category: Ankle; Sports Introduction/Purpose: A growing body of evidence favors the use of dynamic fixation techniques such as suture endo button over rigid screw fixation for syndesmotic injuries. However, specific dynamic fixation techniques have been poorly evaluated. The purpose of this study was to compare single suture-endobutton fixation (single) to double fixation with suture-endobuttons placed one centimeter (cm) apart (double 1 cm) and double fixation with suture-endobuttons placed three cm apart (double 3 cm). Methods: Twenty-four lower leg specimens from twelve cadavers were tested using a custom biaxial apparatus. Internal rotation, external rotation, and anterior and posterior translation of the tibia and fibula were examined using motion tracking systems after transection of deltoid and syndesmotic ligaments to compare three syndesmotic repair techniques: 1) a single suture-endobutton placed 1 cm above the joint line, 2) two suture suture-endobuttons placed 2 and 3 cm above the joint line, and 3) two suture- endobuttons placed 1 and 4 cm above the joint line. Results: All three endobutton constructs improved the stability of the syndesmosis by reducing aberrant motion after transection. There was no clear superiority of either single suture-endobutton (SEB), double suture-endobuttons placed 2 and 3 cm above the joint line (DSEB 1), or double suture-endobuttons placed 1 and 4 cm above the joint line (DSEB 3). DSEB 3 and DSEB 1 showed equal median laxity for tibia internal rotation (2.7 degrees, DSEB 1 (2.0 – 3.2) degrees, DSEB 3 (2.3 – 2.8) degrees), tibia external rotation (-0.2 degrees, DSEB 1 (-0.4 - 0.4) degrees, DSEB 3 (-0.4 - 0.3) degrees), and fibula external rotation (-0.3 degrees, DSEB 1 (-0.7 - 0.3) degrees, DSEB 3 (-0.7 - 0.7) degrees). Conclusion: Cadaveric biomechanical studies are critical to evaluate various suture-endobutton constructs prior to widespread use in patients. Our results demonstrate that the added cost of a second suture-endobutton may not confer substantial additional stability to the syndesmosis. Likewise, increased spread between suture-endobuttons appears to have minimal impact of syndesmotic stability.

Abstract Background Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life. Methods Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life. Discussion The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover. Trial registration The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4 . Registered on 21 January 2019.

Key points Although an overall boon to clinical diagnosis, increasingly voluminous, diverse, and fragmented diagnostic data can overwhelm physicians and frustrate patients. Data are gathered and processed within “silos” of the diagnostic disciplines, including radiology and pathology. The EHR does little to intelligently organize and synthesize these disparate data to facilitate diagnosis. ID envisions a process in which data from the entire arsenal of in vivo and in vitro diagnostics, together with clinical data from the EHR, are aggregated and contextualized to enhance diagnosis and direct clinical action

Many researchers presume greater variability between female participants than between males due to the menstrual cycle. This view has encouraged a sex bias in health and medical research, resulting in considerable knowledge gaps with important clinical implications. Yet in another field—evolutionary biology—the received wisdom is the reverse: that men are more variable, possibly due to male heterogamety. To test these competing hypotheses, we compared variance between the sexes for 50 morphological and physiological traits, analysing data from the NHANES database. Nearly half the traits did not exhibit sexual dimorphism in variation, while 18 exhibited greater female variation (GFV), indicating GFV does not dominate human characteristics. Only eight traits exhibited greater male variation (GMV), indicating GMV also does not dominate, and in turn offering scant support for the heterogamety hypothesis. When our analysis was filtered to include only women with regular menstrual cycles (and men of equivalent age), the number of traits with GFV and GMV were low and not statistically different, suggesting that the menstrual cycle does not typically explain GFV when it occurs. In practical terms, health and medical researchers should no longer simply assume that female participants will induce additional variation in the traits of interest.

In a streaming-oriented era, predicting which songs will be successful is a significant challenge for the music industry. Indeed, there are many efforts in determining the driving factors that contribute to a song’s success, and one potential solution could be incorporating artistic collaborations, as it allows for a wider audience reach. Therefore, we propose a multi-perspective approach that includes collaboration between artists as a factor for hit song prediction. Specifically, by combining online data from Billboard and Spotify, we tackle the problem as both classification and hit song placement tasks, applying five different model variants. Our results show that relying only on music-related features is not enough, whereas models that also consider collaboration features produce better results.

ABSTRACT Laboratory chemical analysis of leaf samples can be costly and time-consuming, making it impractical for assessing crop variability. To address this challenge, researchers have focused on developing non-invasive tools that aid nitrogen (N) management, maximizing profits, minimizing environmental impact, and meeting market demands. This study aimed to develop a computer vision-based classifier system for assessing the N status in bean crops. An experiment was conducted in a greenhouse, involving five treatments (0%, 50%, 100%, 150%, and 200% N of the recommended dose) with six replications, totaling 30 pots containing six seedlings of Phaseolus vulgaris L. beans in four different phenological phases (V4, R5, R6, and R7). Digital RGB images of the bean canopies were captured using a camera at four-week intervals (30, 37, 44, and 51 days after emergence - DAE). The images were manually labeled to create an image database based on N status. Four different computational N status classifiers were developed by training a Convolutional Neural Network (CNN), one for each DAE. The classifiers were evaluated using confusion matrix metrics (accuracy, precision, and recall), resulting in an overall accuracy of about 80% when evaluating nitrogen status at five levels. Improved results were achieved by grouping the saturation classes of the 150% and 200% treatments with the 100% class (>=100% class), yielding an accuracy of 97% for 30 and 44 DAE. Promising results aside, this method opens new possibilities for improvement and application to other treatments, electromagnetic spectrum bands, and crops.

The COVID-19 pandemic impacts on eating habits among adolescents may be more relevant in pediatric patients with immunocompromised chronic diseases. This case-control study conducted between June and October 2020 aimed to: (i) describe dietary patterns of adolescents with chronic conditions compared to healthy controls and (ii) determine associations between food consumption, health-related quality of life (HRQL) and sleep quality during the COVID-19 pandemic. Participants (184 immunocompromised and 58 healthy adolescents, aged 14.3 [SD 2.5]) responded to HRQL and sleep validated instruments (PedsQL and PSQI) and three 24 h food recalls via online software. Adjusted linear and logistic regressions were used to assess differences in dietary patterns and associations between food consumption (according to Nova classification) and HRQL and sleep quality. Adolescents with gastrohepatic, rheumatic, and kidney diseases had an improved dietary pattern vs. their healthy peers, showing greater consumption of unprocessed and minimally processed foods (unstandardized coefficient (b) = 7.35%[95%CI 1.59; 13.1]; b = 15.10%[95%CI 7.00; 23.1]; and b = 11.2%[95%CI 5.68; 16.8]), and lower consumption of ultraprocessed foods (b = −7.53%[95%CI-12.90; −2.18]; b = −11.4%[95%CI-18.90; −3.94]; b = −10.8%[95%CI-16.00; −5.68]). Consumption of culinary ingredients was associated with reduced psychological HRQL in controls (standardized coefficient (β) = −0.26[95%CI-0.52; −0.004]), and processed food consumption was associated with improved sleep latency in immunocompromised participants (β = 0.16[95%CI 0.01; 0.31]). These findings suggest diet quality may play a role in HRQL and sleep quality in this population, and may be relevant for clinical practitioners and policy makers when considering the importance of dietary quality in immunocompromised youths.

Background: Although there is a low incidence of shoulder instability in women, this population is still representative and is often associated with lower rates of return to sports. Few studies have evaluated the results of the Latarjet procedure in this population. Methods: This was a prospective cohort study of female athletes who underwent the Latarjet procedure between 2013 and 2018. The participants were followed up for 3 years. The primary outcomes of the study included the visual analog scale for pain; range of motion: active elevation, passive elevation, active external rotation, and passive external rotation. The functional scores were as follows: American Shoulder and Elbow Surgeons score, the Western Ontario Shoulder Instability Index, and the Athletic Shoulder Outcome Rating Scale. Additional data were collected regarding return to sport, complication rates, and patient satisfaction. Results: Thirteen female athletes who practice Soccer, Volleyball, Basketball, Handball, Judo, or Weight training were evaluated. There was a significant reduction in the mean range of motion for all movements at 4 weeks after surgery. Patients recovered a range of motion similar to the preoperative values after 6 months. The mean visual analog scale reached 6.39 at the first week after surgery and decreased to values below preop at 8 weeks. The mean preoperative Western Ontario Shoulder Instability Index was 126.77 (min 118; max 135), and at the end of follow-up, the WOSI index was 45.08 (min 37; max 65; P

Abstract Drug‐drug interaction (DDI) is an important consideration for clinical decision making in prostate cancer treatment. The objective of this study was to evaluate the effect of enzalutamide, an oral androgen receptor inhibitor, on the pharmacokinetics (PK) of digoxin (P‐glycoprotein [P‐gp] probe substrate) and rosuvastatin (breast cancer resistance protein [BCRP] probe substrate) in men with metastatic castration‐resistant prostate cancer (mCRPC). This was a phase I, open‐label, fixed‐sequence, crossover study (NCT04094519). Eligible men with mCRPC received a single dose of transporter probe cocktail containing 0.25 mg digoxin and 10 mg rosuvastatin plus enzalutamide placebo‐to‐match on day 1. On day 8, patients started 160 mg enzalutamide once daily through day 71. On day 64, patients also received a single dose of the cocktail. The primary end points were digoxin and rosuvastatin plasma maximum concentration (Cmax), area under the concentration‐time curve from the time of dosing to the last measurable concentration (AUClast), and AUC from the time of dosing extrapolated to time infinity (AUCinf). Secondary end points were enzalutamide and N‐desmethyl enzalutamide (metabolite) plasma Cmax, AUC during a dosing interval, where tau is the length of the dosing interval (AUCtau), and concentration immediately prior to dosing at multiple dosing (Ctrough). When administered with enzalutamide, there was a 17% increase in Cmax, 29% increase in AUClast, and 33% increase in AUCinf of plasma digoxin compared to digoxin alone, indicating that enzalutamide is a “mild” inhibitor of P‐gp. No PK interaction was observed between enzalutamide and rosuvastatin (BCRP probe substrate). The PK of enzalutamide and N‐desmethyl enzalutamide were in agreement with previously reported data. The potential for transporter‐mediated DDI between enzalutamide and digoxin and rosuvastatin is low in men with prostate cancer. Therefore, concomitant administration of enzalutamide with medications that are substrates for P‐gp and BCRP does not require dose adjustment in this patient population.

Since artificial intelligence (AI) is extensively used in the field of education, it presents various opportunities in teaching and learning. In education, AI is chiefly used to impart knowledge, stimulate comprehension, heighten intelligence, and is treasured as support in learning. It is also instrumental in empowering and inspiring students. The emergence of AI also has a positive impact on inclusive education. Because these technologies can potentially transform teaching and learning, it is important to understand how they can be used to further support inclusive education. This non-empirical research analyzed some advantages and challenges of incorporating AI in teaching and learning and highlighted how it influences inclusion. Based on the literature, some of the advantages of AI are improved performance of students, motivation, and encouragement of students. This review also identified some challenges associated with the use of AI for inclusive education, such as technological difficulties, poor connectivity, pedagogical issues, and limitations of the database. Some recommendations are proposed to address these challenges. This research can assist educators, parents, students, government officials, and policymakers in making proper decisions on the effective use of AI and inclusion.

Several studies have shown the development of electrochemical biosensors based on enzymes immobilized in metal–organic frameworks (MOFs). Although enzymes have unique properties, such as efficiency, selectivity, and environmental sustainability, when immobilized, these properties are improved, presenting significant potential for several biotechnological applications. Using MOFs as matrices for enzyme immobilization has been considered a promising strategy due to their many advantages compared to other supporting materials, such as larger surface areas, higher porosity rates, and better stability. Biosensors are analytical tools that use a bioactive element and a transducer for the detection/quantification of biochemical substances in the most varied applications and areas, in particular, food, agriculture, pharmaceutical, and medical. This review will present novel insights on the construction of biosensors with materials based on MOFs. Herein, we have been highlighted the use of MOF for biosensing for biomedical, food safety, and environmental monitoring areas. Additionally, different methods by which immobilizations are performed in MOFs and their main advantages and disadvantages are presented.

Given the lack of investments, structure, and difficulty of metabolite isolation, promising natural product studies do not progress to preclinical studies, such as pharmacokinetics. 2′-Hydroxyflavanone (2HF) is a flavonoid that has shown promising results in different types of cancer and leishmaniasis. For accurate quantification of 2HF in BALB/c mouse blood, a validated HPLC-MS/MS method was developed. Chromatographic analysis was performed using C18 (5μm, 150 mm × 4.6 mm). The mobile phase consisted of water containing 0.1% formic acid, acetonitrile, and methanol (35/52/13 v/v/v) at a flow rate and total running time of 0.8 mL/min and 5.50 min, respectively, with an injection volume of 20 µL. 2HF was detected by electrospray ionization in negative mode (ESI-) using multiple reaction monitoring (MRM). The validated bioanalytical method showed satisfactory selectivity without significant interference for the 2HF and IS. In addition, the concentration range between 1 and 250 ng/mL showed good linearity (r = 0.9969). The method showed satisfactory results for the matrix effect. Precision and accuracy intervals varied between 1.89% and 6.76% and 95.27% and 100.77%, respectively, fitting the criteria. No degradation of 2HF in the biological matrix was observed since stability under freezing and thawing conditions, short duration, postprocessing, and long duration showed deviations less than 15%. Once validated, the method was successfully applied in a 2HF oral pharmacokinetic study with mouse blood, and the pharmacokinetic parameters were determined. 2HF demonstrated a Cmax of 185.86 ng/mL, a Tmax of 5 min, and a half-life (T1/2) of 97.52 min.

Glass surfaces play a critical role in several modern applications, and open questions remain as to how the bulk composition of a multicomponent glass informs its surface composition—particularly at the outermost monolayer. This has important implications for properties such as electrostatic charging, wetting, and adhesion. Here, we apply high-sensitivity low-energy ion scattering (HS-LEIS) to examine a systematic series of ternary CaO-Al2O3-SiO2 glass compositions. Analyzed are fresh fracture surfaces created under high-vacuum conditions, giving rigorous attention to peak quantification details. Results indicate that the measured surface compositions are, within uncertainty, very close to analyzed bulk compositions. This finding runs contrary to many studies showing disagreement between surface and bulk composition in glass, and possible reasons are discussed. By providing an experimental foundation from relatively ideal fracture surfaces, these results pave the way for further studies on the outermost composition of realistic glass surfaces of commercial importance.