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A silver carbonate-based method to synthesize benzoxazoles from imines has been developed. The reaction is extremely mild, tolerates several heterocycles and functional groups, and provides highly functionalized benzoxazoles in modest to good yields. The reaction proceeds in an array of solvents and atmospheric conditions, demonstrating the robustness of this oxidation method and its ability to provide an alternative method for the easy preparation and isolation of these bioactive compounds.

The research work covered the in vitro establishment of Persian lime nodal segments using a twig disinfection protocol, and their culture on Murashige and Skoog (MS) culture media supplemented with antibiotics (Estrepto-Ler® and Rifampicin) and fungicide (Chlorothalonil). The axillary buds production was performed cultured the nodal segments without contamination signs on MS culture media enriched with two cytokinins (6-BAP and Kinetin) at different concentrations. Results showed that 52 % of the nodal segments did not show signs of in vitro contamination when the twig submerged in 20% chlorine for 15 min during disinfection process and nodal segments were grown in MS culture medium supplemented with 2 mg L-1 of Rifampicin and fungicide Chlorothalonil. Interestingly, MS culture medium enriched with 6-BAP (0.5 mg L-1) + Kinetin (0.5 mg L-1) turned out to be the best combination to achieve that 78 % of nodal segments promoted 1 to 2 axillary buds.

OBJECTIVE The goal of this article is to present the analysis of anti-abatacept antibody data from children with polyarticular-course juvenile idiopathic arthritis (pJIA), treated with abatacept. The data are from 395 participants with pJIA from two abatacept registrational trials. METHODS We analyzed immunogenicity data according to age groups, administration route (intravenous [IV] or subcutaneous [SC]), drug treatment interruption, and co-medications (with or without methotrexate [MTX]) to assess impact on the incidence of anti-abatacept antibodies. RESULTS The overall immunogenicity incidences observed in both JIA trials ranged between 4.7% and 23.3%. There was a slightly higher immunogenicity incidence in the 2-5-year-old participants (15.2%) compared with 6-17-year-old participants (4.7%). In the study with SC dosing, the overall incidence on treatment was 2.3% (3% if co-dosed with MTX), similar to the incidence for Period A of the IV study (similar duration of treatment as the SC study), which was 2.1% (1.4% if co-dosed with MTX). In the IV study, the period following a 6-month interruption in treatment had comparable immunogenicity incidences (22.9% with interruption vs. 18.2% without interruption, both co-dosed with MTX and 0% for both not co-dosed with MTX). In most cases, participants co-dosed with MTX had higher immunogenicity incidences than those on abatacept alone. CONCLUSION Although some trends were noted in terms of incidence according to age and MTX co-dosing, none where conclusive owing to differences in population size. Drug holiday had no impact on immunogenicity incidence once treatment was resumed, and incidences across SC and IV dosing were comparable. There was no impact of immunogenicity on pharmacokinetics, safety, and efficacy.

We report small-sample evidence from a randomized experiment among a set of urban Ecuadorian households who owned both electric induction and gas stoves. We randomly assigned households to cook only with one stove during a prescribed two-day monitoring period, and then cook only with the other stove in a subsequent two-day period. The order of stove use was randomized, and air pollution was measured during each period. We found that mean 48-hour personal NO2exposure was 9.9 ppb higher (95% CI, 4.5-15.3) — a 50% increase over the 48-hour induction mean — when households were randomized to gas as compared to induction. Mean kitchen area NO2concentrations were 1 ppb higher (95% CI, 0.4-2.1) (a 6% increase) and mean personal PM2.5exposure was 11μgm−3higher (95% CI, -0.1-22.8) (a 44% increase) during study periods when randomized to gas. We use time-resolved cooking and pollution data to illustrate that these differences are driven by LPG cooking, which was associated with a 5.0 ppb increase in 5-minute average NO2kitchen area concentrations (95% CI, 3.4-6.7) and a 20.8μgm−3increase in 5-minute average personal PM2.5exposure (95% CI 8.9-32.6). In contrast, cooking with induction was not associated with changes to short-term NO2kitchen area concentrations, though it was associated with short-term increased personal PM2.5exposure (10.8, 95% CI, 5.7-15.9).

Electrophilicity (

In this study, Crocin, Digitoxigenin, Beta-Eudesmol, and Favipiravir were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). The docking study was followed by Molecular Dynamics simulation. The result indicates that Crocin and Digitoxigenin are the structures with the best affinity in the studied enzyme's binding site. Still, Molecular Dynamics simulation showed that Digitoxigenin is the molecule that fits better in the active site of the main protease. Therefore, this molecule could have a more potent antiviral treatment of COVID-19 than the other three studied compounds. © 2021 by the authors.

We determined the optical profiles of a molecular system coupled with a thermal bath in presence of intramolecular coupling. Solvent effects were explicitly considered as a random variable by model...

The selenoenzyme glutathione peroxidase (GPx) like activity of stable organoselenium compounds has been evaluated through the initial rate (ν0) of the reduction reaction of H2O2, Cum-OOH, and t-BuO...

Breast cancer is the main cancer type with more than 2.2 million cases in 2020, and is the principal cause of death in women; with 685000 deaths in 2020 worldwide. The estrogen receptor is involved at least in 70% of breast cancer diagnoses, and the agonist and antagonist properties of the drug in this receptor play a pivotal role in the control of this illness. This work evaluated the agonist and antagonist mechanisms of 30 cannabinoids by employing molecular docking and dynamic simulations. Compounds with docking scores -8 kcal/mol were analyzed by molecular dynamic simulation at 300 ns, and relevant insights are given about the protein's structural changes, centered on the helicity in alpha-helices H3, H8, H11, and H12. Cannabicitran was the cannabinoid that presented the best relative binding-free energy (-34.96 kcal/mol), and based on rational modification, we found a new natural-based compound with relative binding-free energy (-44.83 kcal/mol) better than the controls hydroxytamoxifen and acolbifen. Structure modifications that could increase biological activity are suggested.

Primary hyperoxaluria type 1 (PHT1) treatment is mainly focused on inhibiting the enzyme glycolate oxidase, which plays a pivotal role in the production of glyoxylate, which undergoes oxidation to produce oxalate. When the renal secretion capacity exceeds, calcium oxalate forms stones that accumulate in the kidneys. In this respect, detailed QSAR analysis, molecular docking, and dynamics simulations of a series of inhibitors containing glycolic, glyoxylic, and salicylic acid groups have been performed employing different regression machine learning techniques. Three robust models with less than 9 descriptors—based on a tenfold cross (Q2CV) and external (Q2EXT) validation—were found i.e., MLR1 (Q2CV = 0.893, Q2EXT = 0.897), RF1 (Q2CV = 0.889, Q2EXT = 0.907), and IBK1 (Q2CV = 0.891, Q2EXT = 0.907). An ensemble model was built by averaging the predicted pIC50 of the three models, obtaining a Q2EXT = 0.933. Physicochemical properties such as charge, electronegativity, hardness, softness, van der Waals volume, and polarizability were considered as attributes to build the models. To get more insight into the potential biological activity of the compouds studied herein, docking and dynamic analysis were carried out, finding the hydrophobic and polar residues show important interactions with the ligands. A screening of the DrugBank database V.5.1.7 was performed, leading to the proposal of seven commercial drugs within the applicability domain of the models, that can be suggested as possible PHT1 treatment.

Within-tree variation of four handsheet properties (burst index, sheet density, STFI short-span compression strength (STFI) and tensile index) was mapped for loblolly pine trees aged 13 and 22 years using NIR predicted handsheet property data (representing an average of 18 trees for each age). All within-tree maps were similar demonstrating a radial decrease in handsheet properties at all heights, with sheet density and tensile index having the greatest within-tree variation. The corewood zone had the highest values for all properties, while the lowest values were observed in a region consistent with juvenile and transitional outerwood as defined by Burdon et al. (2004). The maps are also similar to, but the inverse of, maps reported in prior studies for density and tracheid coarseness and wall thickness. Relationships amongst the examined handsheet properties and wood and tracheid properties explains the overall similarities of the different maps. The maps provide a representation of within-tree variation of important paper properties at two different ages. An understanding of how these properties vary within loblolly pine trees can aid in better utilization of forest resources.

In the present work, the fast amide bond cleavage of [3-((1R,5S,7s)-3-azabicyclo[3.3.1]nonane-7-carbonyl)-3-azabicyclo[3.3.1]nonane-7-carboxylic acid (bi-ATDO)], through an intramolecular nucleophilic attack of an amine group is evaluated. First, six possible peptide bond cleavage mechanisms, two of them including a water molecule, are described at the ωB97XD/6-311 + G(d,p)//MP2/6-311 + G(d,p) level of theory. The reaction consisting of an intramolecular nitrogen nucleophilic attack followed by a proton transfer and the amide bond cleavage is determined as the most favorable mechanism. The activation free energy computed for the latter is 20.5 kcal mol-1 , which agrees with the reported experimental result of 24.8 kcal mol-1 . Inclusion of a water molecule to assist the first step of the reaction results in an activation free energy increase of about 17 kcal mol-1 . All the steps in the most favorable mechanism are studied more in detail employing intrinsic reaction coordinate as well as the reaction force and reaction electronic flux analysis.

A new phosphole derivative, 2,5-di(2-quinolyl)-1-phenylphosphole (1), was synthesized by using the Fagan–Nugent method. Phosphole 1 was obtained as an air-stable solid in high yield (73%). Addition...

Biodiesel from four different renewable resources was produced. An optimization of the reference methodology by gas chromatography was conducted based on the construction of calibration curves for each biodiesel during fatty acid methyl esters (FAME) quantification. Therefore, in the proposed optimized methodology, pure commercial standards are not necessary. Consequently, a reduction in the research expenses is achieved, making this methodology a cost-effective alternative for FAME quantification. The calibration curves obtained for each biodiesel presented slope values between 0.5–0.7 and regression coefficients (R2) > 0.98 in all cases. These results were compared to those obtained by the conventional methodology. With respect to the validation of the optimized methodology, a comparison of the results obtained by this proposed methodology and the reference one is presented. Finally, a robust and promising technique to quantify FAME present in biodiesel was successfully developed in this study.

BACKGROUND AND AIMS Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P

Maps developed using Akima’s interpolation method, and representing average data for trees aged 13 and 22 years, were used to compare patterns of within-tree variation for Pinus taeda L. (loblolly pine) tracheid properties: coarseness (C), specific surface (S), radial (R) and tangential (T) diameter and wall thickness (w). SilviScan-calibrated near-infrared (NIR) spectroscopy provided data for the analysis with C (Rc2 = 0.85, Rp2 = 0.85), S (Rc2 = 0.83, Rp2 = 0.76), and w (Rc2 = 0.89, Rp2 = 0.93) models having very good calibration / prediction statistics, while those for T and R diameter were moderate (Rc2 = 0.79, Rp2 = 0.57) and poor (Rc2 = 0.64, Rp2 = 0.19), respectively. C, S, and w maps were similar to the density maps for P. taeda and indicate the properties increase radially at all heights. The T diameter map was similar to maps reported for microfibril angle except that T diameter increased radially and with height whereas microfibril angle decreased radially and with height. The map for R diameter increased with height and was unlike the other properties examined; caution is recommended regarding any interpretations based on the R diameter map owing to the weak statistics observed for the NIR model. Changes observed between the two ages are consistent with the asymptotic progression of properties associated with maturation.

Aim: To present the reader with different approaches used to compare immunogenicity methods when changes are needed during a clinical program. Results: Five case studies are presented, in the first two case studies, the approach utilized a small sample size for the comparison. In the third case, all samples from a study were analyzed by both methods. In the fourth case, the intended use of noncomparable assays in an integrated summary drove design of experiments to establish the expected limits of pooling data. In the fifth case, a selectivity approach was used as an alternate to use of incurred samples. Conclusion: When data pooling across methods is needed, it is important to define the limits of comparability.

[Resumen] Objetivo. Valorar en individuos con lesión medular traumática (LMT) la relación entre la mortalidad y la necesidad de UCI y las alteraciones objetivadas mediante resonancia magnética (RM) precoz, analizando alteraciones parenquimatosas, disrupción de ligamentos vertebrales (DLV) y compresión del cordón medular (CCM). Diseño. Estudio retrospectivo. Ámbito. Hospital de tercer nivel, unidad de lesionados medulares y UCI. Pacientes. Individuos con LMT aguda entre los años 2010 y 2019. Intervenciones. Análisis de RM realizada en las primeras 72 horas. Variables de interés. Ingreso en UCI y mortalidad. Resultados. Recogidos 269 casos. El patrón que se asoció a una mayor mortalidad fue la hemorragia (16,7%) por 12,5% de los edemas a un nivel y 6,5% de los edemas a múltiples niveles (p = 0,125). Lo mismo aconteció con los ingresos en UCI: 69,0% en hemorragia por 60,2% en edema múltiple y 46,3% en edemas cortos (p = 0,018). Con respecto a la CCM, la mortalidad fue del 13,4% con 59,2% de ingresos en UCI por 2,2% y 42,2% de quienes no presentaban compresión (p = 0,020 y p = 0,003). Las cifras de éxitus e ingreso en UCI en los individuos con DLV fueron del 15,0% y el 67,3%, respectivamente, por un 6,2% y 44,4% de los individuos sin DLV (p < 0,001 y p = 0,013). Conclusiones. La presencia de hemorragia medular, CCM y DLV se asoció a una mayor necesidad de UCI. Existe un significativo aumento de la mortalidad en los casos con CCM y DLV. [Abstract] Objective. To assess in individuals with traumatic spinal cord injury (TSCI) the relationship between mortality and need for ICU and early magnetic resonance imaging (MRI), analyzing spinal parenchymal alterations, disruption of vertebral ligaments (DVL) and spinal cord compression (SCC). Design. Retrospective study. Setting. Third-level hospital, Spinal Cord Injury Unit and ICU. Patients. Individuals with acute TSCI between 2010 and 2019. Intervention. Analysis of MRI performed in the first 72 h. Variables of interest. Admission to ICU and mortality. Results. 269 cases collected. The pattern that demonstrated higher mortality was cord hemorrhage (16.7%) for 12.5% of single-level edema and 6.5% of multilevel edema (p = 0.125). The same happened with ICU admissions: 69.0% in hemorrhage, 60.2% in multilevel edema and 46.3% in short edema (p = 0.018). Analyzing CCM, mortality was 13.4% with 59.2% of ICU admissions, for 2.2% and 42.2% of individuals without cord compression (p = 0.020 and p = 0.003). The figures of death and ICU admission among cord injuries with DVL were 15.0% and 67.3%, for 6.2% and 44.4% of the individuals without DLV (p < 0.001 and p = 0.013). Conclusions. The presence of spinal cord hemorrhage, SCC and DVL was associated with a higher admission in ICU. A significant increase in mortality was observed in cases with SCC and DVL.

Microbial biofilms cause several environmental and industrial issues, even affecting human health. Although they have long represented a threat due to their resistance to antibiotics, there are currently no approved antibiofilm agents for clinical treatments. The multi-functionality of antimicrobial peptides (AMPs), including their antibiofilm activity and their potential to target multiple microbes, has motivated the synthesis of AMPs and their relatives for developing antibiofilm agents for clinical purposes. Antibiofilm peptides (ABFPs) have been organized in databases that have allowed the building of prediction tools which have assisted in the discovery/design of new antibiofilm agents. However, the complex network approach has not yet been explored as an assistant tool for this aim. Herein, a kind of similarity network called the half-space proximal network (HSPN) is applied to represent/analyze the chemical space of ABFPs, aiming to identify privileged scaffolds for the development of next-generation antimicrobials that are able to target both planktonic and biofilm microbial forms. Such analyses also considered the metadata associated with the ABFPs, such as origin, other activities, targets, etc., in which the relationships were projected by multilayer networks called metadata networks (METNs). From the complex networks’ mining, a reduced but informative set of 66 ABFPs was extracted, representing the original antibiofilm space. This subset contained the most central to atypical ABFPs, some of them having the desired properties for developing next-generation antimicrobials. Therefore, this subset is advisable for assisting the search for/design of both new antibiofilms and antimicrobial agents. The provided ABFP motifs list, discovered within the HSPN communities, is also useful for the same purpose.

This research reported a hydrogel loaded with the ethanolic and methanolic extracts of Eupatorium glutinosum Lam. The E. glutinosum extracts were characterized by phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), and UV/Vis profile identification. This research also evaluated the pharmacological activity of the extracts using antimicrobial, antioxidant, and anti-inflammatory assays prior to polymeric encapsulation. Results indicate that extracts inhibit the Escherichia colii DH5-α (Gram negative) growth; excellent antioxidant activity was evaluated by the ferric reducing power and total antioxidant activity assays, and extracts showed an anti-hemolytic effect. Moreover, the cotton and microcrystalline cellulose hydrogels demonstrate successful encapsulation based on characterization and kinetics studies such as FTIR, extract release, and swelling degree. Moreover, effective antibacterial activity was registered by the loaded hydrogel. The overall results encourage and show that Eupatorium glutinosum-loaded hydrogel may find a wide range of bandage and wound healing applications in the biomedical area.

Correlations among Shimura’s parameter (dCo) from spectrochemical series for 34 ligands and electronic descriptors from density functional theory calculations are reported. Simple and multiple linear regression models were constructed. The best results were obtained with the descriptors estimated with MN15 functional, obtaining a multiple linear regression model based on a quantitative structure–property relationship (QSPR) approach, with four attributes and the statistical parameters: R2 = 0.8543, Q2LOO = 0.8050, and Q2LMO = 0.7977. The four molecular descriptors are ligand field splitting (Δ), dipole moment (χC), enthalpy of the metal complex (HC) and the ligand HOMO energy (EHO_L). This model obtained for the Ni(0) complexes represents a novel approach to the spectroscopic series description based on computational tools also revising the models proposed from Werner’s description until modern recompilations carried out across the spectroscopic series developments. The applicability of the model was evaluated on cooper complexes and good prediction of the dCo values for some ligands was also obtained.

The nature of the Na⋯B bond, in the recently synthesized NaBH 3- adduct, is analyzed on the light of the Na- propensity to polarize along the bond axis as a consequence of the electric field produced by the BH3 fragment. The observed induced polarization has two consequences: (i) the energetic stabilization of the Na- , and (ii) the split of its valence electrons into two opposite lobes along the bond axis. Additionally, an analysis of the electron localization is presented using the information content of the correlated conditional pair density that reveals a significant delocalization between one lobe of the polarized Na- anion and the BH3 fragment at the equilibrium distance. Our findings reported here complement previous works on this system.

The topological profiles of the nonlinear optical properties of a two-level molecular system involving simplified versions of intramolecular coupling immersed in a thermal reservoir have been studied in four-wave mixing (FWM) spectroscopy. Solvent effects have been explicitly considered by modeling the nonradiative interaction with the solute as a random variable. To formulate a solution, it is necessary to introduce stochastic considerations. We assume that system–solvent interactions induce random shifts in the Bohr frequency of the adiabatic states, and their manifestation corresponds to the broadening of the upper level. The Born–Oppenheimer (BO) electronic energy curves for this molecular model consist of two intertwined harmonic oscillator potentials shifted in both their position and their minimum equilibrium energy. The critical quantities for this analysis are the transition and permanent dipole moments, which depend strongly on intramolecular coupling. Our results show how absorption and refractive index are affected by vibronic coupling and solvent stochasticity.

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a–e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-β-D-ribose-2’-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of −71.3 to −12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a–e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

Increased added sugar consumption is associated with type II diabetes, metabolic syndrome, and cardiovascular disease. Low and no-calorie alternative sweeteners have long been used as an aid in the reduction of added sugar. Unfortunately, these alternative sweeteners often have notable sensory deficits when compared to sucrose. Furthermore, many alternative sweeteners have synthetic origins, while consumers are increasingly turning to foods from natural origins, and from more sustainable sources. Such sweeteners include the rare sugar allulose, which can be manufactured from common agricultural waste and dairy co-product streams, and is reported to have a sensory profile similar to sucrose. This study aimed to determine the influence of the rare sugar allulose on consumer perception of sweetened vanilla yogurt. Participants were recruited to evaluate 4 vanilla yogurts sweetened with either sucrose, allulose, stevia or sucralose, and to rate their liking of the samples overall, and for flavor, texture, and their purchase intent. Statistical analysis of hedonic data from 100 consumers suggested that allulose performed similarly to sucrose in liking and purchase intent, and superior to other sweeteners tested in this study, with fewer off-flavors. Moreover, when consumers were queried on their purchase intent after learning details on the sweetener for each formulation, allulose scored significantly higher than all other formulations in purchase intent. This study highlights the potential of the rare sugar allulose as a low calorie, zero glycemic index, natural and better tasting sugar replacement in sweetened yogurt.

The nature of the Na⋯B bond, in the recently synthesized NaBH

The goal of this article is to present the analysis of anti-abatacept antibody data from children with polyarticular-course juvenile idiopathic arthritis (pJIA), treated with abatacept. The data are from 395 participants with pJIA from two abatacept registrational trials.We analyzed immunogenicity data according to age groups, administration route (intravenous [IV] or subcutaneous [SC]), drug treatment interruption, and co-medications (with or without methotrexate [MTX]) to assess impact on the incidence of anti-abatacept antibodies.The overall immunogenicity incidences observed in both JIA trials ranged between 4.7% and 23.3%. There was a slightly higher immunogenicity incidence in the 2-5-year-old participants (15.2%) compared with 6-17-year-old participants (4.7%). In the study with SC dosing, the overall incidence on treatment was 2.3% (3% if co-dosed with MTX), similar to the incidence for Period A of the IV study (similar duration of treatment as the SC study), which was 2.1% (1.4% if co-dosed with MTX). In the IV study, the period following a 6-month interruption in treatment had comparable immunogenicity incidences (22.9% with interruption vs. 18.2% without interruption, both co-dosed with MTX and 0% for both not co-dosed with MTX). In most cases, participants co-dosed with MTX had higher immunogenicity incidences than those on abatacept alone.Although some trends were noted in terms of incidence according to age and MTX co-dosing, none where conclusive owing to differences in population size. Drug holiday had no impact on immunogenicity incidence once treatment was resumed, and incidences across SC and IV dosing were comparable. There was no impact of immunogenicity on pharmacokinetics, safety, and efficacy.

Technetium-99m macroaggregated albumin is used to estimate lung shunt fraction (LSF) prior to yttrium-90 (Y90). Studies have debated the safety and efficacy of Y90 in patients with LSF > 15%. We aimed to assess the role of Y90 in hepatocellular carcinoma (HCC) with LSF > 15%. With IRB approval, we searched our prospectively acquired database of HCC patients with Y90 treated with LSF > 15%. Median LSF and liver and lung doses were calculated. The response was assessed using RECIST. Overall survival (OS) was calculated from date of first Y90. A total of 103 HCC patients underwent Y90. The median baseline LSF was 24.4% (IQR 18.1–28.8). Patients exhibited multifocal disease (59/103, 60%) and median tumor size of 7.85 cm (IQR 5.2, 10.57). BCLC class was A, B, C, and D in 7 (7%), 5 (5%), 85 (83%), and 6 (6%) patients, respectively. The median liver dose was 84.6 Gy (IQR 57.4, 107.55). The median lung dose per session and cumulatively was 22.9 Gy (IQR 15–28) and 29.5 Gy (IQR 20.5–44.3). Thirty-three patients (32%) demonstrated partial response, 57 stable disease, and 13 (13%) had progressive disease. The median OS was 7.3 months (95% CI 5.3, 11.47). Twenty patients (19%) had non-specific pulmonary symptoms (cough, shortness of breath, wheezing) in the 1-year post-Y90. The median time to the appearance of non-specific pulmonary symptoms was 63 days (range 7–224). Thoracic imaging demonstrated no pulmonary fibrosis/injury following treatment in any patient. Y90 can be performed in patients with LSF > 15%. The RECIST response was identified in 32% of the patients. In isolation, LSF > 15% should not deter from treatment with Y90.

Near-infrared (NIR) spectra or NIR-hyperspectral images obtained from radial strips or wood discs provide a cost-effective methodology for examining wood property variation within trees. The calibration used for wood property prediction is critical and can be obtained using two fundamentally different approaches. One involves using a spatial-specific model where wood property data and corresponding spectral data are measured at the same resolution for calibration and prediction, e.g. 10-mm radial increments. The other provides a spatial-interpolated model and involves measuring a property on a broad-scale, e.g. whole-tree, calibrating this data against NIR spectra representing the equivalent scale and then using the calibration to predict the property at higher resolution. To understand the impact of these approaches on subsequent patterns of within-tree variation, whole-tree air-dry density (ADD) and coarseness maps, based on data obtained using the two different approaches, were compared. Patterns of ADD and coarseness variation were comparable indicating that both approaches can be utilized to examine within-tree variation. Spatial-interpolated models have a distinct advantage; being based on whole-tree (or disc) samples, they greatly reduce the cost of wood property analysis and allow the development of maps for properties that are costly and difficult to measure, for example, pulp yield.

Osteoporosis is a highly prevalent disease with important consequences. The most widely used drugs to control this disease are bisphosphonates but their prolonged use is associated with the risk of atypical fractures. We report the cases of two patients under bisphosphonate treatment with bilateral atypical femoral fractures. In one patient the fractures occurred simultaneously, unprovoked by trauma, and in the other, they occurred as delayed fractures after mild trauma. In both cases, the fractures were preceded by pain. The fractures were treated with intramedullary nailing and bisphosphonate withdrawal with good outcomes. Although bisphosphonates have demonstrated effectiveness in preventing frailty-related fractures, their prolonged use has paradoxically been associated with atypical fractures. These fractures are usually preceded by pain. Consequently, when faced with this clinical picture, physicians should request imaging studies that could show incomplete fractures that could benefit from prophylactic nailing before becoming complete fractures.

To investigate laboratory parameters as predictors of overall survival (OS) for hepatocellular carcinoma (HCC) treated with radioembolization and develop/validate a scoring system.With IRB approval, we included all patients with baseline alpha-fetoprotein (AFP) 100 ng/dL from our prospectively acquired HCC radioembolization database. Neutrophil-lymphocyte ratio, albumin-bilirubin (ALBI), and AFP were measured at baseline and at 1-, 3-, and 6-month post-radioembolization Landmarks. OS was assessed from these Landmarks. Univariate/multivariate analyses were performed to evaluate OS predictability of these parameters. Baseline Imaging, Laboratory, and Combination scoring systems were developed. Developing/validating groups were created to investigate/validate the score's OS predictability. Time-dependent receiver operating characteristics (ROC) were evaluated. Patients were stratified into groups I, II, and III by using 25th and 75th percentile cutoffs according to change in Laboratory Score from baseline.345/401 (86%), 238/401 (59%), and 167/401 (42%) patients had laboratory parameters available at the 1-, 3-, and 6-month Landmarks, respectively. ALBI and AFP were significant OS prognosticators at all Landmarks. The Laboratory Score [ALBI + (0.3 × LnAFP)] was developed/internally validated to predict OS from these Landmarks. Areas under the curve of time-dependent ROCs of the Baseline Imaging vs. Laboratory scores in predicting patient OS post 3 and 6 months Landmarks were 0.56 versus 0.82 and 0.57 versus 0.77, respectively. OS differences in groups I, II, and III according to change in Laboratory Score from baseline were significant (p 0.001).Post-radioembolization AFP and ALBI scores were significant OS prognosticators. A decrease in post-therapeutic Laboratory Score, which combines AFP and ALBI, correlates with an improved OS.

The occurrence, persistence, and accumulation of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) represent a new environmental problem due to their harmful effects on human and aquatic life. A suitable absorbent for a particular type of pollutant does not necessarily absorb other types of compounds, so knowing the compatibility between a particular pollutant and a potential absorbent before experimentation seems to be fundamental. In this work, the molecular interactions between some pharmaceuticals (amoxicillin, ibuprofen, and tetracycline derivatives) with two potential absorbers, chitosan and graphene oxide models (pyrene, GO-1, and coronene, GO-2), were studied using the ωB97X-D/6-311G(2d,p) level of theory. The energetic interaction order found was amoxicillin/chitosan &gt, amoxicillin/GO-1 &gt, amoxicillin/GO-2 &gt, ibuprofen/chitosan &gt, ibuprofen/GO-2 &gt, ibuprofen/GO-1, the negative sign for the interaction energy in all complex formations confirms good compatibility, while the size of Eint between 24–34 kcal/mol indicates physisorption processes. moreover, the free energies of complex formation were negative, confirming the spontaneity of the processes. The larger interaction of amoxicillin GOs, compared to ibuprofen GOs, is consistent with previously reported experimental results, demonstrating the exceptional predictability of these methods. The second-order perturbation theory analysis shows that the amoxicillin complexes are mainly driven by hydrogen bonds, while van der Waals interactions with chitosan and hydrophobic interactions with graphene oxides are modelled for the ibuprofen complexes. Energy decomposition analysis (EDA) shows that electrostatic energy is a major contributor to the stabilization energy in all cases. The results obtained in this work promote the use of graphene oxides and chitosan as potential adsorbents for the removal of these emerging pollutants from water.

Funding Acknowledgements Type of funding sources: None. Introduction In acute infarction myocardial and cardiogenic shock, the shock index (SI) has been associated with poor prognostic in recent researches, but its relation with haemodynamic parameters has not been described. Purpose Evaluate relation between SI and measures of cardiac output by pulmonary artery catheter in cardiogenic shock. Methods Prospective study of older than 18 years and admitted for cardiogenic shock in two cardiovascular critical units. Included patient with pulmonary artery catheter for cardiac output estimated. Excluded patient with cardiac index (CI)always greater than 2.2 ml/min/m2. The measures were performed with standard protocol. In the moment was perform measures, we were calculated the shock index and cardiac power output (CPO). It has been definite as an altered value a SI ≥0.8 CI ≤2.2 and CPO ≤0.6. We have calculated sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood ratio (-LH). In addition, we have searched a linear relation with Pearson correlation coefficient. Result 95 measures of cardiac output were performed. Rhythm during measurements was 75.7% (n = 72) in sinus rhythm, 9.4% (n = 9) in nodal rhythm and 4.2% (n = 4) in atrial fibrillation. Treatments during measurements were 68.5% (n = 24) with norepinephrine, 17.8% (n = 17) with epinephrine, 10.5% (n = 10) with vasopressin, 6.31% (n = 6) with dexmedetomidine, and 27.3% (n = 26) with amiodarone. Only 7.3% (n = 7) measures were in context of recent use of beta-block (24 horas before). CI average was 2.36 (0.9-3.71), CPO average was 0.72 (0.25-1.29) and SI average was 0.8 (0.4-1.5). The relation between SI and CI: sensitivity 64.1% (95% CI 47.1-78.8%), specificity 48.2% (95% CI 34.7-619%), +LR 1.24 (95% CI 0.9-1.7), -LR 0.74 (95% CI 0.45-1.23) and Pearson correlation coefficient -0.175. The relation between SI and CPO: sensitivity 63.3% (95% CI 43.9-80%), specificity 46.2% (33.7-60%), +LR 1.18 (0.83-1.67), -LR 0.79 (0.46-1.36) and Pearson correlation coefficient -0.166. Subsequently, the analysis of relation between SI and CI after excluded nodal rhythm, atrial fibrillation, recent use of beta-block, and use of dexmedetomidine and/or amiodarone was: sensitivity 87.5% (95% CI 61.7-98.5%), specificity 43.6% (27.8-60.4%), +LR 1.55 (1.11-2.16), -LR 0.29 (0.07-1.1) and Pearson correlation coefficient -0.49. The relation between SI and CPO after excluded the same aforementioned variables was: sensitivity 25% (95% CI 12.1-42.2%), specificity 94.7% (74-99.8%), +LR 4.75 (0.65-34.74), -LR 0.0.79 (0.64-0.98) and Pearson correlation coefficient -0.55. Conclusion In the general sample, we did not find a linear relation between SI and CI or CPO. By excluding aforementioned variables, we founded a relation between a normal SI and CI >2.2, and between an abnormal SI and CPO ≤0.6. There could be additional variables to cardiac output that explain the relation between SI and poor prognosis. Better validation requires a larger sample.