bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonparametric Methods in Population Pharmacokinetics
Authors: Goutelle Sylvain , Woillard Jean‐Baptiste , Neely Michael , Yamada Walter , Bourguignon Laurent 
Published: October 2020

AbstractPopulation pharmacokinetic (PK) modeling is a widely used approach to analyze PK data obtained from groups of individuals, in both industry and academic research. The approach can also be used to analyze pharmacodynamic (PD) data and pooled PK/PD data. There are 2 main families of population PK methods: parametric and nonparametric. The objectives of this article are to present an overview of nonparametric methods used in population pharmacokinetic modeling and to explain their specific characteristics to inform scientists and clinicians about their potential value for data analysis, simulation, dosage design, and therapeutic drug monitoring (TDM). Nonparametric methods have several interesting characteristics for population PK analysis, including computation of exact likelihoods, the ability to accommodate parameter probability distributions of any shape (eg, non‐Gaussian), and to detect subpopulations and outliers. Nonparametric population methods are also highly relevant for model‐based TDM and design of individualized drug dosage regimens. Several algorithms have been developed to estimate model parameter values within an individual and compute that individual's dosage to achieve target drug exposure with maximum precision and accuracy. Nonparametric modeling methods for both population and individual PK analysis are available under user‐friendly packages.
Water extract of onion catalyst: An economical green route for the synthesis of 2‐substituted and 1,2‐disubstituted benzimidazole derivatives with high selectivity
Authors: Kaliyan Prabakaran , Selvaraj Loganathan , Muthu Seenivasa Perumal 
Published: October 2020

AbstractAn efficient, environmental friendly and substrate controlled method of synthesis of 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 with high selectivity has been achieved from the reaction of o‐phenylenediamine 1 and aldehydes 2 in the presence of water extract of onion and selecting suitable reaction medium. This method is widely applicable for variety of aldehydes such as aromatic/aliphatic/heterocyclic aldehydes and 1,2‐diamines to afford 2‐substituted benzimidazole derivatives 3 and 1,2‐disubstituted benzimidazole derivatives 4 in good to excellent yields (up to 96%). The developed method of water extract of onion catalysis produced 2‐substituted benzimidazoles 3 from aromatic aldehydes having electron‐withdrawing groups, whereas aromatic aldehydes bearing electron donating groups selectively furnished 1,2‐disubstituted benzimidazole 4 derivatives. The process described here has several advantages of cheap, low energy consumption, commercially available starting materials, operational simplicity and nontoxic catalyst. The use of water extract of onion makes this present methodology green and giving a useful contribution to the existing methods available for the preparation of benzimidazole derivatives. In addition, Hammett correlation of substituent constant (σ) vs percentage (%) yield has been established.
Leaching kinetics of electronic waste for the recovery of copper: Rate‐controlling step and rate process in a multisize particle system
Authors: Dávila‐Pulido Gloria I. , Salinas‐Rodríguez Armando , Carrillo‐Pedroza Francisco R. , González‐Ibarra Adrián A. , Méndez‐Nonell Juan , Garza‐García Mitzué 
Published: October 2020

AbstractElectronic waste (e‐waste) contains metallic values that can be recovered by hydrometallurgical methods. This investigation addresses the leaching kinetics of e‐waste for the recovery of copper in H2SO4‐H2O2 media with the objective of determining the rate‐controlling step in monosize particle systems. The results are then used to develop a kinetic model for copper dissolution in multisize particle systems. It is shown that in a monosize particle system, Cu dissolves completely in 150 min at 2 M H2SO4 and 0.2 M H2O2. The rate‐controlling step for this process is chemical reaction with an activation energy of 47.8 kJ/mol. The kinetic model for Cu dissolution in multisize particle systems is developed by applying an optimization method that considers the size distribution and the copper content of each of the size fractions. The results show that the model predicts satisfactorily the Cu dissolution kinetics and reveals that Cu particles with mean sizes of 79, 141, 237, 398.5, and 605 μm react completely in times varying from 15 to 120 min. Coarser Cu particles do not react completely in a time interval of up to 120 min. E‐waste losses 57.6% of its initial weight when subjected to the leaching process and solid residue has gold and silver grades of 2 402.35 and 9 035.29 g/ton, respectively.
Speech Outcomes After Sphincter Pharyngoplasty for Velopharyngeal Insufficiency
Authors: Lam Austin S. , Kirkham Erin M. , Dahl John P. , Kinter Sara L. , Perkins Jonathan A. , Sie Kathleen C.Y. 
Published: October 2020

Objectives/HypothesisTo investigate perceptual speech outcomes following sphincter pharyngoplasty (SP) and to identify patient characteristics associated with velopharyngeal insufficiency (VPI) resolution or improvement.MethodsRetrospective review of prospectively collected data was performed of consecutive patients that underwent SP for management of VPI between 1994 and 2016 at a single tertiary care pediatric hospital. Demographic data, nasendoscopic findings, and speech characteristics were recorded using a standardized protocol. Pre‐ and post‐operative VPI was graded on a five‐point Likert scale. Frequency of post‐operative VPI resolution and improvement was assessed and associations with patient characteristics were analyzed. The association between odds of VPI resolution or improvement and five patient characteristics identified a priori was performed controlling for confounding factors.ResultsTwo‐hundred ninety‐six subjects were included. All patients had at least minimal VPI pre‐operatively; 72% were graded moderate or severe. Sixty‐four percent experienced resolution and 83% improved at least one point on the VPI‐severity scale. Of the five patient characteristics, only history of cleft palate repair was significantly associated with decreased odds of VPI improvement but not resolution when controlling for other variables.ConclusionsSphincter pharyngoplasty resulted in resolution of VPI in 64% and improvement in 83% of subjects. Children with a history of cleft palate had significantly decreased odds of VPI improvement compared to those without a history of cleft palate. Neither syndrome diagnosis nor 22q11 deletion had a significant association with speech outcomes after sphincter pharyngoplasty.Level of Evidence4 Laryngoscope, 131:E2046–E2052, 2021
Tracking Spontaneous Vestibular Schwannoma Regression with Volumetric Measurements
Authors: Patel Evan J. , Deep Nicholas L. , Schecht Michael , Hagiwara Mari , Roland John T. 
Published: October 2020

ObjectiveTo characterize a series of patients with MRI evidence of spontaneous vestibular schwannoma (VS) regression.Study DesignRetrospective case series.MethodsRetrospective review between 2012 and 2020 from a single, tertiary‐care center of all patients with an untreated, sporadic VS and spontaneous regression in volumetric tumor size over the course of observation. The main outcome measures included VS size and location, presenting symptoms, medication use, changes in pure‐tone averages and word recognition scores.ResultsThe 13 treatment‐naïve patients (62% female, mean age 67.1 years) with spontaneous VS regression represented 3.9% of all patients undergoing observation with serial imaging during the study period. Median tumor size from initial MRI was 529.0 mm3 (range: 108 mm3–13,180 mm3). The mean interval between MRI measurements was 5.5 years (SD 4.4 years). The average percent decrease in tumor size was 36.1% (SD 21.9%) and the average rate of volume decrease was 15.8 mm3/yr (SD 25.4 mm3/yr). Five patients were classified as having major regression, defined by a relative decrease in volume of >40%, while eight patients had minor regression (<40% relative volume reduction). No significant differences in initial tumor size, rate of regression, or audiometric changes were observed between the major and minor regression cohorts.ConclusionsPatients with evidence of a spontaneously shrinking VS have a heterogeneous presentation. Due to the scarcity of this phenomenon, predicting which tumors will eventually undergo regression remains unclear. Employing volumetric measurements to compare serial MRI scans may improve the accuracy of detecting shrinking tumors.Level of Evidence4 Laryngoscope, 131:E1647–E1652, 2021
High‐frequency time‐series autonomous observations of sea surface pCO2 and pH
Authors: Wu Yingxu , Dai Minhan , Guo Xianghui , Chen Jinshun , Xu Yi , Dong Xu , Dai Junwei , Zhang Zhirong 
Published: October 2020

AbstractCarbon dioxide partial pressure (pCO2) in surface water was continuously measured every 3 h from July 2012 to June 2013 using an autonomous pCO2 system (MAPCO2) deployed on a moored buoy on the East China Sea shelf (31°N, 124.5°E). Sea surface pCO2 and pH had the largest variations in summer, ranging from 215 to 470 μatm, and 7.941 to 8.263 (averagely 8.084 ± 0.080), respectively. They varied little in winter, ranging from 328 to 395 μatm, and 8.003 to 8.074 (averagely 8.052 ± 0.010), respectively. The seasonal average sea surface pCO2 was respectively 335 ± 70 μatm, 422 ± 43 μatm, 362 ± 11 μatm, and 311 ± 59 μatm in summer, autumn, winter, and spring, and was overall undersaturated with respect to atmosphere on a yearly basis. Although the average sea surface pCO2 in summer was below the atmospheric level, the net CO2 flux has suggested a CO2 source status due to the influence of typhoon. Our observation thus demonstrated the significant, even dominant impact of episodic typhoon events on surface ocean CO2 chemistry and air–sea CO2 gas exchange, which would be impossible to capture by shipboard observation. The high wind stress and curl associated with the northward movement of typhoon induced complex sea surface water movement, vertical mixing, and subsequent biological drawdown, which differed in pre‐, onset, and post‐typhoon stages. Based on our estimates, the degassing fluxes during typhoon reached as high as 82 mmol m−2 CO2 and 242 mmol m−2 CO2 in summer and autumn, respectively, accounting for twice as large as the summer CO2 sink during non‐typhoon period, and 28% of the total CO2 source in autumn.
Larval cross‐shore transport estimated from internal waves with a background flow: The effects of larval vertical position and depth regulation
Authors: Garwood Jessica C. , Lucas Andrew J. , Naughton Perry , Roberts Paul L. D. , Jaffe Jules S. , deGelleke Laura , Franks Peter J. S. 
Published: October 2020

AbstractCross‐shore velocities in the coastal ocean typically vary with depth. The direction and magnitude of transport experienced by meroplanktonic larvae will therefore be influenced by their vertical position. To quantify how swimming behavior and vertical position in internal waves influence larval cross‐shore transport in the shallow (~ 20 m), stratified coastal waters off Southern California, we deployed swarms of novel, subsurface larval mimics, the Mini‐Autonomous Underwater Explorers (M‐AUEs). The M‐AUEs were programmed to maintain a specified depth, and were deployed near a mooring. Transport of the M‐AUEs was predominantly onshore, with average velocities up to 14 cm s−1. To put the M‐AUE deployments into a broader context, we simulated > 500 individual high‐frequency internal waves observed at the mooring over a 14‐d deployment; in each internal wave, we released both depth‐keeping and passive virtual larvae every meter in the vertical. After the waves' passage, depth‐keeping virtual larvae were usually found closer to shore than passive larvae released at the same depth. Near the top of the water column (3–5‐m depth), ~ 20% of internal waves enhanced onshore transport of depth‐keeping virtual larvae by ≥ 50 m, whereas only 1% of waves gave similar enhancements to passive larvae. Our observations and simulations showed that depth‐keeping behavior in high‐frequency internal waves resulted in enhanced onshore transport at the top of the water column, and reduced offshore dispersal at the bottom, compared to being passive. Thus, even weak depth‐keeping may allow larvae to reach nearshore adult habitats more reliably than drifting passively.
Condensed phase corrosion of P91 and DSS 2205 steels at advanced oxygen‐fired pressurized fluidized bed combustion plants
Authors: Li Kaiyang , Zeng Yimin , Luo Jing‐Li 
Published: October 2020

AbstractTo achieve the targets of high energy efficiency and reduced CO2 emission, advanced oxygen‐fired pressurized fluidized bed combustion technology is being developed. The generated flue gas condensates are very corrosive, but very limited information is available to select appropriate alloys for the cost‐effective construction and long‐term safe operation of flue gas components. Thus, this study investigated the corrosion performance of P91 and DSS 2205 steels in the simulated condensates at 60°C–150°C. The dominant reactions on the two steels were considerable oxide formation and high chemical dissolution of the formed oxides instead of localized pitting. The increase in temperature leads to an exponential increase in the long‐term corrosion rates of the steels. Benefited from its high Cr and Mo contents, DSS 2205 steel exhibited much better corrosion resistance, and the formed surface scales consisted of inner Fe‐enriched and outer Cr‐enriched oxides in which Cr2O3 was transformed into Cr(OH)3 with the increase in temperature. The corrosion products on P91 steel consisted of inner Cr–Fr–Mo oxides and outer Fe‐enriched oxides, which were porous and unable to protect the steel.
Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress‐ and aging‐related diseases
Authors: Panossian Alexander G. , Efferth Thomas , Shikov Alexander N. , Pozharitskaya Olga N. , Kuchta Kenny , Mukherjee Pulok K. , Banerjee Subhadip , Heinrich Michael , Wu Wanying , Guo De‐an , Wagner Hildebert 
Published: October 2020

AbstractAdaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress‐induced and aging‐related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine‐immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose‐effect response: at low doses they function as mild stress‐mimetics, which activate the adaptive stress‐response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging‐related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress‐induced and aging‐related diseases.
Recent advances in the design of choline kinase α inhibitors and the molecular basis of their inhibition
Authors: Rubio‐Ruiz Belén , Serrán‐Aguilera Lucía , Hurtado‐Guerrero Ramón , Conejo‐García Ana 
Published: October 2020

AbstractUpregulated choline metabolism, characterized by an increase in phosphocholine (PCho), is a hallmark of oncogenesis and tumor progression. Choline kinase (ChoK), the enzyme responsible for PCho synthesis, has consequently become a promising drug target for cancer therapy and as such a significant number of ChoK inhibitors have been developed over the last few decades. More recently, due to the role of this enzyme in other pathologies, ChoK inhibitors have also been used in new therapeutic approaches against malaria and rheumatoid arthritis. Here, we review research results in the field of ChoKα inhibitors from their synthesis to the molecular basis of their binding mode. Strategies for the development of inhibitors and their selectivity on ChoKα over ChoKβ, the plasticity of the choline‐binding site, the discovery of new exploitable binding sites, and the allosteric properties of this enzyme are highlighted. The outcomes summarized in this review will be a useful guide to develop new multifunctional potent drugs for the treatment of various human diseases.
Phase unwrapping with a rapid opensource minimum spanning tree algorithm (ROMEO)
Authors: Dymerska Barbara , Eckstein Korbinian , Bachrata Beata , Siow Bernard , Trattnig Siegfried , Shmueli Karin , Robinson Simon Daniel 
Published: October 2020

PurposeTo develop a rapid and accurate MRI phase‐unwrapping technique for challenging phase topographies encountered at high magnetic fields, around metal implants, or postoperative cavities, which is sufficiently fast to be applied to large‐group studies including Quantitative Susceptibility Mapping and functional MRI (with phase‐based distortion correction).MethodsThe proposed path‐following phase‐unwrapping algorithm, ROMEO, estimates the coherence of the signal both in space—using MRI magnitude and phase information—and over time, assuming approximately linear temporal phase evolution. This information is combined to form a quality map that guides the unwrapping along a 3D path through the object using a computationally efficient minimum spanning tree algorithm. ROMEO was tested against the two most commonly used exact phase‐unwrapping methods, PRELUDE and BEST PATH, in simulated topographies and at several field strengths: in 3T and 7T in vivo human head images and 9.4T ex vivo rat head images.ResultsROMEO was more reliable than PRELUDE and BEST PATH, yielding unwrapping results with excellent temporal stability for multi‐echo or multi‐time‐point data. It does not require image masking and delivers results within seconds, even in large, highly wrapped multi‐echo data sets (eg, 9 seconds for a 7T head data set with 31 echoes and a 208 × 208 × 96 matrix size).ConclusionOverall, ROMEO was both faster and more accurate than PRELUDE and BEST PATH, delivering exact results within seconds, which is well below typical image acquisition times, enabling potential on‐console application.
Numerical solutions for solving model time‐fractionalFokker–Planckequation
Authors: Mahdy Amr M. S. 
Published: October 2020

AbstractIn this work, we use two different techniques to discuss approximate analytical solutions for the time‐fractional Fokker–Planck equation (TFFPE), namely the new iterative method (NIM) and the fractional power series method (FPSM). Stability analyses and truncation errors are studied using a procedure like the fundamental von Neumann stability analysis. Discretization is carried out numerically for TFFPE by the implicit finite difference and the Crank–Nicolson method. The techniques used in solving the TFFPE are simple and powerful enough to understand the numerical solutions of linear and nonlinear fractional differential equations. We discuss the approximate solutions obtained using the NIM and FPSM. This is explained by employing tables and shapes. The approximate solutions strongly converge to an accurate solution. All computations in this work were carried out using Maple 16.
R‐weak commutativity, examples, and applications
Authors: Kutukcu Servet 
Published: October 2020

AbstractThe aim of this article is to define a new contraction and its variants in non‐Archimedean Menger probabilistic metric‐spaces, and utilize them to establish the existence of a combined common fixed point illustrating with examples. We also apply our result to integral type equations, Volterra type integral equations, damped harmonic oscillators, and nonlinear matrix equations.
Soret–Dufour mechanism on an electrically conducting nanofluid flow past a semi‐infinite porous plate with buoyancy force and chemical reaction influence
Authors: Falodun Bidemi O. , Ayegbusi Florence D. 
Published: October 2020

AbstractThis study explored the flow of an electrically conducting and chemically reacting nanofluid over a semi‐infinite porous vertical plate under the influence of Soret–Dufour and nonlinear buoyancy force. The flow analysis consists of partial differential equations (PDEs). These equations were nondimensionalized via nondimensional quantities into coupled nonlinear PDE and solved numerically using spectral relaxation method. Numerical computations of all flow parameters for velocity, temperature along with concentration are presented in diagrams. The result shows that an upsurge in the value of the radiation parameter enhances both velocities along with temperature profiles, respectively. This is true because the temperature at the plate is much when there is an increase in the radiation parameter. The present results were compared with the previously published result and were found to be in excellent agreement.
Emerging Immunotherapies in the Treatment of Brain Metastases
Authors: Nieblas-Bedolla Edwin , Nayyar Naema , Singh Mohini , Sullivan Ryan J. , Brastianos Priscilla K. 
Published: October 2020

Abstract

Brain metastases account for considerable morbidity and mortality in patients with cancer. Despite increasing prevalence, limited therapeutic options exist. Recent advances in our understanding of the molecular and cellular underpinnings of the tumor immune microenvironment and the immune evasive mechanisms employed by tumor cells have shed light on how immunotherapies may provide therapeutic benefit to patients. The development and evolution of immunotherapy continue to show promise for the treatment of brain metastases. Positive outcomes have been observed in several studies evaluating the efficacy and safety of these treatments. However, many challenges persist in the application of immunotherapies to brain metastases. This review discusses the potential benefits and challenges in the development and use of checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and oncolytic viruses for the treatment of brain metastases. Future studies are necessary to further evaluate and assess the potential use of each of these therapies in this setting. As we gain more knowledge regarding the role immunotherapies may play in the treatment of brain metastases, it is important to consider how these treatments may guide clinical decision making for clinicians and the impact they may have on patients.

Implications for Practice
Immunotherapies have produced clinically significant outcomes in early clinical trials evaluating patients with brain metastases or demonstrated promising results in preclinical models. Checkpoint inhibitors have been the most common immunotherapy studied to date in the setting of brain metastases, but novel approaches that can harness the immune system to contain and eliminate cancer cells are currently under investigation and may soon become more common in the clinical setting. An understanding of these evolving therapies may be useful in determining how the future management and treatment of brain metastases among patients with cancer will continue to advance.