Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways.However,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse reactions.Therefore,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different TKIs.This paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(VA-DSPE)achieved since 2017.It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing techniques.In addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Caliper-based precise positioning of the target(CALIPPOT)for transcranial magnetic stimulation without neuronavigation system

To the editor:Transcranial magnetic stimulation(TMS)is a non-invasive brain modulation technique.One important usage of TMS is the transient interruption of cognitive brain function(also named virtual lesion)for investigating precisely where and when a specific cortical region contributes to a specific cognitive function.1 A more important usage of TMS is the treatment of brain disorders by repetitive TMS(rTMS).

Possible Habitats for NH_(3),NH_(2)D,H^(13)CN,HC^(15)N,SO,and C^(18)O in the Initial Conditions of High-mass Star Formation

The initial condition of high-mass star formation is a complex area of study because of the high densities(n_(H_(2))>106cm^(-3))and low temperatures(T_(dust)<18 K)involved.Under such conditions,many molecules become depleted from the gas phase by freezing out onto dust grains.However,the N-bearing and deuterated species could remain gaseous under these extreme conditions,suggesting that they may serve as ideal tracers.In this paper,using the Plateau de Bure Interferometer and Very Large Array observations at 1.3 mm,3.5 mm,and 1.3 cm,we investigate the possible habitats for NH_(3),NH_(2)D,H^(13)CN,HC^(15)N,SO,and C^(18)O in eight massive precluster and protocluster clumps G18.17,G18.21,G23.97N,G23.98,G23.44,G23.97S,G25.38,and G25.71.We found that the NH3cores are in good agreement with the 3.5 mm peak emission,but the NH_(3)is much more extended than the 3.5 mm emission structure.The SO distributions agree well with the 3.5 mm peaks for the evolved star formation stage,but we did not detect any SO emission in the four earliest star formation sources.C^(18)O is a poor tracer in conditions of the cold(■18 K)and dense(■10^(4)cm^(-3))cores,e.g.,the prestellar cores.We also found that the NH_(2)D cores are mainly located in the temperature range of 13.0-20.0 K,and the NH_(2)D lines may be strongly depleted above 20 K.

Impact of auditory stimulation nursing protocol on auditory response in cerebrovascular stroke patients

Objectives:The objective of the study was to explore the impact of auditory stimulation protocol on auditory response in cerebrovascular stroke(CVS)patients.Materials and Methods:A pre-posttest nonequivalent control group quasi-experimental study was conducted at Al Mainal Hospital at Al Kars Einy Hospital,Cairo University,among 60 CVS patients,and the sample was randomly assigned through a coin to allocate subjects to study or control group(30 for each group).Auditory stimulation techniques were applied three times per week for the study group for two consecutive weeks.Patients in the control group received only routine hospital care during the study period.The Glasgow Coma Scale(GCS)score for assessing the neurological function and level of arousal and the auditory subscale score of Western Neuro Sensory Stimulation Profile(WNSSP)for assessing auditory response were recorded and compared between the two groups before and after the intervention.Results:There were statistically significant differences between the study group and the control group regarding third reading of GCS score(11.5±0.3 vs.10.6±0.9,t=4.676,P=0.000).The scores of all auditory subscales of WNSSP in the study groups increased after implementing the auditory stimulation protocol(P<0.05).Conclusion:Utilizing the auditory stimulation protocol by nurse proves to be an effective method for enhancing hearing responses in individuals with CVS.

Methods of Variations and Their Applications

In this review article, we begin with reviewing Calculus of variations giving few examples on its use to solve a large number of problems in geometry, physics, and other branches of knowledge. Afterwards, we direct our attention to different methods of variations which evolved during the last century and which include their use in eigenvalue problems and in finite difference methods and those adopted in classical and quantum mechanics. The methods used in evaluating products and quotients of functionals are also discussed along with variational iteration methods. Later on, a good number of applications in different areas are presented and discussed;then a concluding discussion is given.

Effectiveness of one-to-one feedback methods of teaching with proper metered-dose inhaler technique and correcting errors in chronic obstructive lung disease patients

Objective:To determine the most common mistakes made during the use of a metered-dose inhaler(MDI),and the effect of the repeated trainings performed with demonstration method by providing one-to-one feedback on these mistakes.Methods:This is a quasi-experimental study with a control group.A total of 100 chronic obstructive pulmonary disease(COPD)patients(50 in the control group and 50 in the experimental group)were included in the research.“Patient Information Form(PIF)”(to determine the descriptive characteristics of patients)through the face-to-face interview method,using“MDI Skill Assessment Form”(MDISAF)(it is composed of 10 skill steps about the use of MDI)through observation method was used.Patients in both the groups were asked to use MDI and their abilities regarding use of MDI were assessed.Then in the intervention group,usage of MDI was explained by a nurse via demonstration and placebo MDI.Trainings were repeated on days 1,3,and 5 as from hospitalization of the patient.In the intervention group,three methods were used in this study:“face-to-face training,”“one-to-one,”and“with feedbacks and repeated.”Routine training regarding use of MDI was given by the nurses in the clinic to patients in the control group.The use of an MDI was assessed using MDISAF before training and after the training on the first,third and fifth days of hospitalization.On the seventh day,the last measurement was performed.Percentage,chi square,and mean were used to assess the data.Results:After repetitive training with one-to-one feedback,several differences between the groups in favor of the experimental group were found in 7 of the 10 skill levels of the MDI.There was a significant difference after“training”between the groups in the third,fourth,fifth,sixth,seventh,eighth and ninth MDI steps in posttest measurement(P<0.05).Evaluating the skills of the groups to use MDI from pretest to posttest,it was determined that while the intervention group made less mistakes in steps in which mistakes were made mostly,the control group continued to make mistakes.Conclusions:Inhaler technique intervention with repeated,face to face,and one-to-one feedback trainings can significantly enhance the MDI techniques in COPD patients.The patients in the intervention group made less mistakes during MDI application and their application skills improved.It may be asser ted that the training provided to the intervention group was effective for using the device correctly,while the training provided in the clinic for the control group was inadequate.

The State-of-the-Art Review on Applications of Intrusive Sensing,Image Processing Techniques,and Machine Learning Methods in Pavement Monitoring and Analysis

In modern transportation,pavement is one of the most important civil infrastructures for the movement of vehicles and pedestrians.Pavement service quality and service life are of great importance for civil engineers as they directly affect the regular service for the users.Therefore,monitoring the health status of pavement before irreversible damage occurs is essential for timely maintenance,which in turn ensures public transportation safety.Many pavement damages can be detected and analyzed by monitoring the structure dynamic responses and evaluating road surface conditions.Advanced technologies can be employed for the collection and analysis of such data,including various intrusive sensing techniques,image processing techniques,and machine learning methods.This review summarizes the state-ofthe-art of these three technologies in pavement engineering in recent years and suggests possible developments for future pavement monitoring and analysis based on these approaches.

An overview of thermoelectric films:Fabrication techniques,classification,and regulation methods

Thermoelectric materials have aroused widespread concern due to their unique ability to directly convert heat to electricity without any moving parts or noxious emissions.Taking advantages of two-dimensional structures of thermoelectric films,the potential applications of thermoelectric materials are diversified,particularly in microdevices.Well-controlled nanostructures in thermoelectric films are effective to optimize the electrical and thermal transport,which can significantly improve the performance of thermoelectric materials.In this paper,various physical and chemical approaches to fabricate thermoelectric films,including inorganic,organic,and inorganic–organic composites,are summarized,where more attentions are paid on the inorganic thermoelectric films for their excellent thermoelectric responses.Additionally,strategies for enhancing the performance of thermoelectric films are also discussed.

Methods and Techniques of Electricity Thieving in Pakistan

The situation of electricity in Pakistan has been alarming from the last ten years. The deficiency in electricity has not only obstructed the business activities but also affected the domestic consumers, educational institutes and hospitals. Usually electrical power companies are liable for electricity shortfall and power interruption. However, electricity end consumers are also equally responsible behind strange shortfall and unusual power interruption. Frequently, the consumers use the heavy electrical equipment in their homes including heaters, geysers, irons and water motors which causes the more electricity consumption, load shedding and huge amount of bills. For escaping the huge amount of electricity bill, the consumers commit the illegal and unethical connections. The illegal usage of electrical power failed the power companies to plan schedule load shedding accordingly and the other side the damaged electricity wires or Pole Mount Transformer increased faults due to overburdening, which directly affected on extend power interruption. In addition that, responsible teams of electrical power companies cannot reach instantly to repair faults and prevent the theft. Electricity thieving is social crime committed by the consumers or meter readers which causes the electricity strange shortfall within country. This paper presents the practical demonstration about the common energy theft methods and techniques done by electricity consumers within their home and residential building. In Pakistan EPC (electrical power companies) deploy the traditional electromechanical meters for electricity consumption measurements, however, these meters do not have any real time communication. Therefore there are many easy ways to manipulate the meter reading as well as internal structural of metering system.

Pulsar Candidate Classification Using a Computer Vision Method from a Combination of Convolution and Attention

Artificial intelligence methods are indispensable to identifying pulsars from large amounts of candidates.We develop a new pulsar identification system that utilizes the CoAtNet to score two-dimensional features of candidates,implements a multilayer perceptron to score one-dimensional features,and relies on logistic regression to judge the corresponding scores.In the data preprocessing stage,we perform two feature fusions separately,one for one-dimensional features and the other for two-dimensional features,which are used as inputs for the multilayer perceptron and the CoAtNet respectively.The newly developed system achieves 98.77%recall,1.07%false positive rate(FPR)and 98.85%accuracy in our GPPS test set.

A review of development methods and EOR technologies for carbonate reservoirs

Carbonate reservoirs worldwide are complex in structure,diverse in form,and highly heterogeneous.Based on these characteristics,the reservoir stimulation technologies and fluid flow characteristics of carbonate reservoirs are briefly described in this study.The development methods and EOR technologies of carbonate reservoirs are systematically summarized,the relevant mechanisms are analyzed,and the application status of oil fields is catalogued.The challenges in the development of carbonate reservoirs are discussed,and future research directions are explored.In the current development processes of carbonate reservoirs,water flooding and gas flooding remain the primary means but are often prone to channeling problems.Chemical flooding is an effective method of tertiary oil recovery,but the harsh formation conditions require high-performance chemical agents.The application of emerging technologies can enhance the oil recovery efficiency and environmental friendliness to a certain extent,which is welcome in hard-to-recover areas such as heavy oil reservoirs,but the economic cost is often high.In future research on EOR technologies,flow field control and flow channel plugging will be the potential directions of traditional development methods,and the application of nanoparticles will revolutionize the chemical EOR methods.On the basis of diversified reservoir stimulation,combined with a variety of modern data processing schemes,multichannel EOR technologies are being developed to realize the systematic,intelligent,and cost-effective development of carbonate reservoirs.

Screening and early diagnosis of osteoporosis through X-ray and ultrasound based techniques

Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinicallyavailable diagnostic methods are mainly based on the use of either X-rays or ultrasound(US). All X-ray based methods provide a measure of bone mineral density(BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry(DXA) is considered the current 'gold standard' for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations(e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound(QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this 'silent disease' and show up recent advances for its prevention and improved management through early diagnosis.

Integrating multisource RS data and GIS techniques to assist the evaluation of resource-environment carrying capacity in karst mountainous area

The karst mountainous area is an ecologically fragile region with prominent humanland contradictions.The resource-environment carrying capacity(RECC)of this region needs to be further clarified.The development of remote sensing(RS)and geographic information system(GIS)provides data sources and processing platform for RECC monitoring.This study analyzed and established the evaluation index system of RECC by considering particularity in the karst mountainous area of Southwest China;processed multisource RS data(Sentinel-2,Aster-DEM and Landsat-8)to extract the spatial distributions of nine key indexes by GIS techniques(information classification,overlay analysis and raster calculation);proposed the methods of index integration and fuzzy comprehensive evaluation of the RECC by GIS;and took a typical area,Guangnan County in Yunnan Province of China,as an experimental area to explore the effectiveness of the indexes and methods.The results showed that:(1)The important indexes affecting the RECC of karst mountainous area are water resources,tourism resources,position resources,geographical environment and soil erosion environment.(2)Data on cultivated land,construction land,minerals,transportation,water conservancy,ecosystem services,topography,soil erosion and rocky desertification can be obtained from RS data.GIS techniques integrate the information into the RECC results.The data extraction and processing methods are feasible on evaluating RECC.(3)The RECC of Guangnan County was in the mid-carrying level in 2018.The midcarrying and low-carrying levels were the main types,accounting for more than 80.00%of the total study area.The areas with high carrying capacity were mainly distributed in the northern regions of the northwest-southeast line of the county,and other areas have a low carrying capacity comparatively.The coordination between regional resource-environment status and socioeconomic development is the key to improve RECC.This study explores the evaluation index system of RECC in karst mountainous area and the application of multisource RS data and GIS techniques in the comprehensive evaluation.The methods can be applied in related fields to provide suggestions for data/information extraction and integration,and sustainable development.

Modified Masses and Parallaxes of Close Binary Systems: HD 39438

We present the detailed fundamental stellar parameters of the close visual binary system HD 39438 for the first time. We used Al-Wardat's method for analyzing binary and multiple stellar systems. The method implements Kurucz's plane parallel model atmospheres to construct synthetic spectral energy distributions(SEDs) for both components of the system. It then combines the results of the spectroscopic analysis with the photometric analysis and compares them with the observed ones to construct the best synthetic SED for the combined system. The analysis gives the precise fundamental parameters of the individual components of the system. Based on the positions of the components of HD 39438 on the H-R diagram, and evolutionary and isochrone tracks, we found that the system belongs to the main sequence stars with masses of 1.24 and 0.98 solar masses for the components A and B, respectively, and age of 1.995 Gyr for both components. The main result of HD 39438 is new dynamical parallax, which is estimated to be 16.689 ± 0.03 mas.

Harmonic Balance Methods:A Review and Recent Developments

The harmonic balance(HB)method is one of the most commonly used methods for solving periodic solutions of both weakly and strongly nonlinear dynamical systems.However,it is confined to low-order approximations due to complex symbolic operations.Many variants have been developed to improve the HB method,among which the time domain HB-like methods are regarded as crucial improvements because of their fast computation and simple derivation.So far,there are two problems remaining to be addressed.i)A dozen of different versions of HB-like methods,in frequency domain or time domain or in hybrid,have been developed;unfortunately,misclassification pervades among them due to the unclear borderlines of different methods.ii)The time domain HB-like methods suffer from non-physical solutions,which have been shown to be caused by aliasing(mixture of the high-order into the low-order harmonics).Although a series of dealiasing techniques have been developed over the past two decades,the mechanism of aliasing and the final solution to dealiasing are still not well known to the academic community.This paper aims to provide a comprehensive review of the development of HB-like methods and enunciate their principal differences.In particular,the time domain methods are emphasized with the famous aliasing phenomenon clearly addressed.

Extraction and Analysis of Coronal High-temperature Components Based on Outlier Detection

The extraction of high-temperature regions in active regions(ARs)is an important means to help understand the mechanism of coronal heating.The important observational means of high-temperature radiation in ARs is the main emission line of Fe XVⅢin the 94?of the Atmospheric Imaging Assembly.However,the diagnostic algorithms for Fe XVⅢ,including the differential emission measure(DEM)and linear diagnostics proposed by Del based on the DEM,have been greatly limited for a long time,and the results obtained are different from the predictions.In this paper,we use the outlier detection method to establish the nonlinear correlation between 94?and 171,193,211?based on the former researches by others.A neural network based on 171,193,211?is constructed to replace the low-temperature emission lines in the ARs of 94?.The predicted results are regarded as the low-temperature components of 94?,and then the predicted results are subtracted from 94?to obtain the outlier component of 94?,or Fe XVⅢ.Then,the outlier components obtained by neural network are compared with the Fe XVⅢobtained by DEM and Del's method,and a high similarity is found,which proves the reliability of neural network to obtain the high-temperature components of ARs,but there are still many differences.In order to analyze the differences between the Fe XVⅢobtained by the three methods,we subtract the Fe XVⅢobtained by the DEM and Del's method from the Fe XVⅢobtained by the neural network to obtain the residual value,and compare it with the results of Fe XIV in the temperature range of 6.1-6.45 MK.It is found that there is a great similarity,which also shows that the Fe XVⅢobtained by DEM and Del's method still has a large low-temperature component dominated by Fe XIV,and the Fe XVⅢobtained by neural network is relatively pure.

Direct Ion Beam Figuring Process and Rotational Measurement Method for Ultra-smooth Aspherical Surfaces of a 46.5 nm Telescope

This paper describes a fabrication process for the hyperboloidal concave mirror of a 46.5 nm telescope. The180 mm aperture hyperboloidal concave mirror and 70 mm aperture compensator are machined directly from chemical mechanical polishing of a spherical surface to a high-accuracy aspherical surface by ion beam figuring.The aspherical measurement method is the Dall null test. To minimize system errors in the measurement process,the rotational measurement method with six rotations is used in the null test. The results of the analysis for the ME(first solve the machined surface profile, then solve the system errors) and EM(first solve the system errors, then solve the machined surface profile) methods of calculation in the measurement are given. The ME method is a more accurate rotational test method, and the six rotations are appropriate for rotational measurements. After the figuring process, the hyperboloidal concave mirror surface profile reached 8.27 nm rms and the compensator surface profile is approximately 4 nm rms. The roughness of the hyperboloidal concave mirror is smooth to0.160 nm rms.

Solution of Stochastic Cubic and Quintic Nonlinear Diffusion Equation Using WHEP, Pickard and HPM Methods

In this paper, the cubic and quintic diffusion equation under stochastic non homogeneity is solved using Wiener- Hermite expansion and perturbation (WHEP) technique, Homotopy perturbation method (HPM) and Pickard approximation technique. The analytic solution of the linear case is obtained using Eigenfunction expansion .The Picard approximation method is used to introduce the first and second order approximate solution for the non linear case. The WHEP technique is also used to obtain approximate solution under different orders and different corrections. The Homotopy perturbation method (HPM) is also used to obtain some approximation orders for mean and variance. Using mathematica-5, the methods of solution are illustrated through figures, comparisons among different methods and some parametric studies.

A Unification of the Concepts of the Variational Iteration, Adomian Decomposition and Picard Iteration Methods;and a Local Variational Iteration Method

This paper compares the variational iteration method(VIM),the Adomian decomposition method(ADM)and the Picard iteration method(PIM)for solving a system of first o rder n onlinear o rdinary d ifferential e quations(ODEs).A unification of the concepts underlying these three methods is attempted by considering a very general iterative algorithm for VIM.It is found that all the three methods can be regarded as special cases of using a very general matrix of Lagrange multipliers in the iterative algorithm of VIM.The global variational iteration method is briefly reviewed,and further recast into a Local VIM,which is much more convenient and capable of predicting long term complex dynamic responses of nonlinear systems even if they are chaotic.

Detection of TiO and VO in the Atmosphere of WASP-121b and Evidence For its Temporal Variation

We report the transit observations of the ultra-hot Jupiter WASP-121b using the Goodman High Throughput Spectrograph at the 4 m ground-based Southern Astrophysical Research Telescope,covering the wavelength range502-900 nm.By dividing the target and reference star into 19 spectroscopic passbands and applying differential spectrophotometry,we derive spectroscopic transit light curves and fit them using a Gaussian process framework to determine transit depths for every passband.The obtained optical transmission spectrum shows a steep increased slope toward the blue wavelength,which seems to be too steep to be accounted for by Rayleigh scattering alone.We note that the transmission spectrum from this work and other works differ obviously from each other,which was pointed out previously by Wilson et al.as evidence for temporal atmospheric variation.We perform a free chemistry retrieval analysis on the optical transmission spectra from this work and the literature HST/WFC3 NIR spectrum.We determine TiO,VO and H_(2)O with abundances of-5.95_(-0.42)^(+0.47)dex,-6.72_(-1.79)^(+0.51)dex and-4.13_(-0.46)^(+0.63)dex,respectively.We compare the abundances of all three of these molecules derived from this work and previous works,and find that they are not consistent with each other,indicating the chemical compositions of the terminator region may change over long timescales.Future multi-epoch and high-precision transit observations are required to further confirm this phenomenon.We note that when combining the transmission spectra in the optical and in NIR in retrieval analysis,the abundances of V and VO,the NIR-to-optical offset and the cloud deck pressure may be coupled with each other.