Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Analysis of deformation mechanisms in magnesium single crystals using a dedicated four-point bending tester

In this study,we explored the deformation mechanisms of Mg single crystals using a combination of scanning electron microscopy and electron backscattered diffraction in conjunction with a dedicated four-point bending tester.We prepared two single-crystal samples,oriented along the<1120>and<1010>directions,to assess the mechanisms of deformation when the initial basal slip was suppressed.In the<1120>sample,the primary{1012}twin(T1)was confirmed along the<1120>direction of the sample on the compression side with an increase in bending stress.In the<1010>sample,T1 and the secondary twin(T2)were confirmed to be along the<1120>direction,with an orientation of±60°with respect to the bending stress direction,and their direction matched with(0001)in T1 and T2.This result implies that crystallographically,the basal slip occurs readily.In addition,the<1010>sample showed the double twin in T1 on the compression side and the tertiary twin along the<1010>direction on the tension side.These results demonstrated that the maximum bending stress and displacement changed significantly under the bend loading because the deformation mechanisms were different for these single crystals.Therefore,the correlation between bending behavior and twin orientation was determined,which would be helpful for optimizing the bending properties of Mg-based materials.

The Impact of Nature, The Teaching and Learning of Elementary Lessons in Students 9-11 Years Old (Case Study: Shiraz Elementary Schools)

In today’s world some changes have been occurred in human lifestyle,these changes,along with the advantages,have led to a series of disadvantages including their disconnection with the nature.One of the most important areas to re-establish the relationship is the school.The presence of nature at schools,and holding some classes in nature,in addition to meeting the special needs of children causes their separation from those small and boring classes as well as their interest in courses.This study aimed to investigate the role of nature in children’s learning.For this purpose,third,fourth and fifth grade classes of 3 schools were held outside the school environment and in the nature in 5 courses.The study is a combinational research and field,indirect observation and library data collection methods were applied,where in the indirect observation,two types of questionnaires were prepared related to the students and teachers and were randomly distributed among 580 students and 50 elementary school teachers.Test reliability was assessed using Cronbach’s alpha and it was obtained to be 0.890.The results of this study indicate that the physical place as one of the factors in children’s learning has the maximum impact on teaching and learning of children.At the end of the study and by investigating the existing factors in the environment we understood that the expansion of the nature and natural light of it causes the students’interest in lessons in nature.

Quantification of Ride Comfort Using Musculoskeletal Mathematical Model Considering Vehicle Behavior

This research aims to quantify driver ride comfort due to changes in damper characteristics between comfort mode and sport mode,considering the vehicle’s inertial behavior.The comfort of riding in an automobile has been evaluated in recent years on the basis of a subjective sensory evaluation given by the driver.However,reflecting driving sensations in design work to improve ride comfort is abstract in nature and difficult to express theoretically.Therefore,we evaluated the human body’s effects while driving scientifically by quantifying the driver’s behavior while operating the steering wheel and the behavior of the automobile while in motion using physical quantities.To this end,we collected driver and vehicle data using amotion capture system and vehicle CAN and IMU sensors.We also constructed a three-dimensional musculoskeletal mathematical model to simulate driver movements and calculate the power and amount of energy per unit of time used for driving the joints and muscles of the human body.Here,we used comfort mode and sport mode to compare damper characteristics in terms of hardness.In comfort mode,damper characteristics are soft and steering stability is mild,but vibration from the road is not easily transmitted to the driver making for a lighter load on the driver.In sport mode,on the other hand,damper characteristics are hard and steering stability is comparatively better.Still,vibration from the road is easily transmitted to the driver,whichmakes it easy for a load to be placed on the driver.As a result of this comparison,it was found that a load was most likely to be applied to the driver’s neck.This result in relation to the neck joint can therefore be treated as an objective measure for quantifying ride comfort.

Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Impact of endoscopic screening on mortality reduction from gastric cancer

AIM:To investigate mortality reduction from gastric cancer based on the results of endoscopic screening.METHODS:The study population consisted of participants of gastric cancer screening by endoscopy,regular radiography,and photofluorography at Niigata city in 2005.The observed numbers of cumulative deaths from gastric cancers and other cancers were accumulated by linkage with the Niigata Prefectural Cancer Registry.The standardized mortality ratio(SMR)of gastric cancer and other cancer deaths in each screening group was calculated by applying the mortality rate of the reference population.RESULTS:Based on the results calculated from the mortality rate of the population of Niigata city,the SMRs of gastric cancer death were 0.43(95%CI:0.30-0.57)for the endoscopic screening group,0.68(95%CI:0.55-0.79)for the regular radiographic screening group,and 0.85(95%CI:0.71-0.94)for the photofluorography screening group.The mortality reduction from gastric cancer was higher in the endoscopic screening group than in the regular radiographic screening group despite the nearly equal mortality rates of all cancers except gastric cancer.CONCLUSION:The 57%mortality reduction from gastric cancer might indicate the effectiveness of endoscopic screening for gastric cancer.Further studies and prudent interpretation of results are needed.

Resistance Analysis of Unsymmetrical Trimaran Model with Outboard Sidehulls Configuration

The application of multi-hull ship or trimaran vessel as a mode of transports in both river and sea environments have grown rapidly in recent years.Trimaran vessels are currently of interest for many new high speed ship projects due to the high levels of hydrodynamic efficiency that can be achieved,compared to the mono-hull and catamaran hull forms.The purpose of this study is to identify the possible effects of using an unsymmetrical trimaran ship model with configuration（S/L） 0.1-0.3 and R/L=0.1-0.2.Unsymmetrical trimaran ship model with main dimensions： L=2000mm,B=200 mm and T=45 mm.Experimental methods（towing tank） were performed in the study using speed variations at Froude number 0.1-0.6.The ship model was pulled by an electric motor whose speed could be varied and adjusted.The ship model resistance was measured precisely by using a load cell transducer.The comparison of ship resistance for each configuration with mono-hull was shown on the graph as a function of the total resistance coefficient and Froude number.The test results found that the effective drag reduction could be achieved up to 17% at Fr=0.35 with configuration S/L=0.1.

ASSOCIATION OF PLASMA HOMOCYSTEINE LEVEL AND N^5, N^(10) -METHYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISM WITH CEREBRAL INFARCTION

Objective. To investigate the relationship of plasma homocysteine (Hcy) level to stroke and genetic factor to elevated plasma Hcy level.Methods. The plasma Hcy level was measured by capillary electrophoresis- ultraviolet detection and the gene polymorphism of N5, N10 - methylenetetrahydrofolate reductase (MTHFR) was studied with PCR - RFLP assay in 43 patients with cortical cerebral infarction and 42 healthy controls.Results. The plasma Hcy level of the patients ( 19. 3 + 6. 0 μ mol/L) was markedly higher than that of the controls (13.7 + 5.4 μ mol/L) ( t = 4. 16, P ＜ 0. 001). There are 3 genotypes, C/C, C/T and T/T, about base - variation of MTHFR gene at locus 677. The plasma Hcy level of the subjects with T/T genotype was higher than that of subjects with other genotypes. However, the frequencies of each genotype and allele were not significantly different between the patients and the controls.Conclusions. The elevated plasma Hcy level is a risk factor for atherothrombotic cerebral infarction, and is related to the C→T mutation at locus 677 of MTHFR gene.

Eutectic solidification mode of spheroidal graphite cast iron and graphitization

The shrinkage and chilling tendency of spheroidal graphite (abbreviated SG) cast iron is much greater than that of the flake graphite cast iron in spite of its higher amount of C and Si contents. Why? The main reason should be the difference in their graphitization during the eutectic solidification. In this paper, we discuss the difference in the solidification mechanism of both cast irons for solving these problems using unidirectional solidification and the cooling curves of the spheroidal graphite cast iron. The eutectic solidification rate of the SG cast iron is controlled by the diffusion of carbon through the austenite shell, and the final thickness is 1.4 times the radius of the SG, therefore, the reduction of the SG size, namely, the increase in the number, is the main solution of these problems.

Effect of Holding Time on the Microstructure and Mechanical Properties of Dual-Phase Steel during Intercritical Annealing

Continuous annealing simulation tests were conducted by using a continuous annealing thermomechanical simulator. Holding times of 5, 60, 180, and 480 seconds for an intercritical annealing temperature of 820℃ were adopted to investigate the evolution of the mierostructure and mechanical properties of ferrite-bainite dual-phase steel. The ferrite-bainite dual-phase steel was characterized by high strength and low yield ratio due to the presence of the constituents （polygonal ferrite, bainite, martensite and retained austenite） of the steel microstructure. Specimen 3 exhibits the highest value of A50 （7.67%） and a product of Rm × A50 （10453MPa%） after a 180s holding. This is likely attributed to the presence of a C-enriched retained anstenite in the microstructure. And the effect of martensite islands and carbide precipitate is thought to be able to contribute in strengthening the present steel. It is expected that equilibrium of anstenite fraction would be reached for reasonable intercritical holding period, regardless of the heating temperature. The results suggest that long increasing holding times may not be needed because the major phase of the microstructure does not change very significantly. It is favorable for industrial production of DP steels to shorten holding times. Key words： ferrite-bainite dual-phase steel; holding time; martensite islands; mechanical properties

Time-domain identification of dynamic properties of layered soil by using extended Kalman filter and recorded seismic data

A novel time-domain identification technique is developed for the seismic response analysis of soil-structure interaction.A two-degree-of-freedom (2DOF) model with eight lumped parameters is adopted to model the frequency- dependent behavior of soils.For layered soil,the equivalent eight parameters of the 2DOF model are identified by the extended Kalman filter (EKF) method using recorded seismic data.The polynomial approximations for derivation of state estimators are applied in the EKF procedure.A realistic identification example is given for the layered-soil of a building site in Anchorage,Alaska in the United States.Results of the example demonstrate the feasibility and practicality of the proposed identification technique.The 2DOF soil model and the identification technique can be used for nonlinear response analysis of soil-structure interaction in the time-domain for layered or complex soil conditions.The identified parameters can be stored in a database tor use in other similar soil conditions,lfa universal database that covers information related to most soil conditions is developed in the thture,engineers could conveniently perform time history analyses of soil-structural interaction.

Effects of urea-N fertilizer dosage supplemented with Ipil-Ipil tree litter on yield of rice and insect prevalence

The present study was undertaken to determine the effects of different levels of urea-N fertilizer in addition to ipil-ipil tree litter on yield of rice and insect prevalence. The field study was conducted at the Agroforestry Field Laboratory, Bangladesh Agricultural University, Mymensingh during July-December 2004. The treatments included 0, 90, 180, and 270 kg urea per hectare. All four treatments received five tons ipil-ipil tree litter per hectare. The experiment was laid out in a randomized complete block design （RCBD） with four replications. The results showed that the different treatments significantly influenced the yield and yield component viz. total tillers/hill, effective tillers/hill, filled grains and unfilled grains/panicle. The highest yield of 4.62 t·h^m-2 with an increase of 21.57% over the control was recorded in treatment 180 kg urea·h^m-2, which was statistically similar to treatment 90 kg urea·h^m-2. The prevalence of insects viz. green leafhopper, brown plant hopper, rice bugs, leaf folder and stem borers were mostly correlated with N-levels. The prevalence of insects in general gradu- ally increased with the increase of N. Therefore, this study suggests that the combined application of organic materials （tree litter of ipil-ipil） and N-fertilizer of 90 kg·h^m-2 may oroduce good yield while minimizine insect arevalence in the rice field.

Scattering of plane P waves by a semi-cylindrical hill: analytical solution

An analytical solution for scattering of plane P waves by a semi-cylindrical hill was derived by using the wave function expansion method, and convergence of the solution and accuracy of truncation were verified. The effect of incident frequency and incident angle on the surface motion of the hill was discussed, and it was shown that a hill greatly amplifies incident plane P waves, and maximum horizontal displacement amplitudes appear mostly at the inclined incidence of waves, which are located at the half-space; and maximum vertical displacement amplitudes emerge mostly at the vertical incidence of waves, which are situated at the hill.

Reduced order observer based identification of base isolated buildings

The objective of this study is to identify system parameters from the recorded response of base isolated buildings,such as USC hospital building,during the 1994 Northridge earthquake.Full state measurements are not available for identification.Additionally,the response is nonlinear due to the yielding of the lead-rubber bearings.Two new approaches are presented in this paper to solve the aforementioned problems.First,a reduced order observer is used to estimate the unmeasured states.Second,a least squares technique with time segments is developed to identify the piece-wise linear system properties.The observer is used to estimate the initial conditions needed for the time segmented identification.A series of equivalent linear system parameters are identified in different time segments.It is shown that the change in system parameters,such as frequencies and damping ratios,due to nonlinear behavior of the lead-rubber bearings,are reliably estimated using the presented technique.It is shown that the response was reduced due to yielding of the lead-rubber bearings and period lengthening.

Transient response of a beam on viscoelastic foundation under an impact load during nondestructive testing

Beam responses under an impact NDT load are studied using the Fourier and Laplace transforms. Numerical computation is performed for a parametric study of beam and load parameters. It is shown that under an impact load, the time duration for displacement to vanish is ten times longer than that for velocity and acceleration. The maximum response is achieved first in acceleration, followed by velocity, and finally displacement, all of which occur before the impact load is removed. At the moment that the impact load is removed from the beam, there is a discontinuity in the velocity and acceleration responses, but not in displacement response. The effect of K and ph on beam response is much less significant than that of EI and C, which have similar effect on beam response. As El increases, peak values of displacement, velocity and acceleration response decrease, The effect of K on beam response only becomes appreciable after the impact load is removed. While the peak of displacement remain almost unchanged large K values than for small K values. as K increases, the displacement response decays to zero faster for

Identification of acceleration pulses in near-fault ground motion using the EMD method

In this paper, response spectral characteristics of one-, two-, and three-lobe sinusoidal acceleration pulses are investigated, and some of their basic properties are derived. Furthermore, the empirical mode decomposition （EMD） method is utilized as an adaptive filter to decompose the near-fault pulse-like ground motions, which were recorded during the September 20, 1999, Chi-Chi earthquake. These ground motions contain distinct velocity pulses, and were decomposed into high-frequency （HF） and low-frequency （LF） components, from which the corresponding HF acceleration pulse （if existing） and LF acceleration pulse could be easily identified and detected. Finally, the identified acceleration pulses are modeled by simplified sinusoidal approximations, whose dynamic behaviors are compared to those of the original acceleration pulses as well as to those of the original HF and LF acceleration components in the context of elastic response spectra. It was demonstrated that it is just the acceleration pulses contained in the near-fault pulse-like ground motion that fundamentally dominate the special impulsive dynamic behaviors of such motion in an engineering sense. The motion thus has a greater potential to cause severe damage than the far-field ground motions, i.e. they impose high base shear demands on engineering structures as well as placing very high deformation demands on long-period structures.

Twin lintel belt in steel for seismic strengthening of brick masonry buildings

A single-room,single-storey full-scale brick masonry building with precast RC roofing system was tested thrice under displacement controlled lateral cyclic loading,to assess the effectiveness of the basic repair and seismic strengthening techniques.Initially,the virgin building specimen was loaded laterally to f^tilure.In the second stage,the damaged building was repaired by stitching across the cracks,and tested under the same lateral loading.In the third stage,the twice-damaged structure was repaired once more by stitching and strengthened by twin lintel belt in steel and vertical comer reinforcement, and re-tested.The building strengthened by twin lintel belt in steel showed about 28% higher strength under lateral loading than the virgin building.

In vitro scolicidal effect of Satureja khuzistanica(Jamzad)essential oil

Objective:To investigate the scolicidal effect of the Satureja khuzistanica(S.khusistanica) essential oil from aerial parts of this herbal plant.Methods:The essential oil was obtained by hydrodistillation method.Gas chromatography(GC) and gas chromatography mass spectrometry(GC-MS) were employed to determine the chemical composition of the essential oil.Protoscolices were collected aseptically from sheep livers containing hydatid cyst.Protoscolices were exposed to various concentrations of the oil(3,5 and 10 mg/mL) for 10,20,30,and 60 min.Viability of protoscolices was confirmed by 0.1%eosin staining.Results:A total of 19 compounds representing 97.6%of the total oil,were identified.Carvacrol(94.9%) was found to be the major essential oil constituent.Scolicidal activity of S.khuzistanica essential oil at concentration of 3 mg/mL was 28.58,32.71,37.20 and 42.02%,respectively.This essential oil at concentration of 5 mg/ mL killed 51.33,66.68,81.12,and 100%.of protoscolices after 10,20,30 and 60 min,respectively. One hundred scolicidal effect was observed with S.khuzistanica essenlial oil at the concentration of 10 mg/mL after 10 min(comparing with 7.19%for control group).Conclusions:The essenlial oil of S.khuzistanica is rich in carvacrol and may be used as a natural scolicidal agent.

Isothermal and athermal martensitic transformations of ceria cerla doped zilrconian

Martensitic transformation behavior was studied for zirconia containing 4%～10% CeO2 (in mole fraction) by using a dilatometric method. The Ms (Martensite start temperature) decreased near linearly with increasing CeO2. Different transformation modes were observed depending on the composition and cooling rate. ZrO2 containing 6% CeO2 showed isothermal transformation behavior, whereas ZrO2 containing 9% and 10% CeO2 showed athermal transformation behavior. However, ZrO2 containing 8% CeO2 showed either isothermal or athermal transformations behavior depending on the cooling rate. A TTT (Time-Temperature-Transformation) diagram was proposed for ZrO2 containing 8% CeO2.

Optimization of a High Speed Spinning Disk Spindle System for Minimum RRO,NRRO,and Lightweight by Using G.A.

Law level of RRO(Repeatable Run Out),NRRO(Non Repe at able Run Out),and lightweight construction are a major trend in the high-speed HDD(Hard Disk Drive)sytem to reduce track misregestration and to achieve high track density,which lead to succeed in the market.However,it is not easy to r educe RRO,NRRO,and the weight of the spinning disk spindle system efficiently because lightweight construction and or bearing stiffness changes often yields a decrease in the static and dynamic stiffness of the system,and consequently hi gh vibrations may be generated as a results.Therefore,it is of importance to e valuate in advance the accurate dynamic behavior of the high speed spinning disk spindle system of a HDD sysem.This study introduces an optimum design of the high speed spinning disk spindle system of a HDD for minimum RRO,NRRO,and lightweight construction using a gene tic algorithm.The spinning disk,hub,and bearing components of a HDD system ar e modelled as appropriate finite elements respectively and their equations of mo tion are derived to construct the system equations of the whole spinning disk sp indle system of the HDD system.The RRO and NRRO responses of the spinning disk,due to exciting forces arised from ball bearing faults and rotating unbalance,are analyzed.In the design optimation,the hub thickness,the disk thickness,bearing positio ns(or bearing span)and bearing stiffness were set as design variables.The uni que objective function is obtained by multiplying an appropriate weighting facto r by multi-objective functions,such as RRO,NRRO,and the total weight of HDD the system.The constraints are maximum RRO limit,maximum weight linit,and the critical speed limit of the HDD spindle system.Results show that the RRO,NRRO,and weight are reduced by 6%,66.7%and 28%r espectively compared with the initial design of the HDD system.Therefore,thi s present study can be used for an optimum design of the spinning disk spindle s ystem of a HDD for lightweight construction and low vibrations.