Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Design and high-power testing of offline conditioning cavity for CiADS RFQ high-power coupler

To validate the design rationality of the power coupler for the RFQ cavity and minimize cavity contamination,we designed a low-loss offline conditioning cavity and conducted high-power testing.This offline cavity features two coupling ports and two tuners,operating at a frequency of 162.5 MHz with a tuning range of 3.2 MHz.Adjusting the installation angle of the coupling ring and the insertion depth of the tuner helps minimize cavity losses.We performed electromagnetic structural and multiphysics simulations,revealing a minimal theoretical power loss of 4.3%.However,when the cavity frequency varied by110 kHz,theoretical power losses increased to10%,necessitating constant tuner adjustments during conditioning.Multiphysics simulations indicated that increased cavity temperature did not affect frequency variation.Upon completion of the offline high-power conditioning platform,we measured the transmission performance,revealing a power loss of 6.3%,exceeding the theoretical calculation.Conditioning utilized efficient automatic range scanning and standing wave resonant methods.To fully condition the power coupler,a 15°phase difference between two standing wave points in the condition-ing system was necessary.Notably,the maximum continuous wave power surpassed 20 kW,exceeding the expected target.

Tailoring Classical Conditioning Behavior in TiO_(2) Nanowires:ZnO QDs-Based Optoelectronic Memristors for Neuromorphic Hardware

Neuromorphic hardware equipped with associative learn-ing capabilities presents fascinating applications in the next generation of artificial intelligence.However,research into synaptic devices exhibiting complex associative learning behaviors is still nascent.Here,an optoelec-tronic memristor based on Ag/TiO_(2) Nanowires:ZnO Quantum dots/FTO was proposed and constructed to emulate the biological associative learning behaviors.Effective implementation of synaptic behaviors,including long and short-term plasticity,and learning-forgetting-relearning behaviors,were achieved in the device through the application of light and electrical stimuli.Leveraging the optoelectronic co-modulated characteristics,a simulation of neuromorphic computing was conducted,resulting in a handwriting digit recognition accuracy of 88.9%.Furthermore,a 3×7 memristor array was constructed,confirming its application in artificial visual memory.Most importantly,complex biological associative learning behaviors were emulated by mapping the light and electrical stimuli into conditioned and unconditioned stimuli,respectively.After training through associative pairs,reflexes could be triggered solely using light stimuli.Comprehen-sively,under specific optoelectronic signal applications,the four features of classical conditioning,namely acquisition,extinction,recovery,and generalization,were elegantly emulated.This work provides an optoelectronic memristor with associative behavior capabilities,offering a pathway for advancing brain-machine interfaces,autonomous robots,and machine self-learning in the future.

Uncertainties of landslide susceptibility prediction: Influences of random errors in landslide conditioning factors and errors reduction by low pass filter method

In the existing landslide susceptibility prediction(LSP)models,the influences of random errors in landslide conditioning factors on LSP are not considered,instead the original conditioning factors are directly taken as the model inputs,which brings uncertainties to LSP results.This study aims to reveal the influence rules of the different proportional random errors in conditioning factors on the LSP un-certainties,and further explore a method which can effectively reduce the random errors in conditioning factors.The original conditioning factors are firstly used to construct original factors-based LSP models,and then different random errors of 5%,10%,15% and 20%are added to these original factors for con-structing relevant errors-based LSP models.Secondly,low-pass filter-based LSP models are constructed by eliminating the random errors using low-pass filter method.Thirdly,the Ruijin County of China with 370 landslides and 16 conditioning factors are used as study case.Three typical machine learning models,i.e.multilayer perceptron(MLP),support vector machine(SVM)and random forest(RF),are selected as LSP models.Finally,the LSP uncertainties are discussed and results show that:(1)The low-pass filter can effectively reduce the random errors in conditioning factors to decrease the LSP uncertainties.(2)With the proportions of random errors increasing from 5%to 20%,the LSP uncertainty increases continuously.(3)The original factors-based models are feasible for LSP in the absence of more accurate conditioning factors.(4)The influence degrees of two uncertainty issues,machine learning models and different proportions of random errors,on the LSP modeling are large and basically the same.(5)The Shapley values effectively explain the internal mechanism of machine learning model predicting landslide sus-ceptibility.In conclusion,greater proportion of random errors in conditioning factors results in higher LSP uncertainty,and low-pass filter can effectively reduce these random errors.

Operating Parameters of the District Heating Substation Cooperating With the Installation of Technological Air Conditioning With High Efficiency of Heat Recovery

The article analyses the problem of determining the operating parameters of the district heating substation cooperating with the air heating system in technological air conditioning systems equipped with heat exchangers with high efficiency of heat recovery.Attention was paid to the correct selection of heat exchangers for the heat output balance depending on the heat recovery protection algorithms against a drop in the temperature of the heat transfer surface below 0℃.Critical parameters were determined in Polish climatic conditions,at which the operation of the heat recovery exchanger in the air conditioning system is switched off or limited.It has been proven that the proper functioning of the district heating substation cooperating with the installation of air conditioning with high heat recovery efficiency requires the use of two heat exchangers with different characteristics,equipped with properly selected temperature control systems.The optimal model of cooperation between the technological air conditioning system and the heating substation was also indicated.

The potential mechanism and clinical application value of remote ischemic conditioning in stroke

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

Landslide susceptibility prediction using slope unit-based machine learning models considering the heterogeneity of conditioning factors

To perform landslide susceptibility prediction(LSP),it is important to select appropriate mapping unit and landslide-related conditioning factors.The efficient and automatic multi-scale segmentation(MSS)method proposed by the authors promotes the application of slope units.However,LSP modeling based on these slope units has not been performed.Moreover,the heterogeneity of conditioning factors in slope units is neglected,leading to incomplete input variables of LSP modeling.In this study,the slope units extracted by the MSS method are used to construct LSP modeling,and the heterogeneity of conditioning factors is represented by the internal variations of conditioning factors within slope unit using the descriptive statistics features of mean,standard deviation and range.Thus,slope units-based machine learning models considering internal variations of conditioning factors(variant slope-machine learning)are proposed.The Chongyi County is selected as the case study and is divided into 53,055 slope units.Fifteen original slope unit-based conditioning factors are expanded to 38 slope unit-based conditioning factors through considering their internal variations.Random forest(RF)and multi-layer perceptron(MLP)machine learning models are used to construct variant Slope-RF and Slope-MLP models.Meanwhile,the Slope-RF and Slope-MLP models without considering the internal variations of conditioning factors,and conventional grid units-based machine learning(Grid-RF and MLP)models are built for comparisons through the LSP performance assessments.Results show that the variant Slopemachine learning models have higher LSP performances than Slope-machine learning models;LSP results of variant Slope-machine learning models have stronger directivity and practical application than Grid-machine learning models.It is concluded that slope units extracted by MSS method can be appropriate for LSP modeling,and the heterogeneity of conditioning factors within slope units can more comprehensively reflect the relationships between conditioning factors and landslides.The research results have important reference significance for land use and landslide prevention.

Genesis of LCT Pegmatites during Early Paleozoic Orogeny of the North Qinling Orogenic Belt,China:Emplacement Conditions and Structural Control

The Guanpo pegmatite field in the North Qinling orogenic belt(NQB),China,hosts the most abundant LCT pegmatites.However,their emplacement conditions and structural control remain unexplored.In this contribution,we investigated it combining pegmatite orientation measurement with oxygen isotope geothermometry and fluid inclusion study.The orientations of type A1 pegmatites(P_(f)<σ_(2))are predominantly influenced by P-and T-fractures due to simple shearing in Shiziping dextral thrust shear zone during D_(2)deformation,whereas type A2 pegmatites(contemporaneous with D_(4))are governed by hydraulic fractures aligned with S_(0)and S_(0+1)stemming from fluid pressure(P_(f)<σ_(2)).Additionally,type B pegmatites(P_(f)≤σ_(2))exhibit orientations shaped by en echelon extensional fractures in local ductile shear zones(contemporaneous with D_(3)).The albite-quartz oxygen isotope geothermometry and microthermometric analysis of fluid inclusions in elbaites from the latest pegmatites(including types B and A2)suggest that the crystallization P-T for late magmatic and hydrothermal stages are 527.5-559.2℃,320℃,3.1-3.6 kbar and 2.0 kbar,respectively.Our observations along with previous studies suggest that the genesis of the LCT pegmatites was a long-term,multi-stage event during early Paleozoic orogeny(including the collision stage)of the NQB,and was facilitated by various local fractures.

Ambient-Condition Strategy for Production of Hollow Ga_(2)O_(3)@rGO Crystalline Nanostructures Toward Efficient Lithium Storage

Crystallineγ-Ga_(2)O_(3)@rGO core-shell nanostructures are synthesized in gram scale,which are accomplished by a facile sonochemical strategy under ambient condition.They are composed of uniformγ-Ga_(2)O_(3)nanospheres encapsulated by reduced graphene oxide(rGO)nanolayers,and their formation is mainly attributed to the existed opposite zeta potential between the Ga_(2)O_(3)and rGO.The as-constructed lithium-ion batteries(LIBs)based on as-fabricatedγ-Ga_(2)O_(3)@rGO nanostructures deliver an initial discharge capacity of 1000 mAh g^(-1)at 100 mA g^(-1)and reversible capacity of 600 mAh g^(-1)under 500 mA g^(-1)after 1000 cycles,respectively,which are remarkably higher than those of pristineγ-Ga_(2)O_(3)with a much reduced lifetime of 100 cycles and much lower capacity.Ex situ XRD and XPS analyses demonstrate that the reversible LIBs storage is dominant by a conversion reaction and alloying mechanism,where the discharged product of liquid metal Ga exhibits self-healing ability,thus preventing the destroy of electrodes.Additionally,the rGO shell could act robustly as conductive network of the electrode for significantly improved conductivity,endowing the efficient Li storage behaviors.This work might provide some insight on mass production of advanced electrode materials under mild condition for energy storage and conversion applications.

Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Localized Theoretical Analysis of Thermal Performance of Individually Finned Heat Pipe Heat Exchanger for Air Conditioning with Freon R404A as Working Fluid

This work contributes to the improvement of energy-saving in air conditioning systems. The objective is to apply the thermal efficiency of heat exchangers for localized determination of the thermal performance of heat exchangers with individually finned heat pipes. The fundamental parameters used for performance analysis were the number of fins per heat pipe, the number of heat pipes, the inlet temperatures, and the flow rates of hot and cold fluids. The heat exchanger under analysis uses Freon 404A as a working fluid in an air conditioning system for cooling in the Evaporator and energy recovery in the Condenser. The theoretical model is localized and applied individually to the Evaporator, Condenser, and heat exchanger regions. The results obtained through the simulation are compared with experimental results that use a global approach for the heat exchanger. The thermal quantities obtained through the theoretical model in the mentioned regions are air velocity, Nusselt number, thermal effectiveness, heat transfer rate, and outlet temperature. The comparisons made with global experimental results are in excellent agreement, demonstrating that the localized theoretical approach developed is consistent and can be used as a comprehensive analysis tool for heat exchangers using heat pipes.

Localized Theoretical Analysis of Thermal Performance of Individually Finned Heat Pipe Heat Exchanger for Air Conditioning with Freon R404A as Working Fluid

This work contributes to the improvement of energy-saving in air conditioning systems. The objective is to apply the thermal efficiency of heat exchangers for localized determination of the thermal performance of heat exchangers with individually finned heat pipes. The fundamental parameters used for performance analysis were the number of fins per heat pipe, the number of heat pipes, the inlet temperatures, and the flow rates of hot and cold fluids. The heat exchanger under analysis uses Freon 404A as a working fluid in an air conditioning system for cooling in the Evaporator and energy recovery in the Condenser. The theoretical model is localized and applied individually to the Evaporator, Condenser, and heat exchanger regions. The results obtained through the simulation are compared with experimental results that use a global approach for the heat exchanger. The thermal quantities obtained through the theoretical model in the mentioned regions are air velocity, Nusselt number, thermal effectiveness, heat transfer rate, and outlet temperature. The comparisons made with global experimental results are in excellent agreement, demonstrating that the localized theoretical approach developed is consistent and can be used as a comprehensive analysis tool for heat exchangers using heat pipes.

Conditional Kernel Covariance and Correlation

The conditional kernel correlation is proposed to measure the relationship between two random variables under covariates for multivariate data.Relying on the framework of reproducing kernel Hilbert spaces,we give the definitions of the conditional kernel covariance and conditional kernel correlation.We also provide their respective sample estimators and give the asymptotic properties,which help us construct a conditional independence test.According to the numerical results,the proposed test is more effective compared to the existing one under the considered scenarios.A real data is further analyzed to illustrate the efficacy of the proposed method.

Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition:Harnessing the power of nanotheranostics

Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.

Oscillation properties of eigenfunctions for Sturm-Liouville problems with interface conditions via Prufer transformation

A class of Sturm-Liouville problems with discontinuity is studied in this paper.The oscillation properties of eigenfunctions for Sturm-Liouville problems with interface conditions are obtained.The main method used in this paper is based on Prufer transformation,which is different from the classical ones.Moreover,we give two examples to verify our main results.

Role of outdoor trees on pedestrian wind and thermal conditions around a pre-education building for sustainable energy management

Finding sustainable energy resources is essential to face the increasing energy demand.Trees are an important part of ancient architecture but are becoming rare in urban areas.Trees can control and tune the pedestrian-level wind velocity and thermal condition.In this study,a numerical investigation is employed to assess the role of trees planted in the windward direction of the building complex on the thermal and pedestrian wind velocity conditions around/inside a pre-education building located in the center of the complex.Compared to the previous studies(which considered only outside buildings),this work considers the effects of trees on microclimate change both inside/outside buildings.Effects of different parameters including the leaf area density and number of trees,number of rows,far-field velocity magnitude,and thermal condition around the main building are assessed.The results show that the flow velocity in the spacing between the first-row buildings is reduced by 30%-40% when the one-row trees with 2 m height are planted 15 m farther than the buildings.Furthermore,two rows of trees are more effective in higher velocities and reduce the maximum velocity by about 50%.The investigation shows that trees also could reduce the temperature by about 1℃around the building.

Enhancing Erectile Function and Alleviating Andropause Symptoms: Clinical Efficacy of a Human Stem Cell Conditioned Medium Cream

Erectile dysfunction (ED) is increasingly prevalent in Japan, exceeding 30%, and increasing with age. Unhealthy lifestyle habits, obesity, insufficient exercise, and smoking have been implicated in its pathogenesis, along with endothelial dysfunction of the corpora cavernosa and impaired blood flow to the penis considered underlying factors. However, the current treatments are limited to Phosphodiesterase-5 (PDE5) inhibitors. ED is the primary symptom of andropathy. This study reports the clinical efficacy of human stem cell-conditioned medium cream for ED treatment. Ten men without underlying diseases suspected of andropause with ED (mean age 43.2 ± 4.4 y, Hb 15.2 ± 0.6 gm/dL, AST/ALT 30.2/37.9 ± 12.4/14.0, eGFR 82.7 ± 12.4 mL/min/1.73 m2) were targeted. The cream was applied twice daily to the genital and scrotal areas. The erectile hardness score (EHS), International Index of Erectile Function-5 (IIEF-5), and Aging Male Symptoms (AMS) scale were used to evaluate the participants before and 30 days after use, and the results were compared using paired t-tests. The post-use qualitative opinions were collected through interviews. Significant improvements were observed compared to baseline in the IIEF-5 (11.8 ± 4.6→17.2 ± 5.1, P < 0.001), and AMS (46.3 ± 6.7→37.6 ± 5.3, P < 0.001) scores post cream use. EHS did not show a statistically significant difference, but a trend towards improvement was observed. Qualitative feedback included increased morning erection, improved maintenance of erection during intercourse, and reduced post work fatigue. Human stem cell-conditioned medium contains endothelial growth factors that potentially contribute to the improvement of ED and andropause by enhancing corporal endothelial function. Future studies should include control groups to further investigate the efficacy of these treatments.

Multi-soliton solutions of coupled Lakshmanan-Porsezian-Daniel equations with variable coefficients under nonzero boundary conditions

This paper aims to investigate the multi-soliton solutions of the coupled Lakshmanan–Porsezian–Daniel equations with variable coefficients under nonzero boundary conditions.These equations are utilized to model the phenomenon of nonlinear waves propagating simultaneously in non-uniform optical fibers.By analyzing the Lax pair and the Riemann–Hilbert problem,we aim to provide a comprehensive understanding of the dynamics and interactions of solitons of this system.Furthermore,we study the impacts of group velocity dispersion or the fourth-order dispersion on soliton behaviors.Through appropriate parameter selections,we observe various nonlinear phenomena,including the disappearance of solitons after interaction and their transformation into breather-like solitons,as well as the propagation of breathers with variable periodicity and interactions between solitons with variable periodicities.

Effects of Initial and Boundary Conditions on Heavy Rainfall Simulation over the Yellow Sea and the Korean Peninsula:Comparison of ECMWF and NCEP Analysis Data Effects and Verification with Dropsonde Observation

This study evaluated the simulation performance of mesoscale convective system(MCS)-induced precipitation,focusing on three selected cases that originated from the Yellow Sea and propagated toward the Korean Peninsula.The evaluation was conducted for the European Centre for Medium-Range Weather Forecasts(ECMWF)and National Centers for Environmental Prediction(NCEP)analysis data,as well as the simulation result using them as initial and lateral boundary conditions for the Weather Research and Forecasting model.Particularly,temperature and humidity profiles from 3D dropsonde observations from the National Center for Meteorological Science of the Korea Meteorological Administration served as validation data.Results showed that the ECMWF analysis consistently had smaller errors compared to the NCEP analysis,which exhibited a cold and dry bias in the lower levels below 850 hPa.The model,in terms of the precipitation simulations,particularly for high-intensity precipitation over the Yellow Sea,demonstrated higher accuracy when applying ECMWF analysis data as the initial condition.This advantage also positively influenced the simulation of rainfall events on the Korean Peninsula by reasonably inducing convective-favorable thermodynamic features(i.e.,warm and humid lower-level atmosphere)over the Yellow Sea.In conclusion,this study provides specific information about two global analysis datasets and their impacts on MCS-induced heavy rainfall simulation by employing dropsonde observation data.Furthermore,it suggests the need to enhance the initial field for MCS-induced heavy rainfall simulation and the applicability of assimilating dropsonde data for this purpose in the future.

Research on shell-side heat and mass transfer with multi-component in LNG spiral-wound heat exchanger under sloshing conditions

The spiral-wound heat exchanger(SWHE) is the primary low-temperature heat exchanger for large-scale LNG plants due to its high-pressure resistance, compact structure, and high heat exchange efficiency. This paper studied the shell-side heat and mass transfer characteristics of vapor-liquid two-phase mixed refrigerants in an SWHE by combining a multi-component model in FLUENT software with a customized multicomponent mass transfer model. Besides, the mathematical model under the sloshing condition was obtained through mathematical derivation, and the corresponding UDF code was loaded into FLUENT as the momentum source term. The results under the sloshing conditions were compared with the relevant parameters under the steady-state condition. The shell-side heat and mass transfer characteristics of the SWHE were investigated by adjusting the component ratio and other working conditions. It was found that the sloshing conditions enhance the heat transfer performance and sometimes have insignificant effects. The sloshing condition is beneficial to reduce the flow resistance. The comprehensive performance of multi-component refrigerants has been improved and the improvement is more significant under sloshing conditions, considering both the heat transfer and pressure drop.These results will provide theoretical support for the research and design of multi-component heat and mass transfer enhancement of LNG SWHE under ocean sloshing conditions.