Glia-to-neuron reprogramming to the rescue?

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

Neurocircuit regeneration by extracellular matrix reprogramming

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

Post-processing Free Quantum Random Number Generator Based on Avalanche Photodiode Array

Quantum random number generators adopting single negligible dead time of avalanche photodiodes （APDs） photon detection have been restricted due to the non- We propose a new approach based on an APD array to improve the generation rate of random numbers significantly. This method compares the detectors＇ responses to consecutive optical pulses and generates the random sequence. We implement a demonstration experiment to show its simplicity, compactness and scalability. The generated numbers are proved to be unbiased, post-processing free, ready to use, and their randomness is verified by using the national institute of standard technology statistical test suite. The random bit generation efficiency is as high as 32.8% and the potential generation rate adopting the 32× 32 APD array is up to tens of Gbits/s.

Pre-processing and post-processing method for geostress simulation using seismic interpretation results

In order to carry out numerical simulation using geologic structural data obtained from Landmark(seismic interpretation system), underground geological structures are abstracted into mechanical models which can reflect actual situations and facilitate their computation and analyses.Given the importance of model building, further processing methods about traditional seismic interpretation results from Landmark should be studied and the processed result can then be directly used in numerical simulation computations.Through this data conversion procedure, Landmark and FLAC(the international general stress software) are seamlessly connected.Thus, the format conversion between the two systems and the pre-and post-processing in simulation computation is realized.A practical application indicates that this method has many advantages such as simple operation, high accuracy of the element subdivision and high speed, which may definitely satisfy the actual needs of floor grid cutting.

Development of a Post-Processing Automation Procedure for the GPS-Based Travel Time Data Collection Technique

The travel time data collection method is used to assist the congestion management. The use of traditional sensors (e.g. inductive loops, AVI sensors) or more recent Bluetooth sensors installed on major roads for collecting data is not sufficient because of their limited coverage and expensive costs for installation and maintenance. Application of the Global Positioning Systems (GPS) in travel time and delay data collections is proven to be efficient in terms of accuracy, level of details for the data and required data collection of man-power. While data collection automation is improved by the GPS technique, human errors can easily find their way through the post-processing phase, and therefore data post-processing remains a challenge especially in case of big projects with high amount of data. This paper introduces a stand-alone post-processing tool called GPS Calculator, which provides an easy-to-use environment to carry out data post-processing. This is a Visual Basic application that processes the data files obtained in the field and integrates them into Geographic Information Systems (GIS) for analysis and representation. The results show that this tool obtains similar results to the currently used data post-processing method, reduces the post-processing effort, and also eliminates the need for the second person during the data collection.

A study on fast post-processing massive data of casting numerical simulation on personal computers

When castings become complicated and the demands for precision of numerical simulation become higher,the numerical data of casting numerical simulation become more massive.On a general personal computer,these massive numerical data may probably exceed the capacity of available memory,resulting in failure of rendering.Based on the out-of-core technique,this paper proposes a method to effectively utilize external storage and reduce memory usage dramatically,so as to solve the problem of insufficient memory for massive data rendering on general personal computers.Based on this method,a new postprocessor is developed.It is capable to illustrate filling and solidification processes of casting,as well as thermal stess.The new post-processor also provides fast interaction to simulation results.Theoretical analysis as well as several practical examples prove that the memory usage and loading time of the post-processor are independent of the size of the relevant files,but the proportion of the number of cells on surface.Meanwhile,the speed of rendering and fetching of value from the mouse is appreciable,and the demands of real-time and interaction are satisfied.

A method of line spectrum extraction based on target radiated spectrum feature and its post-processing

To improve the ability of detecting underwater targets under strong wideband interference environment,an efficient method of line spectrum extraction is proposed,which fully utilizes the feature of the target spectrum that the high intense and stable line spectrum is superimposed on the wide continuous spectrum.This method modifies the traditional beam forming algorithm by calculating and fusing the beam forming results at multi-frequency band and multi-azimuth interval,showing an excellent way to extract the line spectrum when the interference and the target are not in the same azimuth interval simultaneously.Statistical efficiency of the estimated azimuth variance and corresponding power of the line spectrum band depends on the line spectra ratio(LSR)of the line spectrum.The change laws of the output signal to noise ratio(SNR)with the LSR,the input SNR,the integration time and the filtering bandwidth of different algorithms bring the selection principle of the critical LSR.As the basis,the detection gain of wideband energy integration and the narrowband line spectrum algorithm are theoretically analyzed.The simulation detection gain demonstrates a good match with the theoretical model.The application conditions of all methods are verified by the receiver operating characteristic(ROC)curve and experimental data from Qiandao Lake.In fact,combining the two methods for target detection reduces the missed detection rate.The proposed post-processing method in2-dimension with the Kalman filter in the time dimension and the background equalization algorithm in the azimuth dimension makes use of the strong correlation between adjacent frames,could further remove background fluctuation and improve the display effect.

Improved Sinusoid Analysis and Post-Processing in Parametric Audio Coding

This paper proposed improvements to the low bit rate parametric audio coder with sinusoid model as its kernel. Firstly, we propose a new method to effectively order and select the perceptually most important sinusoids. The sinusoid which contributes most to the reduction of overall NMR is chosen. Combined with our improved parametric psychoacoustic model and advanced peak riddling techniques, the number of sinusoids required can be greatly reduced and the coding efficiency can be greatly enhanced. A lightweight version is also given to reduce the amount of computation with only little sacrifice of performance. Secondly, we propose two enhancement techniques for sinusoid synthesis: bandwidth enhancement and line enhancement. With little overhead, the effective bandwidth can be extended one more octave; the timbre tends to sound much brighter, thicker and more beautiful.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma

BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.

A Post-Processing Algorithm for Boosting Contrast of MRI Images

Low contrast of Magnetic Resonance(MR)images limits the visibility of subtle structures and adversely affects the outcome of both subjective and automated diagnosis.State-of-the-art contrast boosting techniques intolerably alter inherent features of MR images.Drastic changes in brightness features,induced by post-processing are not appreciated in medical imaging as the grey level values have certain diagnostic meanings.To overcome these issues this paper proposes an algorithm that enhance the contrast of MR images while preserving the underlying features as well.This method termed as Power-law and Logarithmic Modification-based Histogram Equalization(PLMHE)partitions the histogram of the image into two sub histograms after a power-law transformation and a log compression.After a modification intended for improving the dispersion of the sub-histograms and subsequent normalization,cumulative histograms are computed.Enhanced grey level values are computed from the resultant cumulative histograms.The performance of the PLMHE algorithm is comparedwith traditional histogram equalization based algorithms and it has been observed from the results that PLMHE can boost the image contrast without causing dynamic range compression,a significant change in mean brightness,and contrast-overshoot.

Hybrid Post-Processing Procedure for Displacement-Based Plane Elements

In the analysis of high-rise building, traditional displacement-based plane elements are often used to get the in-plane internal forces of the shear walls by stress integration. Limited by the singular problem produced by wall holes and the loss of precision induced by using differential method to derive strains, the displacement-based elements cannot always present accuracy enough for design. In this paper, the hybrid post-processing procedure based on the Hellinger-Reissner variational principle is used for improving the stress precision of two quadrilateral plane elements. In order to find the best stress field, three different forms are assumed for the displacement-based plane elements and with drilling DOF. Numerical results show that by using the proposed method, the accuracy of stress solutions of these two displacement-based plane elements can be improved.

Uncertainty quantification of inverse analysis for geomaterials using probabilistic programming

Uncertainty is an essentially challenging for safe construction and long-term stability of geotechnical engineering.The inverse analysis is commonly utilized to determine the physico-mechanical parameters.However,conventional inverse analysis cannot deal with uncertainty in geotechnical and geological systems.In this study,a framework was developed to evaluate and quantify uncertainty in inverse analysis based on the reduced-order model(ROM)and probabilistic programming.The ROM was utilized to capture the mechanical and deformation properties of surrounding rock mass in geomechanical problems.Probabilistic programming was employed to evaluate uncertainty during construction in geotechnical engineering.A circular tunnel was then used to illustrate the proposed framework using analytical and numerical solution.The results show that the geomechanical parameters and associated uncertainty can be properly obtained and the proposed framework can capture the mechanical behaviors under uncertainty.Then,a slope case was employed to demonstrate the performance of the developed framework.The results prove that the proposed framework provides a scientific,feasible,and effective tool to characterize the properties and physical mechanism of geomaterials under uncertainty in geotechnical engineering problems.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Recent Progress in Reinforcement Learning and Adaptive Dynamic Programming for Advanced Control Applications

Reinforcement learning(RL) has roots in dynamic programming and it is called adaptive/approximate dynamic programming(ADP) within the control community. This paper reviews recent developments in ADP along with RL and its applications to various advanced control fields. First, the background of the development of ADP is described, emphasizing the significance of regulation and tracking control problems. Some effective offline and online algorithms for ADP/adaptive critic control are displayed, where the main results towards discrete-time systems and continuous-time systems are surveyed, respectively.Then, the research progress on adaptive critic control based on the event-triggered framework and under uncertain environment is discussed, respectively, where event-based design, robust stabilization, and game design are reviewed. Moreover, the extensions of ADP for addressing control problems under complex environment attract enormous attention. The ADP architecture is revisited under the perspective of data-driven and RL frameworks,showing how they promote ADP formulation significantly.Finally, several typical control applications with respect to RL and ADP are summarized, particularly in the fields of wastewater treatment processes and power systems, followed by some general prospects for future research. Overall, the comprehensive survey on ADP and RL for advanced control applications has d emonstrated its remarkable potential within the artificial intelligence era. In addition, it also plays a vital role in promoting environmental protection and industrial intelligence.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Adaptive Optimal Discrete-Time Output-Feedback Using an Internal Model Principle and Adaptive Dynamic Programming

In order to address the output feedback issue for linear discrete-time systems, this work suggests a brand-new adaptive dynamic programming(ADP) technique based on the internal model principle(IMP). The proposed method, termed as IMP-ADP, does not require complete state feedback-merely the measurement of input and output data. More specifically, based on the IMP, the output control problem can first be converted into a stabilization problem. We then design an observer to reproduce the full state of the system by measuring the inputs and outputs. Moreover, this technique includes both a policy iteration algorithm and a value iteration algorithm to determine the optimal feedback gain without using a dynamic system model. It is important that with this concept one does not need to solve the regulator equation. Finally, this control method was tested on an inverter system of grid-connected LCLs to demonstrate that the proposed method provides the desired performance in terms of both tracking and disturbance rejection.

Recovery after ischemic stroke:Effects of FuekFone home-based program on upper limb and cognitive function

Objectives:This study aimed to explore the effects of the“FuekFone(F.F.)home-based program”on the upper limb and cognitive function of ischemic stroke patients after discharge.Methods:A single group pre-and post-test design was conducted.A total of 40 patients with recovery after ischemic stroke were recruited from two university hospitals in Thailand.The study was conducted between June 2022 and January 2023.Participants underwent a six-week“F.F.home-based program,”which combined an upper limb and cognitive function rehabilitation device with Android games,including stationary barrel,adventure walk,adventure stroll,sliding barrel,sauce squeeze,and cut objects.Each game has different difficulty levels.Patients can perform corresponding exercises through the games according to their conditions under the guidance of medical staff.The patients played for 24 min per time,4 min each game,three days a week.The second week,let the patients play games for 30 min per time,5 min each game,3 days a week.Then,in the 3e6 weeks,let the patients play games for 1 h per time,10 min each game,5 days a week.At the pre-and post-intervention,the Thai version of the National Institutes of Health Stroke Scale(NIHSS),the Motor Assessment Scale,and the Montreal Cognitive Assessment(MoCA score)were administered to patients at discharge and at 2,4,and 6 weeksafter discharge,and the results were compared.Results:All participants completed this program.Participants had statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 2,4,and 6 weeks after discharge(P<0.001).In the comparison of upper limb function and cognitive function at each of the study times,we found statistically improved upper limb function(upper arm function score,hand movements score,advanced hand activities score,total Motor Assessment Scale score)and MoCA score at 4,and 6 weeks after discharge when compared to after discharge and 2 weeks after discharge,respectively(P<0.05).Conclusions:Continuing care of patients post-stroke after discharge from hospital,such as F.F.homebased program should be applied at home to enhance upper limb and cognitive function.

In vivo astrocyte reprogramming following spinal cord injury

Harmful and helpful roles of astrocytes in spinal cord injury(SCI):SCI induce gradable sensory,motor and autonomic impairments that correlate with the lesion severity and the rostro-caudal location of the injury site.The absence of spontaneous axonal regeneration after injury results from neuron-intrinsic and neuron-extrinsic parameters.Indeed,not only adult neurons display limited capability to regrow axons but also the injury environment contains inhibitors to axonal regeneration and a lack of growth-promoting factors.Amongst other cell populations that respond to the lesion,reactive astrocytes were first considered as only detrimental to spontaneous axonal regeneration.Indeed,astrocytes.

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone formation.As novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets.This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation.Osteoclasts were differentiated from CD14+monocytes from eight female donors.RNA sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across donors.These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs.Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks.The donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature osteoclasts.The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and activity.The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts.In conclusion,we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity.These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.

Metabolic reprogramming in skeletal cell differentiation

The human skeleton is a multifunctional organ made up of multiple cell types working in concert to maintain bone and mineral homeostasis and to perform critical mechanical and endocrine functions.From the beginning steps of chondrogenesis that prefigures most of the skeleton,to the rapid bone accrual during skeletal growth,followed by bone remodeling of the mature skeleton,cell differentiation is integral to skeletal health.