Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Extraction of Echo Characteristics of Underwater Target Based on Cepstrum Method

The analysis and characteristic extraction of target echo characteristics are important in underwater target detection and recognition. Rigid acoustic scattering components are generally used as major echo contributors with relatively stable characteristic information. Previous studies focus on echo characteristics from a single angle, thereby limiting the amount of extracted characteristic information. This paper aims to establish a full-angle rigid echo components model and overcome the difficulty of the extraction of time delay characteristics of narrow-band acoustic scattering echoes. On the basis of the analysis of the target echo highlight model, the echo characteristics of rigid acoustic scattering components are extracted in the cepstrum domain, and a wavelet process is proposed to enhance the effect of time delay estimation. Experimental data indicate that the extracted time delay characteristics accord with the rigid echo characteristics of underwater target, thereby validating the effectiveness of the cepstrum method.

Classification of Underwater Target Echoes Based on Auditory Perception Characteristics

In underwater target detection, the bottom reverberation has some of the same properties as the target echo, which has a great impact on the performance. It is essential to study the difference between target echo and reverberation. In this paper, based on the unique advantage of human listening ability on objects distinction, the Gammatone filter is taken as the auditory model. In addition, time-frequency perception features and auditory spectral features are extracted for active sonar target echo and bottom reverberation separation. The features of the experimental data have good concentration characteristics in the same class and have a large amount of differences between different classes, which shows that this method can effectively distinguish between the target echo and reverberation.

The Echo Modelling and Simulation of the Semi-Active Radar Seeker against a Sea Skimming Target

This paper has proposed a new modelling and simulating technique for the echo of the semi-active radar seeker against the sea skimming target. The echo modelling is based on the electromagnetic scattering mechanisms. A modified Four-path model based on the radar detection scene is used to describe the multipath scattering between the target and rough sea surface. A Facet-based Small Slope Approximation (FBSSA) method is employed to calculate the scattering from the sea surface. The Physical Optics (PO) and the Equivalent Edge Current (EEC) Method is used to calculate the target scattering. In the echo simulations. The results present the original echo and the echo processed by the signal processing procedures, where the clutter and multipath effect can be observed.

Ex situ echo sounder target strengths of ice krill Euphausia crystallorophias

Ice krill is the keystone species in the neritic ecosystem in the Southern Ocean, where it replaces the more oceanic Antarctic krill. It is essential to understand the variation of target strength （TS in dB re l m^2） with the different body size to accurately estimate ice krill stocks. However, there is comparatively little knowledge of the acoustic backscatter of ice krill. The TS of individual, formalin-preserved, tethered ice krill was measured in a freshwater test tank at 38, 120, and 200 kHz with a calibrated split-beam echo sounder system. Mean TS was obtained from 21 individual ice krill with a broad range of body lengths （L： 13-36 iron）. The length （L, mm） to wet weight （W; mg） relationship for ice krill was 11/=0.001 21g^103~L35s （R2=0.96）. The mean TS-to-length relationship were TS38kHz=-177.4＋57log10（L）, （R^2=0.86）; TS120kHz= -129.9＋31.561ogf0（L）, （R2=0.87）; and TS200kHz=-117.6＋24.661ogre（L）, （R2=0.84）. Empirical estimates of the relationship between the TS and body length of ice krill were established at 38, 120, and 200 kHz and compared with predictions obtained from both the linear regression model of Greene et al. （1991） and the Stochastic Distorted Wave Born Approximation （SDWBA） model. This result might be applied to improve acoustic detection and density estimation of ice krill in the Southern Ocean. Further comparative studies are needed with in situ target strength including various body lengths of ice krill.

To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided quick identification with the help of SGTF phenomenon within 5 hours of duration. This strategy helps scientists and health policymakers for the quick isolation and identification of clusters. That ultimately results in a decreased transmission of pathogen among the community.

Impacts of space-time-frequency synchronization errors onwide-band target echo characteristics of bistatic/multistatic radar

Bistatic/multistatic radar has great potential advantages over its monostatic counterpart. However, the separation of a transmitter and a receiver leads to difficulties in locating the target position accurately and guaranteeing space-timefrequency synchronization of the transmitter and the receiver.The error model of space-time-frequency synchronization in a motion platform of bistatic/multistatic radar is studied. The relationship between the space synchronization error and the transmitter platform position, receiver platform position, moving state, and beam pointing error, is analyzed. The effect of space synchronization error on target echo power is studied. The target scattering characteristics are restructured by many separate scattering centers of the target in high frequency regions. Based on the scattering centers model of the radar target, this radar target echo model and the simulation method are discussed. The algorithm of bistatic/multistatic radar target echo accurately reflects the scattering characteristics of the radar target, pulse modulation speciality of radar transmitting signals, and spacetime-frequency synchronization error characteristics between the transmitter station and the receiver station. The simulation of bistatic radar is completed in computer, and the results of the simulation validate the feasibility of the method.

Is 26S proteasome non-ATPase regulatory subunit 6 a potential molecular target for intrahepatic cholangiocarcinoma?

In this editorial we comment on the article by Tang et al published in the recent issue of World Journal of Hepatology.Drug therapy of intrahepatic cholangiocarcinoma(iCCA)poses an enormous challenge since only a small proportion of patients demonstrate beneficial responses to therapeutic agents.Thus,there has been a sustained search for novel molecular targets for iCCA.The study by Tang et al evaluated the role of 26S proteasome non-ATPase regulatory subunit 6(PSMD6),a 19S regulatory subunit of the proteasome,in human iCCA cells and specimens.The authors employed clustered regularly interspaced short palindromic repeat(CRISPR)knockout screening technology integrated with the computational CERES algorithm,and analyzed the human protein atlas(THPA)database and tissue microarrays.The results show that PSMD6 is a gene essential for the proliferation of 17 iCCA cell lines,and PSMD6 protein was overexpressed in iCCA tissues without a significant correlation with the clinicopathological parameters.The authors conclude that PSMD6 may play a promoting role in iCCA.The major limitations and defects of this study are the lack of detailed information of CRISPR knockout screening,in vivo experiments,and a discussion of plausible mechanistic cues,which,therefore,dampen the significance of the results.Further studies are required to verify PSMD6 as a molecular target for developing novel therapeutics for iCCA.In addition,the editorial article summarizes the latest advances in molecular targeted drugs and recently emerging immunotherapy in the clinical management of iCCA,development of proteasome inhibitors for cancer therapy,and advantages of CRISPR screening technology,computational methods,and THPA database as experimental tools for fighting cancer.We hope that these comments may provide some clues for those engaged in the field of basic and clinical research into iCCA.

Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

Analysis of echo signal modulation characteristic parameters on aerial and space targets

Based on the scattering characteristic,the comparison of RCS(radar cross-section)at different positions of a target in the same direction of incidence can be obtained first by extruding or deleting part of the entity.A simulation method of aerial&space targets echo characteristics(A&STEC)is proposed that is universal to aerial and space targets.We utilize a fixed-wing UAV(unmanned aerial vehicle)and typical missiles in simulation.The echo signal modulation characteristic parameters are calculated theoretically by the atmospheric attenuation model,the finite element method and a MUMPS solver.The verification simulations show that this method can analyze the influence of the target shape,incident direction,detection position and detection frequency on echo waveform,intensity and energy distribution.The results show that the profile of echo waveform can invert the general shape of the target.The relationship between time and intensity can determine whether the target is moving towards or away from the detector in addition.These conclusions can provide a reference for the ballistic missile target tracking and the defense against UVA intrusion in theory.

事件驱动的B/S系统开发框架Echo研究

传统的B/S开发框架受HTTP协议及浏览器功能的限制,开发的程序在界面、功能上存在着一定的不足。同时,混用HTML、JavaScript等语言增大了开发的难度,并且使得程序的性能、可移植性大大下降。文章介绍了新出现的一种纯事件驱动和面向对象的B/S开发框Echo的技术和应用,给出了解决这一系列问题的一个思路:利用Echo框架,可以完全使用单一的面相对象的Java语言,开发出事件驱动的具有良好可维护性和可移植的B/S系统。

Simulink/RTW下xPC Target的S函数驱动模块开发

MathWorks公司提供了一个基于RTW的xPC Target。使用xPC Target,用户可以将一台PC机转变为一个实时系统,以实现对外部I/O设备的实时控制。xPC Target为外部I/O设备提供了部分驱动,但也支持其它I/O设备的连接,这需要用户编写驱动模块来实现对设备的接入。以研祥PCL818HD为例,介绍了驱动模块的实现过程。

D-S证据理论在空中目标识别中的应用现状与展望

D-S证据理论作为一种多源信息融合工具,在空中目标识别领域中得到了广泛应用。对D-S证据理论进行了概述;简要梳理了D-S证据理论在空中目标识别领域中的发展脉络,并提出应用中需要解决的三类关键问题;围绕上述问题,重点对该领域中的BPA获取、证据冲突度量、证据融合的应用现状进行综述;最后,基于空域控制视角,对D-S证据理论在该领域中的应用进行了展望。研究可为空中目标识别领域的理论发展和工程应用提供参考。

MicroRNAs in Parkinson's disease and emerging therapeutic targets

Parkinson＇s disease（PD） is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons. Oxidative stress is also recognized as one of the main causes of PD, and excessive reactive oxygen species（ROS） and reactive nitrogen species can lead to dopaminergic neuron vulnerability and eventual death. Micro RNAs control a range of physiological and pathological functions, and may serve as potential targets for intervention against PD to mitigate damage to the brain. Several studies have demonstrated that micro RNAs can regulate oxidative stress and prevent ROS-mediated damage to dopaminergic neurons, suggesting that specific micro RNAs may be putative targets for novel therapeutic strategies in PD. Recent human and animal studies have identified a large number of dysregulated micro RNAs in PD brain tissue samples, many of which were downregulated. The dysregulated micro RNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13 B, LTA, SLC5 A3, PSMB2, GSR, GBA, LAMP-2 A, HSC. Apart from one study, none of the studies reviewed had used agomirs or antagomirs to reverse the levels of downregulated or upregulated micro RNAs, respectively, in mouse models of PD or with isolated human or mouse dopaminergic cells. Further large-scale studies of brain tissue samples collected with short postmortem interval from human PD patients are warranted to provide more information on the micro RNA profiles in different brain regions and to test for gender differences.

An analysis of China's CO_2 emission peaking target and pathways

China has set the goal for its CO2 emissions to peak around 2030, which is not only a strategic decision coordinating domestic sustainable development and global climate change mitigation but also an overarching target and a key point of action for China＇s resource conservation, environmental protection, shift in economic development patterns, and CO2 emission reduction to avoid climate change. The development stage where China maps out the CO2 emission peak target is earlier than that of the developed countries. It is a necessity that the non-fossil energy supplies be able to meet all the increased energy demand for achieving CO2 emission peaking. Given that China＇s potential GDP annual increasing rate will be more than 4%, and China＇s total energy demand will continue to increase by approximately 1.0%--1.5% annually around 2030, new and renewable energies will need to increase by 6%-8% annually to meet the desired CO2 emission peak. The share of new and renewable energies in China＇s total primary energy supply will be approximately 20% by 2030. At that time, the energy consumption elasticity will decrease to around 0.3, and the annual decrease in the rate of CO2 intensity will also be higher than 4% to ensure the sustained growth of GDE To achieve the CO2 emission peaking target and substantially promote the low-carbon deve!opment transformation, China needs to actively promote an energy production and consumption revolution, the innovation of advanced energy technologies, the reform of the energy regulatory system and pricing mechanism, and especially the construction of a national carbon emission cap and trade system.

Intelligent Passive Detection of Aerial Target in Space-Air-Ground Integrated Networks

Passive detection of moving target is an important part of intelligent surveillance. Satellite has the potential to play a key role in many applications of space-air-ground integrated networks(SAGIN). In this paper, we propose a novel intelligent passive detection method for aerial target based on reservoir computing networks. Specifically, delayed feedback networks are utilized to refine the direct signals from the satellite in the reference channels. In addition, the satellite direct wave interference in the monitoring channels adopts adaptive interference suppression using the minimum mean square error filter. Furthermore, we employ decoupling echo state networks to predict the clutter interference in the monitoring channels and construct the detection statistics accordingly. Finally, a multilayer perceptron is adopted to detect the echo signal after interference suppression. Extensive simulations is conducted to evaluate the performance of our proposed method. Results show that the detection probability is almost 100% when the signal-to-interference ratio of echo signal is-36 dB, which demonstrates that our proposed method achieves efficient passive detection for aerial targets in typical SAGIN scenarios.

Multi-target range and velocity measurements of a digital phased array radar system

As the core of a digital phased array radar system,a radar signal processing environment is created to measure multitarget range and velocity information. The radar echo signal is achieved by superposing target echo, noise, clutter and jamming signals linearly. Considering that these signals have many types,two typical combinations are selected to construct the multi-target echo signal and the simulated echo signal is used as the input of the signal processing environment. This environment mainly adopts pulse compression,moving target indication and detection technologies to process the echo signal.It is found that the frequency domain method is more desirable for the pulse compression effect than the time domain method,and multi-target range information can be measured from the moving target indication result after using a double delay canceller. A new moving target detecting method is proposed,which can present the positive and negative velocity accurately with the multi-target range and velocity measured simultaneously. Simulation results indicate that the potential targets are detected from the chaotic radar echo signals successfully,and their range and velocity can be figured out correctly in the built radar signal processing environment.

A line laser detection screen design and projectile echo power calculation in detection screen area

A line laser with high power as the background light source for the design of a new photoelectric detection target is proposed in this paper, aiming to improve the detection ability of the traditional photoelectric detection target under low background illumination. The laser emitted pulse waveform function and the laser echo pulse response function were used to establish the mathematical model of the reflected echo power of projectile in the detection area and derive the calculation function of minimum detectable echo power in the line laser detection screen, according to information of the line laser emitted power, incident angle of projectile, duration time and detection distance of projectile passing through the line laser detection screen. Calculations and experimental results showed that the design method of line laser detection screen and calculation model of laser echo power are reasonable, and the detection ability of line laser detection screen is obviously higher than that of traditional photoelectric detection screen, especially in low background illumination;at the same time, the designed line laser detection screen was used to combine a six line laser detection screen intersection test system, based on live ammunition for shooting. The test system is stable and able to obtain the dynamic parameters of the flying projectile, verifying that the design of the line laser detection screen in new photoelectric detection target can be suitable for shooting range test applications.

Proteolysis targeting chimera technology:a novel strategy for treating diseases of the central nervous system

Neurological diseases such as stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking.Proteolysis targeting chimera(PROTAC)technology is a novel strategy to solve this problem.PROTAC technology uses the ubiquitin-protease system to eliminate mutated,denatured,and harmful proteins in cells.It can be reused,and utilizes the protein destruction mechanism of the cells,thus making up for the deficiencies of traditional protein degradation methods.It can effectively target and degrade proteins,including proteins that are difficult to identify and bind.Therefore,it has extremely important implications for drug development and the treatment of neurological diseases.At present,the targeted degradation of mutant BTK,mHTT,Tau,EGFR,and other proteins using PROTAC technology is gaining attention.It is expected that corresponding treatment of nervous system diseases can be achieved.This review first focuses on the recent developments in PROTAC technology in terms of protein degradation,drug production,and treatment of central nervous system diseases,and then discusses its limitations.This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases.

Automatic target tracking on multi-resolution terrain

We propose a high-performance path planning algorithm for automatic target tracking in the applications of real-time simulation and visualization of large-scale terrain datasets, with a large number of moving objects （such as vehicles） tracking multiple moving targets. By using a modified Dijkstra＇s algorithm, an optimal path between each vehicle-target pair over a weighted grid-presented terrain is computed and updated to eliminate the problem of local minima and losing of tracking. Then, a dynamic path re-planning strategy using multi-resolution representation of a dynamic updating region is proposed to achieve high-performance by trading-off precision for efficiency, while guaranteeing accuracy. Primary experimental results showed that our algorithm successfully achieved l0 to 96 frames per second interactive path-replanning rates during a terrain simulation scenario with 10 to 100 vehicles and multiple moving targets.