Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

Integral sliding mode control of time-delay systems with mismatching uncertainties

A linear matrix inequality （LMI）-based sliding surface design method for integral sliding mode control of uncertain time- delay systems with mismatching uncertainties is proposed. The uncertain time-delay system under consideration may have mis- matching norm bounded uncertainties in the state matrix as well as the input matrix, A sufficient condition for the existence of a sliding surface is given to guarantee asymptotic stability of the full order slJdJng mode dynamics. An LMI characterization of the slid- ing surface is given, together with an integral sliding mode control law guaranteeing the existence of a sliding mode from the initial time. Finally, a simulation is given to show the effectiveness of the proposed method.

Channel Mismatching in Sidelobe Canceler: Limitations and Remedies

After a brief recall of the Sidelobe Canceler (SLC) working principle, including the derivation of a general formula for the Cancellation Ratio (CR), the effects of channel mismatching are investigated. In particular, curves providing CRvalues as a function of amplitude and phase channel mismatching, radar bandwidth, and jammer direction of arrival (JDOA) are provided for the cases of one and two auxiliary antennas. Subsequently, a time -space processor for performance restoration is analyzed in detail. In addition to the above mentioned quantities, the attainable CR value is expressed as a function of the space-time processor parameters. The contribution of the paper is related to the derivation of a number of mathematical equations of CR for several cases of practical interest for the radar engineer. In addition, several curves are presented to assist design of SLC systems.

Optimal PV Array Configuration for Extracting Maximum Power Under Partial Shading Conditions by Mitigating Mismatching Power Losses

The grid-connected or standalone PV central inverter architecture is comprised of several PV modules which are connected in different ways to form the PV array.The power generation capability of the PV array is primarily affected by partial shading conditions(PSC).Due to PSCs,the power output of the PV array is dramatically reduced,and mismatching losses are induced in the PV modules.Based on the extent of these problems,multiple peaks also appear in the power-voltage(P-V)curve,which makes it very difficult to track the global maximum power point(GMPP).The main objective of this research paper is to model and simulate the series(S),series-parallel(SP),bridge-link(BL),honey-comb(HC),total-cross-tied(TCT)and proposed triple-tied(TT)solar PV array configurations under various partial shading scenarios.The performance of all PV configurations is evaluated under a uniform approach,considering eight different shading scenarios.The performance of the considered PV configurations is analyzed in terms of their mismatching power losses,fill factors,efficiency,global maximum power points(GMPPs),local maximum power points(LMPPs),voltages and currents at GMPPs,open circuit voltage and short circuit currents.The above-mentioned PV configurations are modeled and simulated in a Matlab/Simulink environment by considering the KC-200GT module parameters.

Method for eliminating mismatching error in monolithic triaxial ring resonators

Several results on optical-axis perturbation and elimination of the mismatching error C of a monolithic triaxial ring resonator （MTRR） are reported. Based on the augmented 5×5 ray matrix method, by simultaneously considering axial displacement of a mirror and the misalignments in three planar square ring resonators of a MTRR, the rules of optical-axis perturbation are obtained. The mismatching error C of the MTRR is eliminated. The results obtained are important for cavity design, as well as in the improvement and alignment of MTRR.

Phase-field simulations of the effect of temperature and interface for zirconiumδ-hydrides

Hydride precipitation in zirconium cladding materials can damage their integrity and durability.Service temperature and material defects have a significant effect on the dynamic growth of hydrides.In this study,we have developed a phasefield model based on the assumption of elastic behaviour within a specific temperature range(613 K-653 K).This model allows us to study the influence of temperature and interfacial effects on the morphology,stress,and average growth rate of zirconium hydride.The results suggest that changes in temperature and interfacial energy influence the length-to-thickness ratio and average growth rate of the hydride morphology.The ultimate determinant of hydride orientation is the loss of interfacial coherency,primarily induced by interfacial dislocation defects and quantifiable by the mismatch degree q.An escalation in interfacial coherency loss leads to a transition of hydride growth from horizontal to vertical,accompanied by the onset of redirection behaviour.Interestingly,redirection occurs at a critical mismatch level,denoted as qc,and remains unaffected by variations in temperature and interfacial energy.However,this redirection leads to an increase in the maximum stress,which may influence the direction of hydride crack propagation.This research highlights the importance of interfacial coherency and provides valuable insights into the morphology and growth kinetics of hydrides in zirconium alloys.

Seasonal increase in nest defense,but not egg rejection,in a cuckoo host

The interactions between avian brood parasites and their hosts provide an informative and easy-to-handle system for studying coevolution.Avian brood parasitism reduces the reproductive success of hosts,and thus,hosts have evolved anti-parasitic strategies,such as rejecting parasitic eggs and adopting aggressive nest defense strategies,to avoid the cost brought on by brood parasitism.To test whether host anti-parasitic strategies are adjusted with the risk of being parasitized when the breeding seasons of brood parasites and hosts are not synchronous,we conducted a field experiment assessing nest defense and egg recognition behaviors of the Isabelline Shrike(Lanius isabellinus),a host of the Common Cuckoo(Cuculus canorus).In the local area,the host Isabelline Shrike begins to breed in April,whereas the summer migratory Common Cuckoo migrates to the local area in May and begins to lay parasitic eggs.Results showed that nest defense behaviors of the Isabelline Shrike increases significantly after cuckoo arrival,showing higher aggressiveness to cuckoo dummies,with no significant difference in attack rates among cuckoo,sparrowhawk and dove dummies,but their egg rejection did not change significantly.These results imply that Isabelline Shrikes may adjust their nest defense behavior,but not egg rejection behavior,with seasonality.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Impacts of Model Mismatch and Array Scale on Channel Estimation for XL-HRIS-Aided Systems

Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

多模核磁MISMATCH技术在超时间窗急性大动脉闭塞性脑梗死患者治疗中的指导作用

目的 探讨多模核磁MISMATCH技术在超时间窗急性大动脉闭塞性脑梗死患者治疗中的指导作用。方法 选取2019年1月—2023年3月于天水市第一人民医院经多模核磁磁共振扩散加权成像(diffusion weighted imaging, DWI)-动脉自旋标记(arterial spin labeling, ASL)、DWI-液体衰减反转恢复(fluid attenuated inversion recovery, FLAIR)、DWI-磁敏感加权技术(magnetic sensitivity weighting technology, SWI)的MISMATCH技术进行筛选的超时间窗(发病时间在6~24 h)急性大动脉闭塞性脑梗死经血管内介入治疗患者44例作为研究组,同时选取在本中心超时间窗内(发病时间在6~24 h)未经多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术进行筛选的急性大动脉闭塞性脑梗死经血管内介入治疗患者43例作为对照组。研究组超时间窗患者术前均予以核磁共振扫描筛选出DWI-ASL/DWI-FLAIR/DWI-SWI其中存在MISMATCH且磁共振血管成像(magnetic resonance angiography, MRA)发现有大血管闭塞。两组患者都进行血管内介入治疗,治疗后血管血流均达到改良的脑梗死分级系统(modified treatment in cerebral ischemia, mTICI)分级2b/3级,观察两组患者的治疗获益和预后情况。结果 研究组术后90 d功能独立率(改良Rankin评分量表评分0~3分)为59.09%,高于对照组的37.21%,差异有统计学意义(χ^(2)=4.170,P<0.05)。研究组与对照组术后90 d病死率分别为25.00%与46.51%,研究组明显低于对照组,差异有统计学意义(P<0.05)。两组患者术后7 d美国国立卫生研究院卒中量表评分均低于术前,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组术后72 h症状性颅内出血与非症状性颅内出血发生率分别为22.73%、34.09%,对照组分别为44.19%、55.81%,研究组明显低于对照组,差异有统计学意义(P<0.05)。结论 经过多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术筛选出的超时间窗急性大动脉闭塞性脑梗死符合血管内治疗患者获益优于未经多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术进筛选的时间窗内急性大动脉闭塞性脑梗死患者获益,临床结局和安全性方面更好。

A polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure to improve the hole injection for GaN based micro-LED with secondary etched mesa

A low hole injection efficiency for InGaN/GaN micro-light-emitting diodes(μLEDs) has become one of the main bottlenecks affecting the improvement of the external quantum efficiency(EQE) and the optical power. In this work, we propose and fabricate a polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure for 445 nm GaN-based μLEDs with the size of 40 × 40 μm^(2), which serves as the hole injection layer. The polarization-induced electric field in the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure provides holes with more energy and can facilitate the non-equilibrium holes to transport into the active region for radiative recombination. Meanwhile, a secondary etched mesa for μLEDs is also designed, which can effectively keep the holes apart from the defected region of the mesa sidewalls, and the surface nonradiative recombination can be suppressed. Therefore, the proposed μLED with the secondary etched mesa and the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure has the enhanced EQE and the improved optical power density when compared with the μLED without such designs.

Measurement of the cavity-loaded quality factor in superconducting radio-frequency systems with mismatched source impedance

The accurate measurement of parameters such as the cavity-loaded quality factor(Q_(L))and half bandwidth(f_(0.5))is essential for monitoring the performance of superconducting radio-frequency cavities.However,the conventional"field decay method"employed to calibrate these values requires the cavity to satisfy a"zero-input"condition.This can be challenging when the source impedance is mismatched and produce nonzero forward signals(V_(f))that significantly affect the measurement accuracy.To address this limitation,we developed a modified version of the"field decay method"based on the cavity differential equation.The proposed approach enables the precise calibration of f_(0.5) even under mismatch conditions.We tested the proposed approach on the SRF cavities of the Chinese Accelerator-Driven System Front-End Demo Superconducting Linac and compared the results with those obtained from a network analyzer.The two sets of results were consistent,indicating the usefulness of the proposed approach.

The impact of market coordination on urban green total factor productivity:An analysis of the mediating effect of factor misallocation

Promoting market coordination and enhancing the efficiency of green growth is a necessity for China’s effective economic development.Using panel data from 2007 to 2020,this paper conducts a comprehensive study on 226 cities at the prefecture-level and above,combining theoretical analysis and empirical tests to systematically explore the impact of market cohesion on urban green total factor productivity(GTPF)and the mediating role of factor mismatch.Findings demonstrate that market coordination maximizes urban GTPF.At the mechanism level,factor mismatch plays a mediating role,and market coordination can enhance GTPF by addressing capital and labor mismatch.In terms of heterogeneity analysis,market coordination significantly promotes GTPF positively in the east-central region and negatively in the western region.In terms of technological progress and technical efficiency,the eastern region shows a larger significance than the central and western regions combined.In view of the above,the concept of market coordination development has been implemented to promote GTFP in cities.

A tunable adaptive detector for distributed targets when signal mismatch occurs

Aiming at the problem of detecting a distributed target when signal mismatch occurs,this paper proposes a tunable detector parameterized by an adjustable parameter.By adjusting the parameter,the tunable detector can achieve robust or selective detection of mismatched signals.Moreover,the proposed tunable detector,with a proper tunable parameter,can provide higher detection probability compared with existing detectors in the case of no signal mismatch.In addition,the proposed tunable detector possesses the constant false alarm rate property with the unknown noise covariance matrix.

Ambiguity function analysis and side peaks suppression of Link16 signal based passive radar

Link16 data link is the communication standard of the joint tactical information distribution system(JTIDS)used by the U.S.military and North Atlantic Treaty Organization,which is applied as the opportunistic illuminator for passive radar in this paper.The time-domain expression of the Link16 signal is established,and its ambiguity function expression is derived.The timedelay dimension and Doppler dimension side peaks of which lead to the appearance of the false target during target detection.To solve the problem,the time-delay dimension and Doppler dimension side peaks suppression methods are proposed.For the problem that the conventional mismatched filter(MMF)cannot suppress the time-delay dimension side peaks,a neighborhood MMF(NMMF)is proposed.Experimental results demonstrate the effectiveness of the proposed methods.