Monitoring the Short-Term Response to Salt Exposure of Two Genetically Distinct <i>Phragmites australis</i>Clones with Different Salinity Tolerance Levels

Aims: Two genetically distinct clones of Phragmites australis were used to investigate the immediate response induced by osmotic stress. The study aimed at elucidating if the response time, the inhibition rate and the recovery from salinity stress vary between these two genotypes. The experimental work was conducted at the laboratory of the Institute of Bioscience, Aarhus University, Denmark. Methods: The light-saturated photosynthetic rate (Pmax), stomata conductance (gs) and transpiration rate (E) were measured over different periods of salt exposure (15, 70 and 240 minutes) and at different salt concentrations (20 and 40 parts per thousand salinity). Important findings: The osmotic stress induced stomata closure and reduction of Pmax and E for both clones. The clone-specific responses as measured through physiological parameters were negatively correlated with exposure time and salt concentration. During the 4-hour exposure at 20 ppt, the two clones were inhibited at different rates. The salt-sensitive Land-type showed an immediate reduction of Pmax, gs and E. No recovery was observed after removing the salt solution. At the same salt concentration, the reduction of Pmax gs and E of the Greeny-type was lower and immediate recovery was observed when the root zone was rinsed. Both clones were irreversibly inhibited after 4 hours of exposure to 40 ppt. Recovery was primarily related to exposure time, as Pmax, gs and E rates of both clones recovered completely after fresh-water rinsing in the 15-minute experiment. The Greeny-type also recovered after the 70-minute exposure, but not the Land-type.

Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

Study of A Hybrid Deep Learning Method for Forecasting the Short-Term Motion Responses of A Semi-Submersible

Accurately predicting motion responses is a crucial component of the design process for floating offshore structures.This study introduces a hybrid model that integrates a convolutional neural network(CNN),a bidirectional long short-term memory(BiLSTM)neural network,and an attention mechanism for forecasting the short-term motion responses of a semisubmersible.First,the motions are processed through the CNN for feature extraction.The extracted features are subsequently utilized by the BiLSTM network to forecast future motions.To enhance the predictive capability of the neural networks,an attention mechanism is integrated.In addition to the hybrid model,the BiLSTM is independently employed to forecast the motion responses of the semi-submersible,serving as benchmark results for comparison.Furthermore,both the 1D and 2D convolutions are conducted to check the influence of the convolutional dimensionality on the predicted results.The results demonstrate that the hybrid 1D CNN-BiLSTM network with an attention mechanism outperforms all other models in accurately predicting motion responses.

An efficient conversion model between acceleration and pseudo-acceleration response spectra considering effects of magnitude,distance,and site class

Both acceleration and pseudo-acceleration response spectra play important roles in structural seismic design.However,only one of them is generally provided in most seismic codes.Therefore,many studies have attempted to develop conversion models between the acceleration response spectrum(SA)and the pseudo-acceleration response spectrum(PSA).Our previous studies found that the relationship between SA and PSA is affected by magnitude,distance,and site class.Subsequently,we developed an SA/PSA model incorporating these effects.However,this model is suitable for cases with small and moderate magnitudes and its accuracy is not good enough for cases with large magnitudes.This paper aims to develop an efficient SA/PSA model by considering influences of magnitude,distance,and site class,which can be applied to cases not only with small or moderate magnitudes but also with large ones.For this purpose,regression analyses were conducted using 16,660 horizontal seismic records with a wider range of magnitude.The magnitude of these seismic records varies from 4 to 9 and the distances vary from 10 to 200 km.These ground motions were recorded at 338 stations covering four site classes.By comparing them with existing models,it was found that the proposed model shows better accuracy for cases with any magnitudes,distances,and site classes considered in this study.

Vibration response of Euler-Bernoulli-damped beam with appendages subjected to a moving mass

This paper addresses the problem of a viscoelastic Euler-Bernoulli beam under the influence of a constant velocity moving mass and different types of appendages.Four types of boundary conditions are considered:pinned-pinned,fixed-pinned,fixed-free(or cantilever),and fixed-fixed.Appendages considered include lumped masses,dampers,and springs.The modal decomposition method is employed to derive the equation of motion of the beam,for which an analytical closed-form expression of the dynamic vibration response is generated.The proposed method enables the study of the effect of a single appendage or a combination of the three types of appendages on the non-dimensional dynamic response of the beam.Numerical examples are presented to illustrate the effects of these appendages and compare them to the reference cases of a beam with no appendages.The results demonstrate the importance of considering these parameters in the design of structures.The proposed method is compared to other techniques in the literature and found to be advantageous due to its direct approach.The method also offers a versatile tool for investigating various configurations,aiding in engineering design and structural analysis for which establishing a precise prediction of beam vibrations is crucial.

Analysis of vibration response characteristics of subway station and superstructure with hard combination

The vibration response and noise caused by subway trains can affect the safety and comfort of superstructures.To study the dynamic response characteristics of subway stations and superstructures under train loads with a hard combination,a numerical model is developed in this study.The indoor model test verified the accuracy of the numerical model.The influence laws of different hard combinations,train operating speeds and modes were studied and evaluated accordingly.The results show that the frequency corresponding to the peak vibration acceleration level of each floor of the superstructure property is concentrated at 10–20 Hz.The vibration response decreases in the high-frequency parts and increases in the lowfrequency parts with increasing distance from the source.Furthermore,the factors,such as train operating speed,operating mode,and hard combination type,will affect the vibration of the superstructure.The vibration response under the reversible operation of the train is greater than that of the unidirectional operation.The operating speed of the train is proportional to its vibration response.The vibration amplification area appears between the middle and the top of the superstructure at a higher train speed.Its vibration acceleration level will exceed the limit value of relevant regulations,and vibration-damping measures are required.Within the scope of application,this study provides some suggestions for constructing subway stations and superstructures.

Comparison of biomechanical indices measured by ocular response analyzer between children and elderly:a systematic review

Biomechanical study of the visual system by ocular response analyzer investigates the inter-structural biological relationships,mechanics,and function of the visual system.This review aimed to investigate the changes in corneal biomechanical parameters with age and sex.The articles published in PubMed between 2000 and 2021 were investigated and critiqued,and valid scientific evidence was collected,reviewed and concluded according to the inclusion and exclusion criteria.Most studies showed that corneal biomechanical changes occur infrequently in children up to the age of 20y,and with increasing age and wider age range,there was a significant decrease in corneal biomechanical indices,especially corneal hysteresis.In children and adults,most studies have shown that these biomechanical indicators,especially corneal resistance factor,were higher in females.Although hormonal changes may contribute to this finding,the role of axial length and other biometric indicators should not be ignored.The axial length,the intraocular pressure,and the corneal thickness are other factors associated with biomechanical parameters that should be taken into account in clinical diagnosis and management especially for patients undergoing refractive surgery as well as keratoconus patients.

Genome-wide identification and characterization of putative effectors in Heterodera schachtii that suppress plant immune response

The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.

Visual electrophysiological assessment of children with poor response to treatment for functional amblyopia

AIM:To assess the visual electrophysiological outcomes in children with functional amblyopia who exhibited poor response to conventional treatment.METHODS:Twenty-one children with functional amblyopia,aged 5.7±2.1y(range:4-10y),underwent comprehensive ophthalmic and refractive evaluations.Spectral domain-optical coherence tomography(SD-OCT)and multifocal electroretinography(mfERG)were conducted to analyze the macular retinal thickness and the first-order response P1 ring of the mfERG in the amblyopic eye(AE)compared to the fellow good eye(GE).RESULTS:Initially,visual acuity in the AE ranged from 20/800 to 20/40,while the GE exhibited a range of 20/25 to 20/20(P<0.01).After 6mo of treatment,17 patients demonstrated improved visual acuity in the AE to 20/50 or better,while 4 children showed no improvement.SD-OCT revealed comparable macular and optic disc structures between the AE and GE.Prior to treatment,the mfERG P1 ring amplitude was significantly reduced in the AE compared to GE(P<0.05).The AE/GE ratio of P1 ring amplitude showed significant improvement post-treatment.However,a smaller AE/GE ratio before treatment was associated with poorer improvement post-treatment.CONCLUSION:In the management of functional amblyopia,a thorough assessment of amblyopic eye examinations is crucial.Approximately 20%of amblyopic eyes may not achieve significant improvement in visual acuity,despite the absence of detectable organic retinal abnormalities.mfERG may reveal underlying abnormalities.Integrating mfERG into initial assessments or treatment follow-ups can aid in identifying potential hidden retinal defects and predicting the prognosis of the amblyopic eye.

Experimental investigations on combined high and low cycle fatigue:Material-level specimen design and strain response characteristics

The paper designs a novel material-level specimen and its dedicated fixture suitable for applying Combined high-and low-Cycle Fatigue(CCF)loads.Unlike full-scale or simulation specimens,the CCF specimen eliminates geometrically induced stress gradients in the test region.Experimental data on CCF life and strain responses of ZSGH4169 alloy are acquired under different CCF loads.The Maximum Strain within Each(MSE)CCF cycle is demonstrated to be independent of the Low-Cycle Fatigue(LCF)loads and High-Cycle Fatigue(HCF)stress amplitudes,but exhibits a correlation with the Cycle Ratio of HCF/LCF(Rf).The growth law of MSE changes from linear to logarithmic as Rfdecreases.Strain amplitudes in the dwell stage,observed unaffected by Rf,are quantified as a function of LCF nominal stresses and HCF stress amplitudes.However,under a defined CCF load,strain amplitudes in the dwell stage remain constant.Strain peaks in the dwell stage in a single CCF cycle decrease in a power function with increasing HCF cycles.

Laparoscopic hepatectomy using indocyanine green attenuates postoperative inflammatory response for hepatocellular carcinoma:A propensity score matching analysis

BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver surgeons.AIM To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after surgery.METHODS We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June 2023.Whether using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG groups.To eliminate statistical bias,a 1:1 propensity score matching analysis was conducted.The comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed statistically.RESULTS Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO time.Postoperatively,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,P<0.05).Although the differences were not significant,the levels of all inflammation-related markers were lower in the ICG group.The rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the groups.CONCLUSION The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.

Effect of Modulen vs budesonide on clinical response and mucosal healing in Crohn’s patients

BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.

Genetic factors that predict response and failure of biologic therapy in inflammatory bowel disease

Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.

Computed tomography-based delta-radiomics enabling early prediction ofshort-term responses to concurrent chemoradiotherapy for patients withnon-small cell lung cancer

Objective:To explore the potential of computed tomography(CT)-based delta-radiomics in predicting early shortterm responses to concurrent chemoradiotherapy for patients with non-small cell lung cancer(NSCLC),in order to determine the optimal time point for the prediction.Methods:A total of 20 patients with pathologically confirmed NSCLC were prospectively enrolled in this study,who did not receive surgical treatment between February 2021 and February 2022.For each case,a total of 1,210 radiomic features(RFs)were extracted from both planning CT(pCT)images along with each of the subsequent three weeks of CT images.EffectiveΔRFs were selected using intra-class correlation coefficient(ICC)analysis,Pearson's correlation,ANOVA test(or Mann-Whitney U-test),and univariate logistic regression.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the potential to predict short-term responses of different time points.Results:Among the 1,210ΔRFs for 1-3 weeks,121 common features were retained after processing using ICC analysis and Pearson's correlation.These retained features included 54 and 58 of all time points that differed significantly between the response and non-response groups for the first and third months,respectively(P<0.05).After univariate logistic regression,11 and 44 features remained for the first and third months,respectively.Finally,eightΔRFs(P<0.05,AUC=0.77-0.91)that can discriminate short-term responses in both at 1 and 3 months with statistical accuracy were identified.Conclusion:CT-based delta-radiomics has the potential to provide reasonable biomarkers of short-term responses to concurrent chemoradiotherapy for NSCLC patients,and it can help improve clinical decisions for early treatment adaptation.

LncRNA pol-lnc78 as a ceRNA regulates antibacterial responses via suppression of pol-miR-n199-3p-mediated SARM down-regulation in Paralichthys olivaceus

Long non-coding RNAs(lncRNAs)function as key modulators in mammalian immunity,particularly due to their involvement in lncRNA-mediated competitive endogenous RNA(ceRNA)crosstalk.Despite their recognized significance in mammals,research on lncRNAs in lower vertebrates remains limited.In the present study,we characterized the first immune-related lncRNA(pol-lnc78)in the teleost Japanese flounder(Paralichthys olivaceus).Results indicated that pol-lnc78 acted as a ceRNA for pol-miR-n199-3p to target the sterile alpha and armadillo motif-containing protein(SARM),the fifth discovered member of the Toll/interleukin 1(IL-1)receptor(TIR)adaptor family.This ceRNA network regulated the antibacterial responses of flounder via the Toll-like receptor(TLR)signaling pathway.Specifically,SARM acted as a negative regulator and exacerbated bacterial infection by inhibiting the expression of inflammatory cytokines IL-1βand tumor necrosis factor-α(TNF-α).Pol-miR-n199-3p reduced SARM expression by specifically interacting with the 3’untranslated region(UTR),thereby promoting SARM-dependent inflammatory cytokine expression and protecting the host against bacterial dissemination.Furthermore,pol-lnc78 sponged pol-miR-n199-3p to ameliorate the inhibition of SARM expression.During infection,the negative regulators pol-lnc78 and SARM were significantly down-regulated,while pol-miR-n199-3p was significantly up-regulated,thus favoring host antibacterial defense.These findings provide novel insights into the mechanisms underlying fish immunity and open new horizons to better understand ceRNA crosstalk in lower vertebrates.

A theory for three-dimensional response of micropolar plates

Through combined applications of the transfer-matrix method and asymptotic expansion technique,we formulate a theory to predict the three-dimensional response of micropolar plates.No ad hoc assumptions regarding through-thickness assumptions of the field variables are made,and the governing equations are two-dimensional,with the displacements and microrotations of the mid-plane as the unknowns.Once the deformation of the mid-plane is solved,a three-dimensional micropolar elastic field within the plate is generated,which is exact up to the second order except in the boundary region close to the plate edge.As an illustrative example,the bending of a clamped infinitely long plate caused by a uniformly distributed transverse force is analyzed and discussed in detail.

Thermo-hydro-poro-mechanical responses of a reservoir-induced landslide tracked by high-resolution fiber optic sensing nerves

Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.e.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.

Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).