Outcomes and efficacy of magnetic resonance imaging-compatible sacral nerve stimulator for management of fecal incontinence: A multi-institutional study

BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.

Preface

During April 20-22,2022,colleagues and friends gathered at the Institute of Pure&Applied Mathematics(IPAM),at the University of California at Los Angeles to celebrate Professor Stanley Osher's 8Oth birthday in a conference focusing on recent developments in"Optimization,Shape analysis,High-dimensional differential equations in science and Engineering,and machine learning Research(OSHER)"This conference hosted in-person talks by mathematicians,scientists,and industrial professionals worldwide.Those who could not attend extended their warm regards and expressed their appreciation for Professor Osher.

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Navigating the complexities of perianal Crohn’s disease:Diagnostic strategies,treatment approaches,and future perspectives

This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,characterized by its chronic and relapsing nature,is an idiopathic condition that can involve any segment of the gastrointestinal tract.Perianal disease impacts up to 40%of patients with CD,with perianal fistulas constituting up to 80%of perianal lesions.Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients.The management focuses on controlling the perianal sepsis and treating luminal CD.Biologics are crucial to the treatment approach,and results have been encouraging.The surgery focuses on controlling the sepsis,with more definitive treatments being fistula surgery,fecal diversion,and proctectomy as the last resort.This manuscript briefly describes the burden of CD,the challenges posed by perianal CD,and the role of different treatment modalities from colorectal surgeon’s perspective.

Lax-Oleinik-Type Formulas and Efficient Algorithms for Certain High-Dimensional Optimal Control Problems

Two of the main challenges in optimal control are solving problems with state-dependent running costs and developing efficient numerical solvers that are computationally tractable in high dimensions.In this paper,we provide analytical solutions to certain optimal control problems whose running cost depends on the state variable and with constraints on the control.We also provide Lax-Oleinik-type representation formulas for the corresponding Hamilton-Jacobi partial differential equations with state-dependent Hamiltonians.Additionally,we present an efficient,grid-free numerical solver based on our representation formulas,which is shown to scale linearly with the state dimension,and thus,to overcome the curse of dimensionality.Using existing optimization methods and the min-plus technique,we extend our numerical solvers to address more general classes of convex and nonconvex initial costs.We demonstrate the capabilities of our numerical solvers using implementations on a central processing unit(CPU)and a field-programmable gate array(FPGA).In several cases,our FPGA implementation obtains over a 10 times speedup compared to the CPU,which demonstrates the promising performance boosts FPGAs can achieve.Our numerical results show that our solvers have the potential to serve as a building block for solving broader classes of high-dimensional optimal control problems in real-time.

Efficient Finite Difference WENO Scheme for Hyperbolic Systems withNon-conservativeProducts

Higher order finite difference weighted essentially non-oscillatory(WENO)schemes have been constructed for conservation laws.For multidimensional problems,they offer a high order accuracy at a fraction of the cost of a finite volume WENO or DG scheme of the comparable accuracy.This makes them quite attractive for several science and engineering applications.But,to the best of our knowledge,such schemes have not been extended to non-linear hyperbolic systems with non-conservative products.In this paper,we perform such an extension which improves the domain of the applicability of such schemes.The extension is carried out by writing the scheme in fluctuation form.We use the HLLI Riemann solver of Dumbser and Balsara(J.Comput.Phys.304:275-319,2016)as a building block for carrying out this extension.Because of the use of an HLL building block,the resulting scheme has a proper supersonic limit.The use of anti-diffusive fluxes ensures that stationary discontinuities can be preserved by the scheme,thus expanding its domain of the applicability.Our new finite difference WENO formulation uses the same WENO reconstruction that was used in classical versions,making it very easy for users to transition over to the present formulation.For conservation laws,the new finite difference WENO is shown to perform as well as the classical version of finite difference WENO,with two major advantages:(i)It can capture jumps in stationary linearly degenerate wave families exactly.(i)It only requires the reconstruction to be applied once.Several examples from hyperbolic PDE systems with non-conservative products are shown which indicate that the scheme works and achieves its design order of the accuracy for smooth multidimensional flows.Stringent Riemann problems and several novel multidimensional problems that are drawn from compressible Baer-Nunziato multiphase flow,multiphase debris flow and twolayer shallow water equations are also shown to document the robustness of the method.For some test problems that require well-balancing we have even been able to apply the scheme without any modification and obtain good results.Many useful PDEs may have stiff relaxation source terms for which the finite difference formulation of WENO is shown to provide some genuine advantages.

Long Term X-Ray Spectral Variations of the Seyfert-1 Galaxy Mrk 279

We present the results from a long term X-ray analysis of Mrk 279 during the period 2018–2020.We use data from multiple missions–AstroSat,NuSTAR and XMM-Newton,for the purpose.The X-ray spectrum can be modeled as a double Comptonization along with the presence of neutral Fe Kαline emission,at all epochs.We determined the source’s X-ray flux and luminosity at these different epochs.We find significant variations in the source’s flux state.We also investigate the variations in the source’s spectral components during the observation period.We find that the photon index and hence the spectral shape follow the variations only over longer time periods.We probe the correlations between fluxes of different bands and their photon indices,and found no significant correlations between the parameters.

Preface

This focused issue of the Communications on Applied Mathematics and Computation is dedicated to the memory of Professor Ching-Shan Chou,who passed away in November 2021.With her passing,our community of applied mathematicians lost not only a brilliant researcher but also a cherished friend and colleague.

RKDG Methods with Multi-resolution WENO Limiters for Solving Steady-State Problems on Triangular Meshes

In this paper, we design high-order Runge-Kutta discontinuous Galerkin (RKDG) methods with multi-resolution weighted essentially non-oscillatory (multi-resolution WENO) limiters to compute compressible steady-state problems on triangular meshes. A troubled cell indicator extended from structured meshes to unstructured meshes is constructed to identify triangular cells in which the application of the limiting procedures is required. In such troubled cells, the multi-resolution WENO limiting methods are used to the hierarchical L^(2) projection polynomial sequence of the DG solution. Through using the RKDG methods with multi-resolution WENO limiters, the optimal high-order accuracy can be gradually reduced to first-order in the triangular troubled cells, so that the shock wave oscillations can be well suppressed. In steady-state simulations on triangular meshes, the numerical residual converges to near machine zero. The proposed spatial reconstruction methods enhance the robustness of classical DG methods on triangular meshes. The good results of these RKDG methods with multi-resolution WENO limiters are verified by a series of two-dimensional steady-state problems.

Verification and Validation of High-Resolution Inviscid and Viscous Conical Nozzle Flows

Capturing elaborated flow structures and phenomena is required for well-solved numerical flows.The finite difference methods allow simple discretization of mesh and model equations.However,they need simpler meshes,e.g.,rectangular.The inverse Lax-Wendroff(ILW)procedure can handle complex geometries for rectangular meshes.High-resolution and high-order methods can capture elaborated flow structures and phenomena.They also have strong mathematical and physical backgrounds,such as positivity-preserving,jump conditions,and wave propagation concepts.We perceive an effort toward direct numerical simulation,for instance,regarding weighted essentially non-oscillatory(WENO)schemes.Thus,we propose to solve a challenging engineering application without turbulence models.We aim to verify and validate recent high-resolution and high-order methods.To check the solver accuracy,we solved vortex and Couette flows.Then,we solved inviscid and viscous nozzle flows for a conical profile.We employed the finite difference method,positivity-preserving Lax-Friedrichs splitting,high-resolution viscous terms discretization,fifth-order multi-resolution WENO,ILW,and third-order strong stability preserving Runge-Kutta.We showed the solver is high-order and captured elaborated flow structures and phenomena.One can see oblique shocks in both nozzle flows.In the viscous flow,we also captured a free-shock separation,recirculation,entrainment region,Mach disk,and the diamond-shaped pattern of nozzle flows.

Distinct and Additive Effects of Alcohol and Thiamine Deficiency in the Developing Brain: Relevance to Fetal Alcohol Spectrum Disorder

Background: Neurodevelopmental abnormalities in fetal alcohol spectrum disorder (FASD) are linked to brain insulin resistance and oxidative stress. However, the role of thiamine deficiency as a distinct or additive factor in the pathogenesis of the neurodevelopmental and metabolic derangements in FASD has not been determined. Methods: Control and ethanol-exposed human PNET2 cerebellar neuronal cells and rat cerebellar slice cultures were treated with vehicle or pyrithiamine (Pyr) to assess independent and additive effects of thiamine deficiency on ethanol-mediated neurotoxicity, mitochondrial dysfunction, insulin resistance, inhibition of neuronal and glial genes, and oxidative stress. Results: Pyr treatments (0 - 200 µM) caused dose-dependent cell loss (Crystal Violet assay) and reduced mitochondrial function (MTT assay) in PNET2 neuronal cultures. Ethanol alone (100 mM) significantly reduced PNET2 neuronal viability, MTT activity, and ATP production. Over the broad dose range of Pyr treatment, ethanol significantly reduced ATP content and cell number and increased mitochondrial mass (MitoTracker Green). Ex vivo cerebellar slice culture studies revealed ethanol-induced developmental architectural disruption that was substantially worsened by Pyr. The adverse effects of ethanol were linked to increased lipid peroxidation and inhibition of asparatyl-asparaginyl-β-hydroxylase (ASPH) expression. The independent and additive effects of Pyr were associated with increased cytotoxicity, lipid peroxidation, Caspase 3 activation, and Tau accumulation. Conclusions: During development, alcohol exposure and thiamine deficiency exert distinct but overlapping molecular pathologies that ultimately impair the structure and function of cerebellar neurons. While both insults drive cell loss and mitochondrial dysfunction with increased lipid peroxidation, ethanol’s additional inhibitory effects on ASPH reflect impairments in insulin and IGF signaling. In contrast, Pyr’s main adverse effects were likely due to neurotoxicity and the activation of apoptosis cascades. The findings suggest that FASD severity may be reduced by thiamine supplementation, but without additional support for insulin/IGF signaling networks, FASD would not be prevented.

Barriers in early detection of colorectal cancer and exploring potential solutions

This editorial discusses the literature review article by Tonini and Zanni,the paper was published in January 2024,and the authors provided very interesting conclusions regarding existing barriers to the early diagnosis of colon cancer.Many cancers do not have identifiable precursors,or there are currently no screening tests to find them.Therefore,these cancers do not have preventive screening options.Early detection is crucial for reducing mortality rates by identifying cancer at an earlier stage through screening,as opposed to no screening.Colorectal cancer develops from precancerous lesions,which can be detected early and potentially prevented and cured.Early detection leads to improved survival rates,decreased complications,and reduced healthcare expenses.This editorial provides a brief description of the biology of colon cancer,emphasizing the contrast in outcomes between early detection and late detection.We also describe screening programs around the globe and examine the barriers in each program.Finally,we explore potential future solutions to enhance inclusion in screening programs and improve patient compliance.

Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

LPCAT1在FAB-M2亚型成人急性髓系白血病患者中的预后意义

目的:研究溶血磷脂酰胆碱酰基转移酶1(LPCAT1)在急性髓系白血病(AML)中的预后价值。方法:使用基于Taq Man的逆转录-实时荧光定量聚合酶链反应检测214例初治成人AML患者和24例健康对照者LPCAT1的相对表达量。使用Kaplan-Meier方法进行生存分析,Cox比例风险回归模型用于确定预后因素。结果:LPCAT1在成人AML中的表达水平为34.37%(1.83%-392.63%),显著低于健康对照者的92.81%(2.60%-325.84%)(P<0.001)。本研究在具有完整临床信息和预后数据的171例非急性早幼粒细胞白血病患者中评估了LPCAT1的预后意义。生存分析结果表明,LPCAT1的表达水平对整个队列的预后没有显著影响。然而,在FAB-M2亚型(M2-AML)的AML患者中,低表达LPCAT1患者的2年无复发生存率为35.4%(95%CI:0.107-0.601),显著低于高表达LPCAT1患者的79.2%(95%CI:0.627-0.957)(P=0.012)。多因素分析结果表明,低表达LPCAT1是M2-AML患者无复发生存率的独立危险因素(HR=0.355,95%CI:0.126-0.966,P=0.049)。结论:LPCAT1在成人AML患者中低表达,LPCAT1低表达是M2-AML患者无复发生存率的独立危险因素。

Preface: machine-learning approaches for computational mechanics

Machine-learning(ML) approaches have gained significant attention in recent years for their potential to revolutionize various scientific research fields,including computational mechanics,materials science,and biomedical engineering.In the field of computational mechanics,various neural network models such as feedforward neural networks,convolutional neural networks.

Major depressive disorders in patients with inflammatory bowel disease and rheumatoid arthritis

BACKGROUND Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease(IBD)and rheumatoid arthritis(RA),are found to have a substantial societal burden,increased healthcare costs,and progressive disability.Studies suggest that patients with vs without comorbid depression have a more significant disability,a lower likelihood of remission,and reduced adherence to therapy.Elevated interleukin(IL)-1β,tumor necrosis factor-α,and IL-6 contribute to developing depression by the impaired physiological responses to stress,resulting in increased pain,fever,fatigue,and lack thereof of interest,and thus poor long-term outcomes.This study emphasizes the timely recognition of the prevalence of major depressive disorder(MDD)in patients with RA and IBD combined,thus preventing disability.AIM To identify the prevalence level and temporal trends of depression in hospitalized IBD-RA patients.METHODS All adult hospitalized patients from January 2000 to December 2019 in the nationwide inpatient sample(NIS)were captured.The study population included all patients with a primary or secondary IBD-RA overlap disease using corresponding international classification of diseases(ICD)-9 and ICD-10 codes.IBD includes Crohn’s disease and ulcerative colitis.The study population was divided into IBD-RA without MDD(controls)and IBD-RA with MDD(cases).For group comparison between MDD vs no MDD,we used Student’s t-test for continuous variables and RaoScott Chi-square tests for categorical variables.For univariate analyses,we used logistic regression,and for multivariate analysis,we used a weighted multi-level mixed-effects model.We attested all hypotheses with two-tailed significance level of 0.05(P<0.05 was considered significant).The outcome is to examine the temporal trends and prevalence of depression in patients with IBD-RA by gender,race,and age.RESULTS A total of 133315 records were identified with IBD-RA overlap,of which 26155 patients(19.62%)had MDD.Among the IBD-RA patients,those who had MDD were younger[mean age of 56 years(SD±15)]to IBD-RA without MDD patients with a P<0.0001,more females(80%among cases vs 73%among controls)than males with a P<0.0001,frequent in the white race(79%among cases vs 73%among controls)than black race.Over the 19 years,the number of patients with MDD in IBDRA increased from 153(the year 2000)to 2880(the year 2019)in weighted NIS,representing a 1782%increase compared to the year 2000 with a P<0.001.Factors associated with higher MDD included younger age,female gender,white race,alcohol,opioids,esophageal disorders,peptic ulcer disease,chronic pancreatitis,paralysis,dementia,menopausal disorders,obesity,nutritional deficiencies,diabetes mellitus with chronic complications,and osteoarthritis.CONCLUSION There is a rise in the prevalence of depression in younger patients with IBD-RA combined compared to their counterparts.These patients are also at higher risk for the increased cost of care and poor treatment compliance.It is crucial to educate the involved clinicians to identify the early signs and symptoms of depression in patients with IBD or RA or IBD-RA combined and treat them to have a better overall prognosis.

Federated Feature Concatenate Method for Heterogeneous Computing in Federated Learning

Federated learning is an emerging machine learning techniquethat enables clients to collaboratively train a deep learning model withoutuploading raw data to the aggregation server. Each client may be equippedwith different computing resources for model training. The client equippedwith a lower computing capability requires more time for model training,resulting in a prolonged training time in federated learning. Moreover, it mayfail to train the entire model because of the out-of-memory issue. This studyaims to tackle these problems and propose the federated feature concatenate(FedFC) method for federated learning considering heterogeneous clients.FedFC leverages the model splitting and feature concatenate for offloadinga portion of the training loads from clients to the aggregation server. Eachclient in FedFC can collaboratively train a model with different cutting layers.Therefore, the specific features learned in the deeper layer of the serversidemodel are more identical for the data class classification. Accordingly,FedFC can reduce the computation loading for the resource-constrainedclient and accelerate the convergence time. The performance effectiveness isverified by considering different dataset scenarios, such as data and classimbalance for the participant clients in the experiments. The performanceimpacts of different cutting layers are evaluated during the model training.The experimental results show that the co-adapted features have a criticalimpact on the adequate classification of the deep learning model. Overall,FedFC not only shortens the convergence time, but also improves the bestaccuracy by up to 5.9% and 14.5% when compared to conventional federatedlearning and splitfed, respectively. In conclusion, the proposed approach isfeasible and effective for heterogeneous clients in federated learning.

FAR591 promotes the pathogenesis and progression of SONFH by regulating Fos expression to mediate the apoptosis of bone microvascular endothelial cells

The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding RNAs(lnc RNAs)in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment.In this study,we first confirmed that glucocorticoid(GC)-induced apoptosis of bone microvascular endothelial cells(BMECs)is a pre-event in the pathogenesis and progression of SONFH.Then,we identified a new lnc RNA in BMECs via lnc RNA/m RNA microarray,termed Fosassociated linc RNA ENSRNOT00000088059.1(FAR591).FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis.Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs,which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH.In contrast,overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs,which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH.Mechanistically,GCs activate the glucocorticoid receptor,which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression.Subsequently,FAR591 binds to the Fos gene promoter(–245–51)to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation.Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death(Bim)and P53 upregulated modulator of apoptosis(Puma)to mediate GC-induced apoptosis of BMECs,which leads to femoral head microcirculation dysfunction and femoral head necrosis.In conclusion,these results confirm the mechanistic link between lnc RNAs and the pathogenesis of SONFH,which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.

Combination of transarterial radioembolization with atezolizumab and bevacizumab for intermediate and advanced staged hepatocellular carcinoma:A preliminary report of safety and feasibility

Purpose:The IMbrave150 PhaseⅢtrial demonstrated superiority of atezolizumab and bevacizumab(Atezo/Bev)over sorafenib for unresectable hepatocellular carcinoma(HCC).The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for treatment of intermediate and advanced staged HCC.Methods:Retrospective review at a single institution was performed between May 2021 and December 2022.Patients who received TARE using yttrium-90(Y90)with concomitant or sequential Atezo/Bev systemic treatment were included.The following outcomes were retrieved:overall survival(OS),radiologic tumor response,progression-free survival,technical adverse events related to TARE,and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0.Results:Ten consecutive patients with intermediate(n=4)and advanced stage HCC(n=6)were treated with TARE and sequential/concomitant Atezo/Bev.Tumor control was achieved in all TARE-treated target lesions(100%).Overall disease progression occurred in 4 patients with PFS of 78.8%and 66.7%at 6-and 12-months,respectively.Two patients died at follow-up,with 6-month and 12-month OS rates of 90.0%and 77.1%,respectively.Three(75%)patients with intermediate stage disease were downstaged into Milan criteria.One patient developed grade 3 transaminitis and hypoglobulinemia,while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis.Conclusion:This study demonstrates initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC.Further prospective studies with larger sample size are warranted.

Study of Central Intensity Ratio of Seyfert Galaxies in Nearby Universe

We use the recently discovered simple photometric parameter Central Intensity Ratio(CIR)determined for a sample of 57 nearby(z<0.02)Seyfert galaxies to explore the central features of galaxies and their possible connection with galaxy evolution.The sample of galaxies shows strong anti-correlation between CIR and mass of their central supermassive black holes(SMBHs).The SMBH masses of ellipticals are systematically higher for a given CIR value than those for lenticulars and spirals in the sample.However,the correlation between CIR and central velocity dispersion is weak.CIR appears less influenced by the excess flux produced by the central engine in these galaxies,when compared to spectroscopic parameters like velocity dispersion and OⅣflux,and proves to be a fast and reliable tool for estimating central SMBH mass.