Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

Multilevel analysis of the central-peripheral-target organ pathway:contributing to recovery after peripheral nerve injury

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Carcinosarcoma of the breast:Facing the challenge of a rare nosologic entity

Carcinosarcoma(CS),also known as metaplastic breast carcinoma with mesenchymal differentiation,is one of the five distinct subtypes of metaplastic breast cancer.It is considered as a mixed,biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone.Although cellular origin of this neoplasm remains controversial,most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation.Despite recent research on the therapeutic strategies against CS neoplastic disorders,surgical resection appears the only potentially curative approach.Since CS metastasize by the lymphatic route,axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented.Nevertheless,the tumor also presents a hematogenous metastatic pattern including pleural,pulmonary,liver,brain and less commonly bone metastases.Thus,surgical removal of breast CS does not necessarily ensure patient’s long-term recovery.Moreover,alternative therapies,such as radio-and chemotherapy proved insufficient and 5-year survival rate is limited.Nevertheless,there is evidence that following surgery,the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone.The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread.Clinical features,histogenesis,morphological and immunochemical findings are discussed,while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

Enhancing perianal disease management with integrated physical and psychological approaches

This article provides a comprehensive analysis of the study by Hou et al,focusing on the complex interplay between psychological and physical factors in the postoperative recovery(POR)of patients with perianal diseases.The study sheds light on how illness perception,anxiety,and depression significantly influence recovery outcomes.Hou et al developed a predictive model that demonstrated high accuracy in identifying patients at risk of poor recovery.The article explores the critical role of pre-operative psychological assessment,highlighting the need for mental health support and personalized recovery plans in enhancing POR quality.A multidisciplinary approach,integrating mental health professionals with surgeons,anesthesiologists,and other specialists,is emphasized to ensure comprehensive care for patients.The study’s findings serve as a call to integrate psychological care into surgical practice to optimize outcomes for patients with perianal diseases.

Complication rates after direct anterior vs posterior approach for hip hemiarthroplasty in elderly individuals with femoral neck fractures

BACKGROUND Dislocation rates after hemiarthroplasty reportedly vary from 1%to 17%.This serious complication is associated with increased morbidity and mortality rates.Approaches to this surgery are still debated,with no consensus regarding the superiority of any single approach.AIM To compare early postoperative complications after implementing the direct anterior and posterior approaches(PL)for hip hemiarthroplasty after femoral neck fractures.METHODS This is a comparative,retrospective,single-center cohort study conducted at a university hospital.Between March 2008 and December 2018,273 patients(a total of 280 hips)underwent bipolar hemiarthroplasties(n=280)for displaced femoral neck fractures using either the PL(n=171)or the minimally invasive direct anterior approach(DAA)(n=109).The choice of approach was related to the surgeons’practices;the implant types were similar and unrelated to the approach.Dislocation rates and other complications were reviewed after a minimum followup of 6 mo.RESULTS Both treatment groups had similarly aged patients(mean age:82 years),sex ratios,patient body mass indexes,and patient comorbidities.Surgical data(surgery delay time,operative time,and blood loss volume)did not differ significantly between the groups.The 30 d mortality rate was higher in the PL group(9.9%)than in the DAA group(3.7%),but the difference was not statistically significant(P=0.052).Among the one-month survivors,a significantly higher rate of dislocation was observed in the PL group(14/154;9.1%)than in the DAA group(0/105;0%)(P=0.002).Of the 14 patients with dislocation,8 underwent revision surgery for recurrent instability(posterior group),and one of them had 2 additional procedures due to a deep infection.The rate of other complications(e.g.,perioperative and early postoperative periprosthetic fractures and infection-related complications)did not differ significantly between the groups.CONCLUSION These findings suggest that the DAA to bipolar hemiarthroplasty for patients with femoral neck fractures is associated with a lower dislocation rate(<1%)than the PL.

Observer-based robust high-order fully actuated attitude autopilot design for spinning glide-guided projectiles

This paper investigates the design of an attitude autopilot for a dual-channel controlled spinning glideguided projectile(SGGP),addressing model uncertainties and external disturbances.Based on fixed-time stable theory,a disturbance observer with integral sliding mode and adaptive techniques is proposed to mitigate total disturbance effects,irrespective of initial conditions.By introducing an error integral signal,the dynamics of the SGGP are transformed into two separate second-order fully actuated systems.Subsequently,employing the high-order fully actuated approach and a parametric approach,the nonlinear dynamics of the SGGP are recast into a constant linear closed-loop system,ensuring that the projectile's attitude asymptotically tracks the given goal with the desired eigenstructure.Under the proposed composite control framework,the ultimately uniformly bounded stability of the closed-loop system is rigorously demonstrated via the Lyapunov method.Validation of the effectiveness of the proposed attitude autopilot design is provided through extensive numerical simulations.

筛泡径路黏膜间隙追踪法在鼻内镜额窦开放术中的应用

目的应用黏膜延续性的特点,探讨黏膜间隙追踪法在临床中的应用。方法回顾性分析2021年1月~2023年1月间32例行黏膜间隙追踪法额窦开放术患者的临床资料,分析和记录术中情况以及随访观察恢复情况。结果黏膜间隙追踪法额窦开放手术时间短,手术并发症少。术后随访6个月以上,临床症状逐步消失,病变未复发。结论黏膜间隙追踪法可以将复杂关系的额隐窝手术简单化,提高手术安全性和手术效率。

Tailoring MXene Thickness and Functionalization for Enhanced Room‑Temperature Trace NO_(2) Sensing

In this study,precise control over the thickness and termination of Ti3C2TX MXene flakes is achieved to enhance their electrical properties,environmental stability,and gas-sensing performance.Utilizing a hybrid method involving high-pressure processing,stirring,and immiscible solutions,sub-100 nm MXene flake thickness is achieved within the MXene film on the Si-wafer.Functionalization control is achieved by defunctionalizing MXene at 650℃ under vacuum and H2 gas in a CVD furnace,followed by refunctionalization with iodine and bromine vaporization from a bubbler attached to the CVD.Notably,the introduction of iodine,which has a larger atomic size,lower electronegativity,reduce shielding effect,and lower hydrophilicity(contact angle:99°),profoundly affecting MXene.It improves the surface area(36.2 cm^(2) g^(-1)),oxidation stability in aqueous/ambient environments(21 days/80 days),and film conductivity(749 S m^(-1)).Additionally,it significantly enhances the gas-sensing performance,including the sensitivity(0.1119Ωppm^(-1)),response(0.2% and 23%to 50 ppb and 200 ppm NO_(2)),and response/recovery times(90/100 s).The reduced shielding effect of the–I-terminals and the metallic characteristics of MXene enhance the selectivity of I-MXene toward NO2.This approach paves the way for the development of stable and high-performance gas-sensing two-dimensional materials with promising prospects for future studies.

A FLEXIBLE OBJECTIVE-CONSTRAINT APPROACH AND A NEW ALGORITHM FOR CONSTRUCTING THE PARETO FRONT OF MULTIOBJECTIVE OPTIMIZATION PROBLEMS

In this article, a novel scalarization technique, called the improved objective-constraint approach, is introduced to find efficient solutions of a given multiobjective programming problem. The presented scalarized problem extends the objective-constraint problem. It is demonstrated that how adding variables to the scalarized problem, can lead to find conditions for (weakly, properly) Pareto optimal solutions. Applying the obtained necessary and sufficient conditions, two algorithms for generating the Pareto front approximation of bi-objective and three-objective programming problems are designed. These algorithms are easy to implement and can achieve an even approximation of (weakly, properly) Pareto optimal solutions. These algorithms can be generalized for optimization problems with more than three criterion functions, too. The effectiveness and capability of the algorithms are demonstrated in test problems.

Recent developments in selective laser processes for wearable devices

Recently,the increasing interest in wearable technology for personal healthcare and smart virtual/augmented reality applications has led to the development of facile fabrication methods.Lasers have long been used to develop original solutions to such challenging technological problems due to their remote,sterile,rapid,and site-selective processing of materials.In this review,recent developments in relevant laser processes are summarized under two separate categories.First,transformative approaches,such as for laser-induced graphene,are introduced.In addition to design optimization and the alteration of a native substrate,the latest advances under a transformative approach now enable more complex material compositions and multilayer device configurations through the simultaneous transformation of heterogeneous precursors,or the sequential addition of functional layers coupled with other electronic elements.In addition,the more conventional laser techniques,such as ablation,sintering,and synthesis,can still be used to enhance the functionality of an entire system through the expansion of applicable materials and the adoption of new mechanisms.Later,various wearable device components developed through the corresponding laser processes are discussed,with an emphasis on chemical/physical sensors and energy devices.In addition,special attention is given to applications that use multiple laser sources or processes,which lay the foundation for the all-laser fabrication of wearable devices.

Semi-analytical solution for drained expansion analysis of a hollow cylinder of critical state soils

The expansion of a thick-walled hollow cylinder in soil is of non-self-similar nature that the stress/deformation paths are not the same for different soil material points.As a result,this problem cannot be solved by the common self-similar-based similarity techniques.This paper proposes a novel,exact solution for rigorous drained expansion analysis of a hollow cylinder of critical state soils.Considering stress-dependent elastic moduli of soils,new analytical stress and displacement solutions for the nonself-similar problem are developed taking the small strain assumption in the elastic zone.In the plastic zone,the cavity expansion response is formulated into a set of first-order partial differential equations(PDEs)with the combination use of Eulerian and Lagrangian descriptions,and a novel solution algorithm is developed to efficiently solve this complex boundary value problem.The solution is presented in a general form and thus can be useful for a wide range of soils.With the new solution,the non-self-similar nature induced by the finite outer boundary is clearly demonstrated and highlighted,which is found to be greatly different to the behaviour of cavity expansion in infinite soil mass.The present solution may serve as a benchmark for verifying the performance of advanced numerical techniques with critical state soil models and be used to capture the finite boundary effect for pressuremeter tests in small-sized calibration chambers.

Exploring the transformative impact of traditional Chinese medicine on depression:Insights from animal models

Depression,a prevalent and complex mental health condition,presents a significant global health burden.Depression is one of the most frequent mental disorders;deaths from it account for 14.3%of people worldwide.In recent years,the integration of complementary and alternative medicine,including traditional Chinese medicine(TCM),has gained attention as a potential avenue for addressing depression.This comprehensive review critically assesses the efficacy of TCM interventions in alleviating depressive symptoms.An in-depth look at different research studies,clinical trials,and meta-analyses is used in this review to look into how TCM practices like herbal formulations,acupuncture,and mindbody practices work.The review looks at the quality of the evidence,the rigor of the methods,and any possible flaws in the current studies.This gives us an idea of where TCM stands right now in terms of treating depression.This comprehensive review aims to assess the efficacy of TCM interventions in alleviating depressive symptoms.In order to learn more about their possible healing effects,the study also looks into how different types of TCM work,such as herbal formulas,acupuncture,and mind-body practices.

Laparoscopic left hemihepatectomy guided by indocyanine green fluorescence: A cranial-dorsal approach

BACKGROUND Advancements in laparoscopic technology and a deeper understanding of intra-hepatic anatomy have led to the establishment of more precise laparoscopic hepatectomy(LH)techniques.The indocyanine green(ICG)fluorescence navi-gation technique has emerged as the most effective method for identifying hepatic regions,potentially overcoming the limitations of LH.While laparoscopic left hemihepatectomy(LLH)is a standardized procedure,there is a need for innova-tive strategies to enhance its outcomes.important anatomical markers,surgical skills,and ICG staining methods.METHODS Thirty-seven patients who underwent ICG fluorescence-guided LLH at Qujing Second People's Hospital between January 2019 and February 2022 were retrospectively analyzed.The cranial-dorsal approach was performed which involves dissecting the left hepatic vein cephalad,isolating the Arantius ligament,exposing the middle hepatic vein,and dissecting the parenchyma from the dorsal to the foot in order to complete the anatomical LLH.The surgical methods,as well as intra-and post-surgical data,were recorded and analyzed.Our hospital’s Medical Ethics Committee approved this study(Ethical review:2022-019-01).RESULTS Intraoperative blood loss during LLH was 335.68±99.869 mL and the rates of transfusion and conversion to laparotomy were 13.5%and 0%,respectively.The overall incidence of complications throughout the follow-up(median of 18 months;range 1-36 months)was 21.6%.No mortality or severe complications(level IV)were reported.CONCLUSION LLH has the potential to become a novel,standardized approach that can effectively,safely,and simply expose the middle hepatic vein and meet the requirements of precision surgery.

Which approach of total hip arthroplasty is the best efficacy and least complication?

BACKGROUND Total hip arthroplasty is as an effective intervention to relieve pain and improve hip function.Approaches of the hip have been exhaustively explored about pros and cons.The efficacy and the complications of hip approaches remains inconclusive.This study conducted an umbrella review to systematically appraise previous meta-analysis(MAs)including conventional posterior approach(PA),and minimally invasive surgeries as the lateral approach(LA),direct anterior approach(DAA),2-incisions method,mini-lateral approach and the newest technique direct superior approach(DSA)or supercapsular percutaneouslyassisted total hip(SuperPath).AIM To compare the efficacy and complications of hip approaches that have been published in all MAs and randomized controlled trials(RCTs).METHODS MAs were identified from MEDLINE and Scopus from inception until 2023.RCTs were then updated from the latest MA to September 2023.This study included studies which compared hip approaches and reported at least one outcome such as Harris Hip Score(HHS),dislocation,intra-operative fracture,wound compliData were independently selected,extracted and assessed by two reviewers.Network MA and cluster rank and surface under the cumulative ranking curve(SUCRA)were estimated for treatment efficacy and safety.RESULTS Finally,twenty-eight MAs(40 RCTs),and 13 RCTs were retrieved.In total 47 RCTs were included for reanalysis.The results of corrected covered area showed high degree(13.80%).Among 47 RCTs,most of the studies were low risk of bias in part of random process and outcome reporting,while other domains were medium to high risk of bias.DAA significantly provided higher HHS at three months than PA[pooled unstandardized mean difference(USMD):3.49,95%confidence interval(CI):0.98,6.00 with SUCRA:85.9],followed by DSA/SuperPath(USMD:1.57,95%CI:-1.55,4.69 with SUCRA:57.6).All approaches had indifferent dislocation and intraoperative fracture rates.SUCRA comparing early functional outcome and composite complications(dislocation,intra-operative fracture,wound complication,and nerve injury)found DAA was the best approach followed by DSA/SuperPath.CONCLUSION DSA/SuperPath had better earlier functional outcome than PA,but still could not overcome the result of DAA.This technique might be the other preferred option with acceptable complications.

Novel fabrication techniques for ultra-thin silicon based flexible electronics

Flexible electronics offer a multitude of advantages,such as flexibility,lightweight property,portability,and high durability.These unique properties allow for seamless applications to curved and soft surfaces,leading to extensive utilization across a wide range of fields in consumer electronics.These applications,for example,span integrated circuits,solar cells,batteries,wearable devices,bio-implants,soft robotics,and biomimetic applications.Recently,flexible electronic devices have been developed using a variety of materials such as organic,carbon-based,and inorganic semiconducting materials.Silicon(Si)owing to its mature fabrication process,excellent electrical,optical,thermal properties,and cost efficiency,remains a compelling material choice for flexible electronics.Consequently,the research on ultra-thin Si in the context of flexible electronics is studied rigorously nowadays.The thinning of Si is crucially important for flexible electronics as it reduces its bending stiffness and the resultant bending strain,thereby enhancing flexibility while preserving its exceptional properties.This review provides a comprehensive overview of the recent efforts in the fabrication techniques for forming ultra-thin Si using top-down and bottom-up approaches and explores their utilization in flexible electronics and their applications.

Modelling Foot and Mouth Disease in the Context of Active Immigrants

This study employs mathematical modeling to analyze the impact of active immigrants on Foot and Mouth Disease (FMD) transmission dynamics. We calculate the reproduction number (R0) using the next-generation matrix approach. Applying the Routh-Hurwitz Criterion, we establish that the Disease-Free Equilibrium (DFE) point achieves local asymptotic stability when R0 α1 and α2) are closely associated with reduced susceptibility in animal populations, underscoring the link between immigrants and susceptibility. Furthermore, our findings emphasize the interplay of disease introduction with population response and adaptation, particularly involving incoming infectious immigrants. Swift interventions are vital due to the limited potential for disease establishment and rapid susceptibility decline. This study offers crucial insights into the complexities of FMD transmission with active immigrants, informing effective disease management strategies.

Neomicrocoleus gen.nov.(Microcoleaceae,Oscillatoriales),a novel cyanobacterial genus from benthic mats in a water channel

A new filamentous cyanobacterial strain(CHAB 4127)was successfully isolated from the algal mat during the field investigation of the open channel from Luanhe River to Tianjin,China.The polyphasic approach combining morphological,ultrastructural,ecological,and molecular features was used to characterize this studied strain.The strain is morphologically similar to the Microcoleus-like cyanobacterial taxa under light microscopy,and the radial arrangement of thylakoids is also consistent with that of Microcoleus-like groups.The phylogenetic position of CHAB 4127 based on 16S rRNA gene sequences,is shown to be clearly clustered into an independent clade with the newly established genus Microcoleusiopsis.The maximum similarity of 16S r RNA gene of the studied strain with other existing related cyanobacterial taxa is 93.97%,and the ITS secondary structures is also obviously different from other members of Microcoleaceae.Based on all the above evidence,we proposed the establishment of this novel cyanobacterial genus as Neomicrocoleus,with its type species,Neomicrocoleus tianjinensis.

Mode Multiplication of Cylindrical Vector Beam Using Raytracing Control

Cylindrical vector beams(CVBs)hold significant promise in mode division multiplexing communication owing to their inherent vector mode orthogonality.However,existing studies for facilitating CVB channel processing are confined to mode shift conversions due to their reliance on spin-dependent helical modulations,overlooking the pursuit of mode multiplication conversion.This challenge lies in the multiplicative operation upon inhomogeneous vector mode manipulation,which is expected to advance versatile CVB channel switching and routing.Here,we tackle this gap by introducing a raytracing control strategy that conformally maps the light rays of CVB from the whole annulus distribution to an annular sector counterpart.Incorporated with the multifold conformal annulus-sector mappings and polarization-insensitive phase modulations,this approach facilitates the parallel transformation of input CVB into multiple complementary components,enabling the mode multiplication conversion with protected vector structure.Serving as a demonstration,we experimentally implemented the multiplicative operation of four CVB modes with the multiplier factors of N=+2 and N=−3,achieving the converted mode purities over 94.24%and 88.37%.Subsequently,200 Gbit/s quadrature phase shift keying signals were successfully transmitted upon multiplicative switching of four CVB channels,with the bit-error-rate approaching 1×10^(−6).These results underscore our strategy’s efficacy in CVB mode multiplication,which may open promising prospects for its advanced applications.

Thermodynamic model for deoxidation of liquid steel considering strong metal-oxygen interaction in the quasichemical model framework

Herein,a thermodynamic model aimed at describing deoxidation equilibria in liquid steel was developed.The model provides explicit forms of the activity coefficient of solutes in liquid steel,eliminating the need for the minimization of internal Gibbs energy preliminarily when solving deoxidation equilibria.The elimination of internal Gibbs energy minimization is particularly advantageous during the coupling of deoxidation equilibrium calculations with computationally intensive approaches,such as computational fluid dynamics.The model enables efficient calculations through direct embedment of the explicit forms of activity coefficient in the computing code.The proposed thermodynamic model was developed using a quasichemical approach with two key approximations:random mixing of metallic elements(Fe and oxidizing metal) and strong nonrandom pairing of metal and oxygen as nearest neighbors.Through these approximations,the quasichemical approach yielded the activity coefficients of solutes as explicit functions of composition and temperature without requiring the minimization of internal Gibbs energy or the coupling of separate programs.The model was successfully applied in the calculation of deoxidation equilibria of various elements(Al,B,C,Ca,Ce,Cr,La,Mg,Mn,Nb,Si,Ti,V,and Zr).The limitations of the model arising from these assumptions were also discussed.

Minimalistic approach to left atrial appendage occlusion guided by cardiac computed tomography angiography

OBJECTIVE To assess the feasibility and safety of the minimalistic approach to left atrial appendage occlusion(LAAO) guided by cardiac computed tomography angiography(CCTA).METHODS Ninety consecutive patients who underwent LAAO, with or without CCTA-guided, were matched(1:2). Each step of the LAAO procedure in the computed tomography(CT) guidance group(CT group) was directed by preprocedural CT planning. In the control group, LAAO was performed using the standard method. All patients were followed up for 12 months, and device surveillance was conducted using CCTA.RESULTS A total of 90 patients were included in the analysis, with 30 patients in the CT group and 60 matched patients in the control group. All patients were successfully implanted with Watchman devices. The mean ages for the CT group and the control group were 70.0 ± 9.4 years and 68.4 ± 11.9 years(P = 0.52), respectively. The procedure duration(45.6 ± 10.7 min vs. 58.8 ± 13.0 min,P < 0.001) and hospital stay(7.5 ± 2.4 day vs. 9.6 ± 2.8 day, P = 0.001) in the CT group was significantly shorter compared to the control group. However, the total radiation dose was higher in the CT group compared to the control group(904.9 ± 348.0 m Gy vs.711.9 ± 211.2 m Gy, P = 0.002). There were no significant differences in periprocedural pericardial effusion(3.3% vs. 6.3%, P = 0.8) between the two groups. The rate of postprocedural adverse events(13.3% vs. 18.3%, P = 0.55) were comparable between both groups at 12 months follow-up.CONCLUSIONS CCTA is capable of detailed LAAO procedure planning. Minimalistic LAAO with preprocedural CCTA planning was feasible and safe, with shortened procedure time and acceptable increased radiation and contras consumption. For patients with contraindications to general anesthesia and/or transesophageal echocardiography, this promising method may be an alternative to conventional LAAO.