Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Harnessing the power of pericytes and hypoxia-inducible factor-1 to modulate stroke outcome

The human brain has exceedingly high metabolic demands.The cerebral vasculature has the critical task of providing sufficient blood supply to meet this demand.The sudden interruption of blood flow to the brain,as observed during ischemic stroke,results in acute neurological injury with devastating consequences-a high rate of adult disability and death.Ischemic stroke is thus a vascular disorder with a dramatic neurological impact.There is an urgent need for more effective disease management to combat stroke as current treatment paradigms,focusing on vascular recanalization and neuroprotection,have only limited clinical success.Since accumulating data suggests successful long-term neuroprotection is unlikely to be achievable without a functional microvascular network,strategies that reduce endothelial dysfunction could be indispensable.Encouragingly,very recent evidence highlighted herein suggests protecting the humble pericyte may be a new approach to reaching this goal.

Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

Sustainable Intensification and Large-scale Operation of Cultivated Land Use at the Farmers’ Scale:A Case Study of Shandong Province,China

Sustainable intensification of cultivated land use(SICLU) and large-scale operations(LSO) are widely acknowledged strategies for enhancing agricultural performance.However,the existing literature has faced challenges in precisely defining SICLU and constructing comprehensive indicators,which has hindered the exploration of factors influencing LSO within the SICLU framework.To address this gap,we integrated self-efficacy theory into the design of an index framework for evaluating SICLU.We subsequently employed econometric models to analyze the significant factors that impact LSO.Our findings reveal that SICLU can be divided into four key dimensions:intensive management,efficient output,resource conservation,and ecological environment optimization.Furthermore,it is crucial to incorporate belief-based cognitive factors into the index system,as farmers’ understanding of fertilizer and pesticide application significantly influences their willingness to engage in LSO.Moreover,we identify grain market turnover as the most influential factor in promoting LSO,with single-factor contribution rates reaching 70.9% for cultivated land transfer willingness and 62.5% for the total planting areas.Interestingly,unlike irrigation and agricultural machinery inputs,increased labor inputs correspond to larger planting areas for farmers.This trend may be attributed to reduced labor availability because of rural labor migration,whereas the reduction in irrigation and agricultural input is contingent on innovations in production practices and the transfer of cultivated land management rights.Importantly,SICLU dynamically influences LSO,with each index related to SICLU having an optimal range that fosters LSO.These insights offer valuable guidance for policymakers,emphasizing farmers as their central focus,with the adjustment of input and output factors as a means to achieve LSO as the ultimate goal.In conclusion,we propose research avenues for further enriching the SICLU framework to ensure that it aligns with the specific characteristics of regional agricultural development.

Femoral Access with Ultrasound-Guided Puncture and Z-Stitch Hemostasis for Adults with Congenital Heart Diseases Undergoing Electrophysiological Procedures

Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)procedures.We sought to evaluate the safety and efficacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP procedures.Methods and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and analyzed.During the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound guidance.At the end of the procedure,a single Z-stitch was performed at the puncture site.We eval-uated the incidence of in-hospital complications associated with femoral access puncture in this population.Among 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP procedures.The median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousfistula,venous or arterial thrombosis.Conclusion:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.

Advances in non-invasive imaging of proteinopathies in animal models of neurodegenerative diseases

Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific pattern.Earlier studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.

Routine utilization of machine perfusion in liver transplantation:Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation.Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses,providing the highest available evidence on the protective effect of machine perfusion(MP)over static cold storage in liver transplantation(LT).Based on a protective effect with less complications and improved graft survival,the field has seen a paradigm shift in organ preservation.This editorial focuses on the role of MP in LT and how it could become the new“gold standard”.Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Restoration of GABA_(B) receptor expression in cerebral ischemia:a promising novel neuroprotective strategy

Although stroke is a major global health problem, a pharmacological treatment to inhibit ongoing neuronal death in patients is still lacking. In cerebral ischemia, the prevailing form of stroke, severely reduced blood supply by obstruction of blood vessels deprives neurons from oxygen and glucose, eventually leading to metabolic derailment and death of neurons in the affected brain area.

Neural Network-Based Limiter with Transfer Learning

Recent works have shown that neural networks are promising parameter-free limiters for a variety of numerical schemes(Morgan et al.in A machine learning approach for detect-ing shocks with high-order hydrodynamic methods.et al.in J Comput Phys 367:166-191.,2018;Veiga et al.in European Conference on Computational Mechanics andⅦEuropean Conference on Computational Fluid Dynamics,vol.1,pp.2525-2550.ECCM.,2018).Following this trend,we train a neural network to serve as a shock-indicator function using simulation data from a Runge-Kutta discontinuous Galer-kin(RKDG)method and a modal high-order limiter(Krivodonova in J Comput Phys 226:879-896.,2007).With this methodology,we obtain one-and two-dimensional black-box shock-indicators which are then coupled to a standard limiter.Furthermore,we describe a strategy to transfer the shock-indicator to a residual distribution(RD)scheme without the need for a full training cycle and large data-set,by finding a mapping between the solution feature spaces from an RD scheme to an RKDG scheme,both in one-and two-dimensional problems,and on Cartesian and unstruc-tured meshes.We report on the quality of the numerical solutions when using the neural network shock-indicator coupled to a limiter,comparing its performance to traditional lim-iters,for both RKDG and RD schemes.

Stationarity Preservation Properties of the Active Flux Scheme on Cartesian Grids

Hyperbolic systems of conservation laws in multiple spatial dimensions display features absent in the one-dimensional case,such as involutions and non-trivial stationary states.These features need to be captured by numerical methods without excessive grid refine-ment.The active flux method is an extension of the finite volume scheme with additional point values distributed along the cell boundary.For the equations of linear acoustics,an exact evolution operator can be used for the update of these point values.It incorporates all multi-dimensional information.The active flux method is stationarity preserving,i.e.,it discretizes all the stationary states of the PDE.This paper demonstrates the experimental evidence for the discrete stationary states of the active flux method and shows the evolution of setups towards a discrete stationary state.

Extracellular matrix remodelling in dental pulp tissue of carious human teeth through the prism of single-cell RNA sequencing

Carious lesions are bacteria-caused destructions of the mineralised dental tissues,marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue.While major molecular players in tooth decay have been uncovered during the past years,a detailed map of the molecular and cellular landscape of the diseased pulp is still missing.In this study we used single-cell RNA sequencing analysis,supplemented with immunostaining,to generate a comprehensive single-cell atlas of the pulp of carious human teeth.Our data demonstrated modifications in the various cell clusters within the pulp of carious teeth,such as immune cells,mesenchymal stem cells(MSC)and fibroblasts,when compared to the pulp of healthy human teeth.Active immune response in the carious pulp tissue is accompanied by specific changes in the fibroblast and MSC clusters.These changes include the upregulation of genes encoding extracellular matrix(ECM)components,including COL1A1 and Fibronectin(FN1),and the enrichment of the fibroblast cluster with myofibroblasts.The incremental changes in the ECM composition of carious pulp tissues were further confirmed by immunostaining analyses.Assessment of the Fibronectin fibres under mechanical strain conditions showed a significant tension reduction in carious pulp tissues,compared to the healthy ones.The present data demonstrate molecular,cellular and biomechanical alterations in the pulp of human carious teeth,indicative of extensive ECM remodelling,reminiscent of fibrosis observed in other organs.This comprehensive atlas of carious human teeth can facilitate future studies of dental pathologies and enable comparative analyses across diseased organs.

Axon degeneration:new actor in an old play

After an insult of white matter tracts,e.g.in the spinal cord or optic nerve,axons react in general by the activation of a tightly regulated self-destruction program.This so-called axon degeneration cascade can be triggered by various causes,including injury,toxins,and genetic defects,and is a shared pathway in many different neurological diseases(Coleman and Hoke,2020).Axonal degeneration is thought to be responsible for disease progression and accumulation of disability across many neurological conditions.The hallmark of early axonal injury is the appearance of local spheroid formations along the axon,often referred to as a“pearl-on-string”pattern or axonal beading or swelling.Although this striking shape change has been observed after various types of injury,such as mechanical,chemical,or inflammatory stimuli,we know little about its exact mechanism and its immediate impact on axonal functionality.In this perspective,we would like to contrast the classical calcium-dependent form of axonal degeneration with a recently described form of a calcium-independent mechanism underlying axonal beading.

Built‑In Electric Field‑Driven Ultrahigh‑Rate K‑Ion Storage via Heterostructure Engineering of Dual Tellurides Integrated with Ti_(3)C_(2)T_(x)MXene

Exploiting high-rate anode materials with fast K+diffusion is intriguing for the development of advanced potassium-ion batteries(KIBs)but remains unrealized.Here,heterostructure engineering is proposed to construct the dual transition metal tellurides(CoTe_(2)/ZnTe),which are anchored onto two-dimensional(2D)Ti_(3)C_(2)T_(x)MXene nanosheets.Various theoretical modeling and experimental findings reveal that heterostructure engineering can regulate the electronic structures of CoTe_(2)/ZnTe interfaces,improving K+diffusion and adsorption.In addition,the different work functions between CoTe_(2)/ZnTe induce a robust built-in electric field at the CoTe_(2)/ZnTe interface,providing a strong driving force to facilitate charge transport.Moreover,the conductive and elastic Ti_(3)C_(2)T_(x)can effectively promote electrode conductivity and alleviate the volume change of CoTe_(2)/ZnTe heterostructures upon cycling.Owing to these merits,the resulting CoTe_(2)/ZnTe/Ti_(3)C_(2)T_(x)(CZT)exhibit excellent rate capability(137.0 mAh g^(-1)at 10 A g^(-1))and cycling stability(175.3 mAh g^(-1)after 4000 cycles at 3.0 A g^(-1),with a high capacity retention of 89.4%).More impressively,the CZT-based full cells demonstrate high energy density(220.2 Wh kg^(-1))and power density(837.2 W kg^(-1)).This work provides a general and effective strategy by integrating heterostructure engineering and 2D material nanocompositing for designing advanced high-rate anode materials for next-generation KIBs.

Analysis of the SBP-SAT Stabilization for Finite Element Methods Part Ⅱ:Entropy Stability

In the hyperbolic research community,there exists the strong belief that a continuous Galerkin scheme is notoriously unstable and additional stabilization terms have to be added to guarantee stability.In the first part of the series[6],the application of simultaneous approximation terms for linear problems is investigated where the boundary conditions are imposed weakly.By applying this technique,the authors demonstrate that a pure continu-ous Galerkin scheme is indeed linearly stable if the boundary conditions are imposed in the correct way.In this work,we extend this investigation to the nonlinear case and focus on entropy conservation.By switching to entropy variables,we provide an estimation of the boundary operators also for nonlinear problems,that guarantee conservation.In numerical simulations,we verify our theoretical analysis.

Early Cardiac Catheterizations within 30 Days Post Congenital Heart Surgery in Children

Background:This study set out to assess the indications,feasibility,safety,and outcome of early cardiac catheterizations(CC)within 30 days after congenital heart surgery(CHS)in children.Methods and Results:This is a retrospective,single-center case review study of all CC within 30 days after CHS between 1/2010-12/2020.A total of 317(138 diagnostic,179 interventional)CC were performed in 245 patients at a median of 4 days(IQR 13)after CHS.The median age was 3 months(IQR 6),and body weight was 5 kg(IQR 4).A total of 194(61.2%)CC were performed in patients with univentricular hearts.CC revealed significant pathologies leading to early redo-surgery in 37 patients(12%).The transcatheter interventions primarily were needed in patients after cavo-pulmonary connection(n=69%,21.8%),right ventricle to pulmonary artery conduit(n=39%,12.3%),and Norwood-I surgery(n=34%,10.7%)presenting with hypoxemia,prolonged postoperative course,and suspected arterial stenosis on echocardiography.The clinical impact of an early postoperative transcatheter intervention for the following clinical course was high in most cases.There were nine(2.8%)major and 20(6.3%)minor intra-procedural complications.Risk factor analysis revealed no difference for the occurrence of complications for patients’age,weight,and time from initial CHS,underlying uni-vs.biventricular heart disease,or ECMO.Conclusion:Early CC within 30 days after CHS in children can be performed safely with a high diagnostic and therapeutic value.The rate of complications is low,while the therapeutic consequence is relevant.

Histological and magnetic resonance imaging assessment of Liqoseal in a spinal in vivo pig model

Background:Liqoseal (Polyganics,B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage.It has been extensively tested preclinically and CE (Conformite Européenne) approved for human use after a first cranial in-human study.However,the safety of Liqoseal for spinal application is still unknown.The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics.Methods:Eight female Dutch Landrace pigs underwent laminectomy,durotomy with standard suturing and Liqoseal application.Three control animals underwent the same procedure without sealant application.The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model.Results:Similar foreign body reactions were observed in spinal and cranial dura.The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first3 days,changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7.Mean Liqoseal plus dura thickness reached a maximum of 1.2mm(range 0.7-2.0mm) at day 7.Conclusion:The spinal dural histological reaction to Liqoseal during the first 7days was similar to the cranial dural reaction.Liqoseal did not swell significantly in both application areas over time.Given the current lack of a safe and effective dural sealant for spinal application,we propose that an in-human safety study of Liqoseal is the logical next step.

大数据资源规划研究框架的构建

大数据资源规划是组织和国家管理大数据资源初期解决"如何开始,从哪里开始"的关键环节。基于对国内外大数据资源规划研究进展的系统梳理,本文从实践视角和理论视角对大数据资源规划研究进行了科学定位,并结合战略规划理论与信息资源规划理论,从宏观、中观和微观三个层面构建了大数据资源规划的研究框架。通过研究,得出如下结论:(1)大数据应用尚处在起步阶段,在此阶段研究大数据资源规划具有现实意义;(2)国内外学者已经着手研究大数据资源管理与规划,但研究视角有所差异,研究内容尚未系统化;(3)大数据资源、大数据资源管理需要从广义和狭义明晰地界定;(4)战略规划与信息资源规划理论都经历一个从微观到宏观的发展历程,为大数据资源规划研究提供了理论参考;(5)需要从国家、领域、组织三个视角构建大数据资源规划的研究框架,探索其研究的共性与个性问题。

含生物素的双功能螯合剂合成及[^(99)Tc^m(CO)_3(H_2O)_3]^+标记

设计合成了一种新的用于生物素偶联的双功能螯合剂N--α(2-皮考基)-N-ε-D-生物素基-L-赖氨酸甲酯(PLB),并完成其Re(CO)3-PLB配合物的合成及化学结构的表征。[99Tcm(CO)3(H2O)3]+的标记条件研究表明,PLB配体浓度在10μmol/L以上,pH在正常生理值7.4左右,于95℃加热30 min,标记物的放化纯度大于95%,比活度达37~55.5 TBq/mmol。

创伤经历者的网络自助干预程序的试用研究

目的:检验网络自助干预程序的使用价值,了解创伤症状水平、社会认可度、创伤暴露态度与程序使用的关系,为未来的网络干预研究提供参考。方法:通过网络广告征集428名创伤经历者,其中103人成为被试,随机分入干预组和等待组,进行1个月的网络自助干预。等待组在后测之后进行延迟自助干预。对两组被试在干预前的流失率、使用干预程序的程度(访问天数、访问网页数)和后续流失率进行考察。用创伤后压力诊断量表(PDS)、创伤暴露问卷(DTQ)和社会认可问卷(SAQ)进行测量。结果:干预开始前,被试流失率为40.8%。与使用网站的被试相比,干预前流失的被试在DTQ的谈论冲动维度上得分更高[(2.1±1.2)vs.(1.5±1.0),P<0.05],并且女性所占比例更高(86%vs.69%,P=0.050)。在61名使用网站的被试中,访问网站的人数第1周为61名(100%),第2周为19名(31%),之后人数较平稳;在1个月内,51名(84%)被试访问网站的天数为≤5天,4名(7%)被试访问天数>10天(最大值为12天);在网页总数为118的网站上,被试访问的网页数平均值为(81.3±77.1),其中18名(30%)被试(重复)访问超过100个网页(最大值为295)。回归分析显示,被试访问网站的天数与SAQ的家庭不认可维度得分正相关(β=0.31,P<0.05);访问网页数与SAQ的一般不认可维度得分正相关(β=0.31,P<0.05)。结论:创伤经历者的谈论冲动可能是其选择网络自助干预的一个因素;在开始使用干预程序后,使用者可能在少数几次登录中重复阅读部分或全部内容,从家庭中、社会上感受到的不认可态度可能是其坚持使用干预程序的一个促进因素。

云南白马雪山自然保护区猕猴和滇金丝猴的生态位分离(英文)

原则上,食叶的滇金丝猴(Rhinopithecus bieti)和杂食的猕猴(Macaca mulatta)是可以同地共栖的,但这两种灵长类究竟是如何同地共存却一直是一个鲜见涉足的问题。该文初步通过分析它们的食性和生境需求来阐明两者共存的可能性。在猕猴取食约22种植物中,有16种也是滇金丝猴的取食对象。两种灵长类都显示出喜食果实。人们尚未发现滇金丝猴涉足人类作物等相关资源,但发现猕猴经常侵食庄稼。这与其生活海拔不同有关:滇金丝猴一般生活在平均海拔为3218m的山林中,而猕猴活动在平均海拔为2995m的林地。猕猴也会涉足牧场,而滇金丝猴回避这种场地。对于这两个种,混合的落叶阔叶/针叶林是最频繁使用的森林类型;滇金丝猴很少进入常绿阔叶林(青冈属群落,利用率仅3%),而猕猴相对进入这类林型的机会远比滇金丝猴高(36%)。两个物种的群体间常相互远离(2.4km)。当其相遇时,常是猕猴主动回避。上述结果提示滇金丝猴和猕猴是通过大生境分化利用和空间避让来共存的。尽管不同的生境利用策略一定程度上会反映种间竞争的存在,但这种不同更可能反映着它们不同的生理/生态需求。