Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Enhanced anomalous Hall effect in kagome magnet YbMn_(6)Sn_(6)with intermediate-valence ytterbium

We report on the magnetization and anomalous Hall effect(AHE)in the high-quality single crystals of the kagome magnet YbMn_(6)Sn_(6),where the spins of the Mn atoms in the kagome lattice order ferromagnetically and the intermediate-valence Yb atoms are nonmagnetic.The intrinsic mechanism plays a crucial role in the AHE,leading to an enhanced anomalous Hall conductivity(AHC)compared with the other rare-earth RMn_(6)Sn_(6)compounds.Our band structure calculation reveals a strong hybridization between the 4f electrons of Yb and conduction electrons.

Core-shell mesoporous carbon hollow spheres as Se hosts for advanced Al-Se batteries

Incorporating a selenium(Se)positive electrode into aluminum(Al)-ion batteries is an effective strategy for improving the overall battery performance.However,the cycling stability of Se positive electrodes has challenges due to the dissolution of intermediate reaction products.In this work,we aim to harness the advantages of Se while reducing its limitations by preparing a core-shell mesoporous carbon hollow sphere with a titanium nitride(C@TiN)host to load 63.9wt%Se as the positive electrode material for Al-Se batteries.Using the physical and chemical confinement offered by the hollow mesoporous carbon and TiN,the obtained core-shell mesoporous carbon hollow spheres coated with Se(Se@C@TiN)display superior utilization of the active material and remarkable cycling stability.As a result,Al-Se batteries equipped with the as-prepared Se@C@TiN composite positive electrodes show an initial discharge specific capacity of 377 mAh·g^(-1)at a current density of 1000 mA·g^(-1)while maintaining a discharge specific capacity of 86.0 mAh·g^(-1)over 200 cycles.This improved cycling performance is ascribed to the high electrical conductivity of the core-shell mesoporous carbon hollow spheres and the unique three-dimensional hierarchical architecture of Se@C@TiN.

Regulating^(*)COOH intermediate via amino alkylation engineering for exceptionally effective photocatalytic CO_(2) reduction

Photocatalytic reduction of CO_(2) into fuel represents a promising approach for achieving carbon neutrality,while realizing high selectivity in this process is challenging due to uncontrollable reaction intermediate and retarded desorption of target products.Engineering the interface microenvironment of catalysts has been proposed as a strategy to exert a significant influence on reaction outcomes,yet it remains a significant challenge.In this study,amino alkylation was successfully integrated into the melem unit of polymeric carbon nitrides(PCN),which could efficiently drive the photocatalytic CO_(2) reduction.Experimental characterization and theoretical calculations revealed that the introduction of amino alkylation lowers the energy barrier for CO_(2) reduction into^(*)COOH intermediate,transforming the adsorption of^(*)COOH intermediate from the endothermic to an exothermic process.Notably,the as-prepared materials demonstrated outstanding performance in photocatalytic CO_(2) reduction,yielding CO_(2)at a rate of 152.8μmol h^(-1) with a high selectivity of 95.4%and a quantum efficiency of 6.6%.

The study of intelligent algorithm in particle identification of heavy-ion collisions at low and intermediate energies

Traditional particle identification methods face timeconsuming,experience-dependent,and poor repeatability challenges in heavy-ion collisions at low and intermediate energies.Researchers urgently need solutions to the dilemma of traditional particle identification methods.This study explores the possibility of applying intelligent learning algorithms to the particle identification of heavy-ion collisions at low and intermediate energies.Multiple intelligent algorithms,including XgBoost and TabNet,were selected to test datasets from the neutron ion multi-detector for reaction-oriented dynamics(NIMROD-ISiS)and Geant4 simulation.Tree-based machine learning algorithms and deep learning algorithms e.g.TabNet show excellent performance and generalization ability.Adding additional data features besides energy deposition can improve the algorithm’s performance when the data distribution is nonuniform.Intelligent learning algorithms can be applied to solve the particle identification problem in heavy-ion collisions at low and intermediate energies.

Interface optimization and defects suppression via Na F introduction enable efficient flexible Sb_(2)Se_(3) thin-film solar cells

Sb_(2)Se_(3) with unique one-dimensional(1D) crystal structure exhibits exceptional deformation tolerance,demonstrating great application potential in flexible devices.However,the power conversion efficiency(PCE) of flexible Sb_(2)Se_(3) photovoltaic devices is temporarily limited by the complicated intrinsic defects and the undesirable contact interfaces.Herein,a high-quality Sb_(2)Se_(3) absorber layer with large crystal grains and benign [hkl] growth orientation can be first prepared on a Mo foil substrate.Then NaF intermediate layer is introduced between Mo and Sb_(2)Se_(3),which can further optimize the growth of Sb_(2)Se_(3)thin film.Moreover,positive Na ion diffusion enables it to dramatically lower barrier height at the back contact interface and passivate harmful defects at both bulk and heterojunction.As a result,the champion substrate structured Mo-foil/Mo/NaF/Sb_(2)Se_(3)/CdS/ITO/Ag flexible thin-film solar cell delivers an obviously higher efficiency of 8.03% and a record open-circuit voltage(V_(OC)) of 0.492 V.This flexible Sb_(2)Se_(3) device also exhibits excellent stability and flexibility to stand large bending radius and multiple bending times,as well as superior weak light photo-response with derived efficiency of 12.60%.This work presents an effective strategy to enhance the flexible Sb_(2)Se_(3) device performance and expand its potential photovoltaic applications.

Freshening of the Intermediate Waters in the Northern South China Sea over the Past Six Decades

The properties of salinity in the South China Sea(SCS),a significant marginal sea connecting the Pacific and Indian Oceans,are greatly influenced by the transport of fresh water flux between the two oceans.However,the long-term changes in the intermediate water in the SCS have not been thoroughly studied due to limited data,particularly in relation to its thermodynamic variations.This study utilized reanalysis data products to identify a 60-year trend of freshening in the intermediate waters of the northern South China Sea(NSCS),accompanied by an expansion of low-salinity water.The study also constructed salinity budget terms,including advection and entrainment processes,and conducted an analysis of the salinity budget to understand the impacts of external and internal dynamic processes on the freshening trend of the intermediate water in the NSCS.The analysis revealed that the freshening in the northwest Pacific Ocean and the intensification of intrusion through the Luzon Strait at intermediate levels are the primary drivers of the salinity changes in the NSCS.Additionally,a weakened trend in the intensity of vertical entrainment also contributes to the freshening in the NSCS.This study offers new insights into the understanding of regional deep sea changes in response to variations in both thermodynamics and oceanic dynamic processes.

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data:A case report

BACKGROUND Invasive functional evaluation by fractional flow reserve(FFR)is considered as a gold standard for the evaluation of intermediate coronary stenosis.However,in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing.CASE SUMMARY We present a case of 55-year-old male diabetic patient who was admitted for chest pain.Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent.Patient undergone invasive functional testing of intermediate lesion with preserved FFR(0.88),low coronary flow reserve(1.2)and very high index of microvascular resistance(84).Due to discrepancy in invasive functional parameters,intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma.Because of the preserved FFR and no signs of vulnerable plaque,the interventional procedure was deferred and the patient continued with optimal medications.CONCLUSION Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

Intermediality in the Contemporary Brazilian Literature

Literature adapts following the changes of its objects,as do all arts.However,while fictional characters and context can be said to have equivalents in people and society,the same cannot be said about the literature form itself.Especially with the advent of the internet,this transformations in literature seem more visible:it has become spread in the cloud,surpassing its boundaries and mixing with the profusion of voices of the cyberspace.Intermediality,in addition to its theories about the intermedial phenomena,has become a methodology or even a pathway to understand arts.This paper presents part of an extensive analysis of a corpus formed by contemporary Brazilian literature,in order to describe different manifestations on how the"mediatized society"appears through the literature forms,from the Media Culture to today.

Spectral Soundscapes in Elfriede Jelinek’s Post-Holocaust Novel The Children of the Dead and Its 2019 Film Adaptation

How should we approach Die Kinder der Toten by the Austrian Nobel Prize winner Elfriede Jelinek today?And how does the 2019 film adaptation by the Nature Theatre of Oklahoma change the text’s reception through focus on intermedial and intertextual elements?So far,the most insightful reviews have centered on the conceptual,contextual and textual-and thus also political aspects of this work.By focusing on intertextual and intermedial components,I hope to illustrate a few aspects of the novel that have yet to be analyzed in the scholarship on Jelinek.Drawing on Derrida’s Specters of Marx and on elements of sound studies,literature studies,and film studies,I hope to demonstrate how sound can have a significant spectral presence that connects with other literary texts and media,different world regions in the past,the present and the future.

Experimental study on failure characteristics of single-sided unloading rock under different intermediate principal stress conditions

Investigation of unloading rock failure under differentσ_(2)facilitates the control mechanism of excavation surrounding rock.This study focused on single-sided unloading tests of granite specimens under true triaxial conditions.The strength and failure characteristics were studied with micro-camera and acoustic emission(AE)monitoring.Furthermore,the choice of test path and the effect ofσ_(2)on fracture of unloading rock were discussed.Results show that the increasedσ_(2)can strengthen the stability of single-sided unloading rock.After unloading,the rock’s free surface underwent five phases,namely,inoculation,particle ejection,buckling rupture,stable failure,and unstable rockburst phases.Moreover,atσ_(2)≤30 MPa,the b value shows the following variation tendency:rising,dropping,significant fluctuation,and dropping,with dispersed damages signal.Atσ_(2)≥40 MPa,the tendency shows:a rise,a decrease,a slight fluctuation,and final drop,with concentrated damages signal.After unloading,AE energy is mainly concentrated in the micro-energy range.With the increasedσ_(2),the micro-energy ratio rises.In contrast,low,medium and large energy ratios drop gradually.The increased tensile fractures and decreased shear fractures indicate that the failure mode of the unloading rock gradually changes from tensile-shear mode to tensile-split one.The fractional dimension of the rock fragments first increases and then decreases with an inflection point at 20 MPa.The distribution of SIF on the planes changes asσ_(2)increases,resulting in strengthening and then weakening of the rock bearing capacity.

Effects of intermediate stress on deep rock strainbursts under true triaxial stresses

The effect of intermediate stress(in situ tunnel axial)on a strainburst is studied with a threedimensional(3D)bonded block distinct element method(DEM).A series of simulations of strainbursts under true triaxial in situ stress conditions(i.e.high tangential stress,moderate intermediate stress and low radial stress)of near-boundary rock masses are performed.Compared with the experimental results,the DEM model is able to capture the stress-strain response,failure pattern and energy balance of strainbursts.The fracturing processes of strainbursts are also numerically reproduced.Numerical results show that,as the intermediate stress increases:(1)The peak strain of strainbursts increases,the yield stress increases,the rock strength increases linearly,and the ratio of yield stress to rock strength decreases,indicating that the precursory information on strainbursts is enhanced;(2)Tensile and shear cracks increase significantly,and slabbing and bending of rock plates are more pronounced;and(3)The stored elastic strain energy and dissipated energy increase linearly,whereas the kinetic energy of the ejected rock fragments increases approximately exponentially,implying an increase in strainburst intensity.By comparing the experimental and numerical results,the effect of intermediate stress on the rock strength of strainbursts is discussed in order to address three key issues.Then,the Mogi criterion is applied to construct new strength criteria for strainbursts by converting the one-face free true triaxial stress state of a strainburst to its equivalent true triaxial stress state.In summary,the effect of intermediate stress on strainbursts is a double-edged sword that can enhance the rock strength and the precursory information of a strainburst,but also increase its intensity.

Unveil the Redox Evolution of Ore-forming Fluids using Sulfur Isotope:A Case Study of the Zhengguang Intermediate Sulfidation Epithermal Au-Zn Deposit,NE China

Oxygen fugacity(fO_(2))is a key intensity variable during the entire magmatic-hydrothermal mineralization courses.The redox state and its variations between different stages of the ore-forming fluids of intermediate sulfidation epithermal deposits are rarely deciphered due to the lack of appropriate approaches to determine fO_(2)of the fluids.Here,we reported theδ^(34)S of the sulfides from three different stages(stageⅠ,Ⅱ,Ⅲ)of Zhengguang,an Early Ordovician Au-rich intermediate sulfidation(IS)epithermal deposit,to decipher the redox evolution of the ore-forming fluids.The increasingδ^(34)S values from stageⅠpyrite(pyl,average-2.6‰)through py2(average-1.9‰)to py3(average-0.2‰)indicates a decrease of the oxygen fugacity of the ore-forming fluids.A compilation ofδ^(34)S values of sulfides from two subtypes of IS deposits(Au-rich and Ag-rich)from NE China shows that theδ^(34)S values of sulfides from Au-rich IS deposits are systematically lighter than those of Ag-rich IS Ag-Pb-Zn deposit,indicating the ore-forming fluids of the former are more oxidized than the latter.We highlight that sulfur isotopic composition of hypogene sulfides is an efficacious proxy to fingerprint the oxygen fugacity fluctuations of epithermal deposits and could potentially be used to distinguish the subtypes of IS deposits.

Mechanistic insights into the active intermediates of 2,6-diaminopyridine dinitration

Mechanistic understanding of the active intermediates of 2,6-diaminopyridine(DAP) dinitration in the concentrated nitric-sulfuric acid system is of crucial importance for the selectivity control of target product, i.e., 2,6-diamino-3,5-dinitropyridine(DADNP). The active intermediates determining the product selectivity are theoretically studied. The HSO_(4)^(-)-NO_(2)^(+) complex is proposed as the dominant active nitrating intermediate for the first time, which shows low energy barrier(i.e., 10.19 kcal·mol^(-1),1 kcal = 4.186 k J) for direct dinitration of DAP to DADNP. The formed water during the reaction results in not only the formation of less active SO_(4)^(2-)-NO_(2)^(+) complex, but also the occurance of DAP sulfonation(DAP-SO_(3)H intermediate)to facilitate the formation of mononitration byproduct. Meanwhile, the accompanied thermal effects cause the generation of undesirable pyridine-NHNO_(2) intermediate, which is difficult to be rearranged to yield DADNP, inhibiting the reaction and thus giving low DAP conversion. The insights reported here elucidates the importance of thermal effects elimination and water content control, confirmed experimentally in the batch-and micro-reaction systems.

Effects of land-use types and the exotic species,Hypochaeris radicata,on plant diversity in human-transformed landscapes of the biosphere reserve,Jeju Island,Korea

Land-use and plant invasion influence biodiversity.Understanding the effects of land-use types and invasive plants on the ecosystem is crucial for better management and the development of strategic plans for increasing biodiversity in Jeju Island,Korea,a designated Biosphere Reserve by the United Nations Education,Scientific,and Cultural Organization.The effect of the most dominant invasive exotic species,Hypochaeris radicata,on the four land-use types of Jeju Island was investigated.Plant composition,soil characteristics,and plant diversity among four land-use types(cropland,green space,neglected land,and residential)were compared.Among the land-use types,croplands had the most diverse plant composition and the highest richness in exotic and native plant species.Croplands,such as tangerine orchards,which are widely distributed throughout Jeju Island,showed the highest plant diversity because of medium intensity disturbance caused by weed removal.The relative cover of H.radicata did not differ between land-use types.However,H.radicata invasion was negatively related with plant species richness,making this invasive species a threat to the biodiversity of native herbs present in land-use areas.H.radicata adapts to areas with a broad range of soil properties and a variety of land-use types.Therefore,it is crucial to monitor land-use types and patterns of plant invasion to guide the implementation of consistent management and conservation strategies for maintaining ecosystem integrity of the transformed habitat in Jeju Island.

Wave Force on the Crown Wall of Rubble Mound Breakwaters at Intermediate Depths

Rubble mound breakwaters with a crown wall are a common coastal engineering structure.The wave force on crown walls is an important parameter for the practice engineering design.Particularly,the wave force on crown walls under intermediate depths has been studied through physical model tests and numerical simulations.In this study,a three-dimensional numerical wave flume was developed to investigate monochromatic wave interactions in a rubble mound breakwater with a crown wall.Armor blocks were modeled in detail.The Navier-Stokes equations for two-phase incompressible flows,combined with shear stress transport k-ωturbulence model and volume of fluid method for tracking the free surface,were solved.A set of laboratory experiments were performed to validate the adopted model.Subsequently,a series of numerical simulations were implemented to examine the impacts of different hydrodynamic parameters(including wave height,incident wave period,and water depth)and the berm width on the wave force of the crown wall.Finally,a comparison of the experimental results and Martin method shows that the latter method is not suitable for this experimental scope.New empirical formulas are proposed to predict the wave force on crown walls under intermediate depth.The results can provide a basis for the design of crown wall of rubble mound breakwaters at intermediate depths.

Morphology and morphometry of two hybridizing buntings at their hybrid zone in northern Iran reveal intermediate and transgressive morphotypes

The closely related Black-headed Bunting(Emberiza melanocephala,a western Palearctic lineage)and Red-headed Bunting(Emberiza bruniceps,an eastern Palearctic lineage)hybridize and replace each other south of the Caspian Sea.The parental species have distinct phenotypes and therefore morphology is useful for assessing hybridization in the contact zone.In the years of 1940 and 1977,quite a few hybrids were collected and studied morphologically.Since then,the hybrid zone appears to have expanded westwards,but there has been a time gap in the collection of morphological data.Here we reanalyze bunting specimens morphologically and compare the historical data with recent data.Morphometric and phenotypic traits from three time periods(1940,1977 and recent)were studied to assess phenotypic variation of hybrids,pattern of hybridization,and transgressive traits in the hybrid zone.Our results show that most of the birds in the hybrid zone exhibit intermediate phenotypes(both colors and morphometric characters),ranging from the pure phenotype of either of the parental species.However,hybridization has also produced novel phenotypes not seen in any of the parents.Using a canonical discriminant function analysis,the morphometric characters separated each parental species and the hybrids quite well.Our results showed morphometric intermediacy of hybrids in accordance with phenotypes.We observe a time trend in which recent hybrids are more similar to Red-headed Buntings phenotypically compared to historical samples.This pattern is likely a signature of a westward expansion of the Red-headed Bunting into the breeding range of the Black-headed Bunting.

Amorphous Sn(HPO_(4))_(2)-derived phosphorus-modified Sn/SnO_(x) core/shell catalyst for efficient CO_(2) electroreduction to formate

Simultaneously achieving high activity,selectivity and stability for electrochemical CO_(2)reduction reaction(CO_(2)RR)remains great challenges.Herein,a phosphorus-modified Sn/Sn Oxcore/shell(P-Sn/SnO_x)catalyst,derived from in situ electrochemical reduction of an amorphous Sn(HPO_(4))_(2) pre-catalyst,exhibits high CO_(2)RR performance.The total Faradaic efficiency(FE)of C_(1) products is close to 100%in a broad potential range from-0.49 to-1.02 V vs.reversible hydrogen electrode,and a total current density of 315.0 m A cm^(-2)is achieved.Moreover,the P-Sn/SnO_(x) catalyst maintains a formate FE of~90%for 120 h.Density functional theory calculations suggest that the phosphorus-modified Sn/SnO_(x) core/shell structure effectively facilitates formate production by enhancing CO_(2)adsorption and improving free energy profile of formate formation.

Hydrogen production at intermediate temperatures with proton conducting ceramic cells:Electrocatalytic activity,durability and energy efficiency

Proton conducting ceramic cells(PCCs)are an attractive emerging technology operating in the intermediate temperature range of 500 to 700℃.In this work,we evaluate the production of hydrogen at intermediate temperatures by proton conducting ceramic cell electrolysis(PCCEL).We demonstrate a highperformance steam electrolysis owing to a composite positrode based on BaGd_(0.8)La_(0.2)Co_(2)O_(6-δ)(BGLC1082)and BaZr0.5Ce0.4Y0.1O3-δ(BZCY541).The high reliability of PCCEL is demonstrated for 1680 h at a current density as high as-0.8 A cm^(-2)close to the thermoneutral cell voltage at 600℃.The electrolysis cell showed a specific energy consumption ranging from 54 to 66 kW h kg^(-1)that is comparable to state-of-the-art low temperature electrolysis technologies,while showing hydrogen production rates systematically higher than commercial solid oxide ceramic cells(SOCs).Compared to SOCs,the results verified the higher performances of PCCs at the relevant operating temperatures,due to the lower activation energy for proton transfer comparing with oxygen ion conduction.However,because of the p-type electronic conduction in protonic ceramics,the energy conversion rate of PCCs is relatively lower in steam electrolysis.The faradaic efficiency of the PCC in electrolysis mode can be increased at lower operating temperatures and in endothermic conditions,making PCCEL a technology of choice to valorize high temperature waste heat from industrial processes into hydrogen.To increase the faradaic efficiency by optimizing the materials,the cell design,or the operating strategy is a key challenge to address for future developments of PCCEL in order to achieve even more superior techno-economic merits.