BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Additive manufacturing(AM)has emerged as one of the most utilized processes in manufacturing due to its ability to produce complex geometries with minimal material waste and greater design freedom.Laser-based AM(LAM)t...Additive manufacturing(AM)has emerged as one of the most utilized processes in manufacturing due to its ability to produce complex geometries with minimal material waste and greater design freedom.Laser-based AM(LAM)technologies use high-power lasers to melt metallic materials,which then solidify to form parts.However,it inherently induces self-equilibrating residual stress during fabrication due to thermal loads and plastic deformation.These residual stresses can cause defects such as delamination,cracking,and distortion,as well as premature failure under service conditions,necessitating mitigation.While post-treatment methods can reduce residual stresses,they are often costly and time-consuming.Therefore,tuning the fabrication process parameters presents a more feasible approach.Accordingly,in addition to providing a comprehensive view of residual stress by their classification,formation mechanisms,measurement methods,and common post-treatment,this paper reviews and compares the studies conducted on the effect of key parameters of the LAM process on the resulting residual stresses.This review focuses on proactively adjusting LAM process parameters as a strategic approach to mitigate residual stress formation.It provides a result of the various parameters influencing residual stress outcomes,such as laser power,scanning speed,beam diameter,hatch spacing,and scanning strategies.Finally,the paper identifies existing research gaps and proposes future studies needed to deepen understanding of the relationship between process parameters and residual stress mitigation in LAM.展开更多
Additive manufacturing(AM),as an advanced manufacturing technology,enables the production of personalized orthopedic implant devices with complex geometries that closely resemble bone structures.Titanium and its alloy...Additive manufacturing(AM),as an advanced manufacturing technology,enables the production of personalized orthopedic implant devices with complex geometries that closely resemble bone structures.Titanium and its alloys are extensively employed in biomedical fields like orthopedics and dentistry,thanks to the excellent compatibility with the human body and high corrosion resistance due to the existence of a thin protective oxide layer known as TiO_(2) upon exposure to oxygen on the surface.However,in joint inflammation,reactive oxygen species like hydrogen peroxide and radicals can damage the passive film on Ti implants,leading to their deterioration.Although AM technology for metallic implants is still developing,advancements in printing and new alloys are crucial for widespread use.This work aims to investigate the corrosion resistance of in-situ alloyed Ti536(Ti5Al3V6Cu)alloy produced through electron beam powder bed fusion(EB-PBF)under simulated peri-implant inflammatory conditions.The corrosion resistance was evaluated using electrochemical experiments conducted in the presence of 0.1%H_(2)O_(2) in a physiological saline solution(0.9%NaCl)to replicate the conditions that may occur during post-operative inflammation.The findings demonstrate that the micro-environment surrounding the implant during peri-implant inflammation is highly corrosive and can lead to the degradation of the TiO_(2) passive layer.Physiological saline with H_(2)O_(2) significantly increased biomaterial open circuit potential up to 0.36 mV vs.Ag/AgCl compared to physiological saline only.Potentiodynamic polarization(PDP)plots confirm this increase,as well.The PDP and electrochemical impedance spectroscopy(EIS)tests indicated that adding Cu does not impact the corrosion resistance of the Ti536 alloy initially under simulated inflammatory conditions,but prolonged immersion leads to enhanced corrosion resistance for all biomaterials tested,indicating the formation of an oxide layer after the reduction of the solution oxidizing power.These results suggest that modifying custom alloys by adding appropriate elements significantly enhances corrosion resistance,particularly in inflammatory conditions.展开更多
Pulse pile-up is a problem in nuclear spectroscopy and nuclear reaction studies that occurs when two pulses overlap and distort each other,degrading the quality of energy and timing information.Different methods have ...Pulse pile-up is a problem in nuclear spectroscopy and nuclear reaction studies that occurs when two pulses overlap and distort each other,degrading the quality of energy and timing information.Different methods have been used for pile-up rejection,both digital and analogue,but some pile-up events may contain pulses of interest and need to be reconstructed.The paper proposes a new method for reconstructing pile-up events acquired with a neutron detector array(NEDA)using an one-dimensional convolutional autoencoder(1D-CAE).The datasets for training and testing the 1D-CAE are created from data acquired from the NEDA.The new pile-up signal reconstruction method is evaluated from the point of view of how similar the reconstructed signals are to the original ones.Furthermore,it is analysed considering the result of the neutron-gamma discrimination based on charge comparison,comparing the result obtained from original and reconstructed signals.展开更多
Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capa...Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.展开更多
Transcatheter intervention allows to deal with multiple cardiovascular diseases1 in patients with impaired clinical conditions and burdened with multiple comorbidities,both with the advantage of planning number and mo...Transcatheter intervention allows to deal with multiple cardiovascular diseases1 in patients with impaired clinical conditions and burdened with multiple comorbidities,both with the advantage of planning number and modalities of the interventions and deciding,where possible,to realize them in a single session.Here we describe the case of a patient affected by severe aortic stenosis and associated cardiac comorbidities(coronary artery disease,atrial fibrillation and left appendage thrombosis)that needed a multimodal clinical and interventional strategy to lead him to the best clinical condition for performing transcatheter aortic valve implantation(TAVI).展开更多
Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to prote...Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.展开更多
This paper presents a thermophysical study approach for a pure environmental control system(ECS),incorporating the geometric dimensions of heat exchangers,ram air duct,and air cycle machine(ACM)blades of the Sabreline...This paper presents a thermophysical study approach for a pure environmental control system(ECS),incorporating the geometric dimensions of heat exchangers,ram air duct,and air cycle machine(ACM)blades of the Sabreliner’s environmental control system.Real flight scenarios are simulated by considering flight input variables such as altitude,aircraft speed,compression ratio of the air cycle machine,and the mass flow rate of bleed air.The study evaluates the coefficient of performance(COP)of the environmental control system,the heat exchanger efficiencies,and the work distribution of the air cycle machine based on five flight scenarios,with a particular focus on considering the effects of humidity on environmental control system performance.The results demonstrate that at cruising altitude(11,000 m),air humidity conditions allow an increase in the COP of around 9.28%compared to dry conditions.Conversely,on land,humidity conditions reduce the performance by 4.26%compared to dry conditions.It was also found that the effects of humidity at high aircraft speeds become negligible.In general terms,the humidity conditions in the air proved to have positive effects on the environmental control system’s performance but negative effects on the heat exchanger efficiencies,reducing them by 0.22%.Additionally,land conditions reflect significant improvements in performance when the compression ratio of the air cycle machine is varied.Furthermore,in the work distribution of the air cycle machine,humidity conditions were demonstrated to consume 2.91%less work fromthe turbine compared to dry conditions.展开更多
Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical...Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical action mechanisms of DCD on bridge structures,a three-span continuous suspension bridge was taken as the engineering background in this study.The influence of different forms of DCD on the internal force and displacement of the components in the side span of the bridge and the structural dynamic characteristics were explored through numerical simulations.The results showed that the lack of DCD caused the main cable and main girder to have large vertical displacements.The stresses of other components were redistributed,and the safety factor of the suspenders at the side span was greatly reduced.The setting of DCD improved the vertical stiffness of the structure.The rigid DCD had larger internal forces,but its control effect on the internal forces at the side span was slightly better than that of the flexible DCD.Both forms of DCD effectively coordinated the deformation of the main cable and main girder and the stress distribution of components in the side span area.The choice of DCD form depends on the topographic factors of bridge sites and the design requirements of related components at the side span.展开更多
Security during remote transmission has been an important concern for researchers in recent years.In this paper,a hierarchical encryption multi-image encryption scheme for people with different security levels is desi...Security during remote transmission has been an important concern for researchers in recent years.In this paper,a hierarchical encryption multi-image encryption scheme for people with different security levels is designed,and a multiimage encryption(MIE)algorithm with row and column confusion and closed-loop bi-directional diffusion is adopted in the paper.While ensuring secure communication of medical image information,people with different security levels have different levels of decryption keys,and differentiated visual effects can be obtained by using the strong sensitivity of chaotic keys.The highest security level can obtain decrypted images without watermarks,and at the same time,patient information and copyright attribution can be verified by obtaining watermark images.The experimental results show that the scheme is sufficiently secure as an MIE scheme with visualized differences and the encryption and decryption efficiency is significantly improved compared to other works.展开更多
The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to...The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to reconstruct the architecture of the oceanic sector from which they derived.The collected data indicate that this oceanic crust consists of a mantle metaperidotites and metaophicalcites,both covered by massive or pillow metabasalts with or without a layer of ophiolite-bearing metabreccias.展开更多
BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To inv...BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To investigate the performance of different ultrasound(US)-based techniques for the non-invasive assessment of liver fibrosis,steatosis,and inflammation in these patients.METHODS We collected data from consecutive patients who underwent liver biopsy for suspected MASLD between January 2019 and December 2021.Two-dimensional shear-wave elastography,sound speed plane-wave US,attenuation plane-wave US,viscosity plane-wave US(Vi.PLUS)using Aixplorer MACH 30 system,and transient elastography and controlled attenuation parameter from FibroScan were measured before biopsy.RESULTS A total of 120 participants were enrolled.Both transient elastography and two-dimensional shear-wave elasto-graphy showed good performance for the diagnosis of advanced fibrosis[area under the receiver operating charac-teristic curve(AUROC)=0.93 and 0.90,respectively].The diagnostic performance of Vi.PLUS for the presence of both ballooning grade≥1 and lobular inflammation≥1 was good with an AUROC of 0.72.A score based on Vi.PLUS,aspartate aminotransferase,and sound speed plane-wave US[viscosity-aspartate aminotransferase-speed of sound MASH ultrasound score(VAS-MASH-US score)]had a good accuracy for the diagnosis of MASH(AUROC=0.75).VAS-MASH-US score>0.6 showed a good sensitivity for MASH diagnosis(79.0%).According to decision curve analysis,the application of the VAS-MASH-US score would lead to a more accurate selection of patients who are candidates to undergo liver biopsy and would reduce the need for invasive procedures for patients at low risk of MASH.CONCLUSION Multiparametric US allows the non-invasive assessment of steatosis,inflammation,and fibrosis in patients with MASLD.Liver viscosity improved the capability of non-invasively identifying patients with MASH.展开更多
Some novel manganese and nickel complexes were synthesized by reacting manganese(Ⅱ) dichloride and nickel(Ⅱ) dichloride with pyridyl-imine ligands differing in the nature of the substituents at the imino nitrogen at...Some novel manganese and nickel complexes were synthesized by reacting manganese(Ⅱ) dichloride and nickel(Ⅱ) dichloride with pyridyl-imine ligands differing in the nature of the substituents at the imino nitrogen atom. All the complexes were characterized by analytical and infrared data: for some of them single crystals were obtained, and their molecular structure was determined by X-ray diffraction. The complexes were used in association with methylaluminoxane(MAO) for the polymerization of 1,3-butadiene obtaining active and selective catalysts giving predominantly 1,2 polybutadiene in case of manganese catalysts and exclusively cis-1,4 polybutadiene in case of nickel catalysts.展开更多
Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient c...Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.展开更多
Assessing the vulnerability of a platform is crucial in its design.In fact,the results obtained from vulnerability analyses provide valuable information,leading to precise design choices or corrective solutions that e...Assessing the vulnerability of a platform is crucial in its design.In fact,the results obtained from vulnerability analyses provide valuable information,leading to precise design choices or corrective solutions that enhance the platform's chances of surviving different scenarios.Such scenarios can involve various types of threats that can affect the platform's survivability.Among such,blast waves impacting the platform's structure represent critical conditions that have not yet been studied in detail.That is,frameworks for vulnerability assessment that can deal with blast loading have not been presented yet.In this context,this work presents a fast-running engineering tool that can quantify the risk that a structure fails when it is subjected to blast loading from the detonation of high explosive-driven threats detonating at various distances from the structure itself.The tool has been implemented in an in-house software that calculates vulnerability to various impacting objects,and its capabilities have been shown through a simplified,yet realistic,case study.The novelty of this research lies in the development of an integrated computational environment capable of calculating the platform's vulnerability to blast waves,without the need for running expensive finite element simulations.In fact,the proposed tool is fully based on analytical models integrated with a probabilistic approach for vulnerability calculation.展开更多
Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have ad...Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have advanced arrival and breeding dates in response to local spring advancement,but conditions experienced during winter seasons may also affect arrival dates and subsequent breeding success.We utilized data collected from 1983 to 2020 in four colonies of Common Swift(Apus apus)in Northern Italy(5486 breeding attempts)to examine the variations of laying date and breeding success in relation to non-breeding conditions(previous winter in Africa)and local conditions in breeding period(spring).Climatic conditions were monitored using the North Atlantic Oscillation(NAO)and El Nino Southern Oscillation(ENSO)indices to describe conditions experienced in winter quarters and the local temperature and rainfall conditions of the breeding area.Common Swifts laid their eggs earlier in warmer springs,and this in turn had a positive effect on breeding success.We did not find evidence for any effects of African winter conditions on laying date nor on breeding success.However,because studies made in the same area have demonstrated a relationship of winter conditions(NAO)on individual survival,our data highlight the importance of considering environmental variables across the annual life cycle to understand variation in Common Swift populations.展开更多
Controllable rock cracking technology is crucial for the exploration and exploitation of deep underground resources.Many existing studies have been dedicated to the laser-assisted rock-weakening technology.It has been...Controllable rock cracking technology is crucial for the exploration and exploitation of deep underground resources.Many existing studies have been dedicated to the laser-assisted rock-weakening technology.It has been proved that laser irradiation can improve drilling and blasting efficiency when combined with mechanical rock fracturing methods,which are irrelevant for borehole stabilization.To improve the latter,this study used laser ablation for borehole reinforcement.The high-power laser was applied to typical rock samples(sandstone,mudstone and coal)in both dry and saturated conditions.Multi-technique observations and measurements were used to fully understand the peculiar modifications of the specimens under laser treatment,i.e.mechanical loading,acoustic emission(AE)monitoring,digital image correlation(DIC)strain field evaluation,infrared thermography(IRT)monitoring and X-ray computed tomography(CT)scanning.The results showed that,in addition to the effects already demonstrated,laser irradiation can improve the strength of the soft rock,especially in the saturated state.The process involved a complicated phase change including melting and evaporation of the matrix under high-temperature and high-pressure to form a glassy high strength silicate material.This process is similar to the reaction between molten lava and water,or the impact of an asteroid on the earth.Inspired by the results,a conceptual path for a new borehole stabilization technology using laser ablation was outlined.展开更多
We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are ...We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are obtained for both the thermal equation and the one-dimensional thermoelastic system,where the impossibility of localization with respect to time is also established.Then,the space estimates are deduced for the multidimensional thermoelastic problem,which allow to show the exponential decay of the energy.展开更多
The NEutron Detector Array(NEDA)is designed to be coupled to gamma-ray spectrometers to enhance the sensitivity of the setup by enabling reaction channel selection through counting of the evaporated neutrons.This arti...The NEutron Detector Array(NEDA)is designed to be coupled to gamma-ray spectrometers to enhance the sensitivity of the setup by enabling reaction channel selection through counting of the evaporated neutrons.This article presents the implementation of a double trigger condition system for NEDA,which improves the acquisition of neutrons and reduces the number of gamma rays acquired.Two independent triggers are generated in the double trigger condition system:one based on charge comparison(CC)and the other on time-of-flight(TOF).These triggers can be combined using OR and AND logic,offering four distinct trigger modes.The developed firmware is added to the previous one in the Virtex 6 field programmable gate array(FPGA)present in the system,which also includes signal processing,baseline correction,and various trigger logic blocks.The performance of the trigger system is evaluated using data from the E703 experiment performed at GANIL.The four trigger modes are applied to the same data,and a subsequent offline analysis is performed.It is shown that most of the detected neutrons are preserved with the AND mode,and the total number of gamma rays is significantly reduced.Compared with the CC trigger mode,the OR trigger mode allows increasing the selection of neutrons.In addition,it is demonstrated that if the OR mode is selected,the online CC trigger threshold can be raised without losing neutrons.展开更多
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
文摘Additive manufacturing(AM)has emerged as one of the most utilized processes in manufacturing due to its ability to produce complex geometries with minimal material waste and greater design freedom.Laser-based AM(LAM)technologies use high-power lasers to melt metallic materials,which then solidify to form parts.However,it inherently induces self-equilibrating residual stress during fabrication due to thermal loads and plastic deformation.These residual stresses can cause defects such as delamination,cracking,and distortion,as well as premature failure under service conditions,necessitating mitigation.While post-treatment methods can reduce residual stresses,they are often costly and time-consuming.Therefore,tuning the fabrication process parameters presents a more feasible approach.Accordingly,in addition to providing a comprehensive view of residual stress by their classification,formation mechanisms,measurement methods,and common post-treatment,this paper reviews and compares the studies conducted on the effect of key parameters of the LAM process on the resulting residual stresses.This review focuses on proactively adjusting LAM process parameters as a strategic approach to mitigate residual stress formation.It provides a result of the various parameters influencing residual stress outcomes,such as laser power,scanning speed,beam diameter,hatch spacing,and scanning strategies.Finally,the paper identifies existing research gaps and proposes future studies needed to deepen understanding of the relationship between process parameters and residual stress mitigation in LAM.
基金Open access funding provided by Politecnico di Torino within the CRUI-CARE Agreement.
文摘Additive manufacturing(AM),as an advanced manufacturing technology,enables the production of personalized orthopedic implant devices with complex geometries that closely resemble bone structures.Titanium and its alloys are extensively employed in biomedical fields like orthopedics and dentistry,thanks to the excellent compatibility with the human body and high corrosion resistance due to the existence of a thin protective oxide layer known as TiO_(2) upon exposure to oxygen on the surface.However,in joint inflammation,reactive oxygen species like hydrogen peroxide and radicals can damage the passive film on Ti implants,leading to their deterioration.Although AM technology for metallic implants is still developing,advancements in printing and new alloys are crucial for widespread use.This work aims to investigate the corrosion resistance of in-situ alloyed Ti536(Ti5Al3V6Cu)alloy produced through electron beam powder bed fusion(EB-PBF)under simulated peri-implant inflammatory conditions.The corrosion resistance was evaluated using electrochemical experiments conducted in the presence of 0.1%H_(2)O_(2) in a physiological saline solution(0.9%NaCl)to replicate the conditions that may occur during post-operative inflammation.The findings demonstrate that the micro-environment surrounding the implant during peri-implant inflammation is highly corrosive and can lead to the degradation of the TiO_(2) passive layer.Physiological saline with H_(2)O_(2) significantly increased biomaterial open circuit potential up to 0.36 mV vs.Ag/AgCl compared to physiological saline only.Potentiodynamic polarization(PDP)plots confirm this increase,as well.The PDP and electrochemical impedance spectroscopy(EIS)tests indicated that adding Cu does not impact the corrosion resistance of the Ti536 alloy initially under simulated inflammatory conditions,but prolonged immersion leads to enhanced corrosion resistance for all biomaterials tested,indicating the formation of an oxide layer after the reduction of the solution oxidizing power.These results suggest that modifying custom alloys by adding appropriate elements significantly enhances corrosion resistance,particularly in inflammatory conditions.
基金partially supported by MICIU MCIN/AEI/10.13039/501100011033Spain with grant PID2020-118265GB-C42,-C44,PRTR-C17.I01+1 种基金Generalitat Valenciana,Spain with grant CIPROM/2022/54,ASFAE/2022/031,CIAPOS/2021/114the EU NextGenerationEU,ESF funds,and the National Science Centre (NCN),Poland (grant No.2020/39/D/ST2/00466)
文摘Pulse pile-up is a problem in nuclear spectroscopy and nuclear reaction studies that occurs when two pulses overlap and distort each other,degrading the quality of energy and timing information.Different methods have been used for pile-up rejection,both digital and analogue,but some pile-up events may contain pulses of interest and need to be reconstructed.The paper proposes a new method for reconstructing pile-up events acquired with a neutron detector array(NEDA)using an one-dimensional convolutional autoencoder(1D-CAE).The datasets for training and testing the 1D-CAE are created from data acquired from the NEDA.The new pile-up signal reconstruction method is evaluated from the point of view of how similar the reconstructed signals are to the original ones.Furthermore,it is analysed considering the result of the neutron-gamma discrimination based on charge comparison,comparing the result obtained from original and reconstructed signals.
基金supported in part by funding from BeiGene,Ltd.,USA(Grant No.:KPR081)with additional support from the Alessandra Bono Foundation,Italy.
文摘Pamiparib is a potent and selective oral poly(adenosine diphosphate(ADP)-ribose)-polymerase(PARP)1/2inhibitor(PARPi).Pamiparib has good bioavailability and shows greater cytotoxic potency and similar DNA-trapping capacity compared to olaparib.It is not affected by adenosine triphosphate(ATP)-binding cassette transporters.
文摘Transcatheter intervention allows to deal with multiple cardiovascular diseases1 in patients with impaired clinical conditions and burdened with multiple comorbidities,both with the advantage of planning number and modalities of the interventions and deciding,where possible,to realize them in a single session.Here we describe the case of a patient affected by severe aortic stenosis and associated cardiac comorbidities(coronary artery disease,atrial fibrillation and left appendage thrombosis)that needed a multimodal clinical and interventional strategy to lead him to the best clinical condition for performing transcatheter aortic valve implantation(TAVI).
基金supported by:Fondazione Telethon-Italy(No.GGP19128 to AP)Fondazione Cariplo-Italy(No.2021-1544 to RC)+14 种基金Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica(AriSLA)-Italy(No.MLOpathy to APTarget-RAN to AP)Association Française contre les Myopathies-France(AFM Telethon No.23236 to AP)Kennedy’s Disease Association-USA(2018 grant to RC2020 grant to MG)Ministero dell’Universitàe della Ricerca(MIUR)-Italy(PRIN-Progetti di ricerca di interesse nazionale(No.2017F2A2C5 to APNo.2022EFLFL8 to APNo.2020PBS5MJ to VCNo.2022KSJZF5 to VC)PRIN-Progetti di ricerca di interesse nazionale-bando 2022,PNRR finanziato dall’Unione europea-Next Generation EU,componente M4C2,investimento 1.1(No.P2022B5J32 to RC and No.P20225R4Y5 to VC)CN3:RNA-Codice Proposta:CN_00000041Tematica Sviluppo di terapia genica e farmaci con tecnologia a RNA(Centro Nazionale di Ricerca-CN3 National Center for Gene Therapy and Drugs based on RNA Technology to AP)Progetto Dipartimenti di Eccellenza(to DiSFeB)Ministero della Salute,Agenzia Italiana del Farmaco(AIFA)-Italy(Co_ALS to AP)Universitàdegli Studi di Milano(piano di sviluppo della ricerca(PSR)UNIMI-linea B(to RC and BT).
文摘Heat shock protein family B(small)member 8(HSPB8)is a 22 kDa ubiquitously expressed protein belonging to the family of small heat shock proteins.HSPB8 is involved in various cellular mechanisms mainly related to proteotoxic stress response and in other processes such as inflammation,cell division,and migration.HSPB8 binds misfolded clients to prevent their aggregation by assisting protein refolding or degradation through chaperone-assisted selective autophagy.In line with this function,the pro-degradative activity of HSPB8 has been found protective in several neurodegenerative and neuromuscular diseases characterized by protein misfolding and aggregation.In cancer,HSPB8 has a dual role being capable of exerting either a pro-or an anti-tumoral activity depending on the pathways and factors expressed by the model of cancer under investigation.Moreover,HSPB8 exerts a protective function in different diseases by modulating the inflammatory response,which characterizes not only neurodegenerative diseases,but also other chronic or acute conditions affecting the nervous system,such as multiple sclerosis and intracerebellar hemorrhage.Of note,HSPB8 modulation may represent a therapeutic approach in other neurological conditions that develop as a secondary consequence of other diseases.This is the case of cognitive impairment related to diabetes mellitus,in which HSPB8 exerts a protective activity by assuring mitochondrial homeostasis.This review aims to summarize the diverse and multiple functions of HSPB8 in different pathological conditions,focusing on the beneficial effects of its modulation.Drug-based and alternative therapeutic approaches targeting HSPB8 and its regulated pathways will be discussed,emphasizing how new strategies for cell and tissue-specific delivery represent an avenue to advance in disease treatments.
文摘This paper presents a thermophysical study approach for a pure environmental control system(ECS),incorporating the geometric dimensions of heat exchangers,ram air duct,and air cycle machine(ACM)blades of the Sabreliner’s environmental control system.Real flight scenarios are simulated by considering flight input variables such as altitude,aircraft speed,compression ratio of the air cycle machine,and the mass flow rate of bleed air.The study evaluates the coefficient of performance(COP)of the environmental control system,the heat exchanger efficiencies,and the work distribution of the air cycle machine based on five flight scenarios,with a particular focus on considering the effects of humidity on environmental control system performance.The results demonstrate that at cruising altitude(11,000 m),air humidity conditions allow an increase in the COP of around 9.28%compared to dry conditions.Conversely,on land,humidity conditions reduce the performance by 4.26%compared to dry conditions.It was also found that the effects of humidity at high aircraft speeds become negligible.In general terms,the humidity conditions in the air proved to have positive effects on the environmental control system’s performance but negative effects on the heat exchanger efficiencies,reducing them by 0.22%.Additionally,land conditions reflect significant improvements in performance when the compression ratio of the air cycle machine is varied.Furthermore,in the work distribution of the air cycle machine,humidity conditions were demonstrated to consume 2.91%less work fromthe turbine compared to dry conditions.
基金The National Natural Science Foundation of China(No.52338011)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_0067).
文摘Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical action mechanisms of DCD on bridge structures,a three-span continuous suspension bridge was taken as the engineering background in this study.The influence of different forms of DCD on the internal force and displacement of the components in the side span of the bridge and the structural dynamic characteristics were explored through numerical simulations.The results showed that the lack of DCD caused the main cable and main girder to have large vertical displacements.The stresses of other components were redistributed,and the safety factor of the suspenders at the side span was greatly reduced.The setting of DCD improved the vertical stiffness of the structure.The rigid DCD had larger internal forces,but its control effect on the internal forces at the side span was slightly better than that of the flexible DCD.Both forms of DCD effectively coordinated the deformation of the main cable and main girder and the stress distribution of components in the side span area.The choice of DCD form depends on the topographic factors of bridge sites and the design requirements of related components at the side span.
基金Project supported by the National Natural Science Foundation of China(Grant No.62061014)the Natural Science Foundation of Liaoning province of China(Grant No.2020-MS-274).
文摘Security during remote transmission has been an important concern for researchers in recent years.In this paper,a hierarchical encryption multi-image encryption scheme for people with different security levels is designed,and a multiimage encryption(MIE)algorithm with row and column confusion and closed-loop bi-directional diffusion is adopted in the paper.While ensuring secure communication of medical image information,people with different security levels have different levels of decryption keys,and differentiated visual effects can be obtained by using the strong sensitivity of chaotic keys.The highest security level can obtain decrypted images without watermarks,and at the same time,patient information and copyright attribution can be verified by obtaining watermark images.The experimental results show that the scheme is sufficiently secure as an MIE scheme with visualized differences and the encryption and decryption efficiency is significantly improved compared to other works.
基金supported by PRIN 2020 project(Resp.Michele Marroni)Claudia D’Oriano(INGV)Matteo Masotta and Danis Filimon(Earth Science Dept)are also thanked for analytical support in the laboratoriesThis work benefited from the PRA 2022 project handled by Francesca Meneghini.
文摘The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to reconstruct the architecture of the oceanic sector from which they derived.The collected data indicate that this oceanic crust consists of a mantle metaperidotites and metaophicalcites,both covered by massive or pillow metabasalts with or without a layer of ophiolite-bearing metabreccias.
文摘BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To investigate the performance of different ultrasound(US)-based techniques for the non-invasive assessment of liver fibrosis,steatosis,and inflammation in these patients.METHODS We collected data from consecutive patients who underwent liver biopsy for suspected MASLD between January 2019 and December 2021.Two-dimensional shear-wave elastography,sound speed plane-wave US,attenuation plane-wave US,viscosity plane-wave US(Vi.PLUS)using Aixplorer MACH 30 system,and transient elastography and controlled attenuation parameter from FibroScan were measured before biopsy.RESULTS A total of 120 participants were enrolled.Both transient elastography and two-dimensional shear-wave elasto-graphy showed good performance for the diagnosis of advanced fibrosis[area under the receiver operating charac-teristic curve(AUROC)=0.93 and 0.90,respectively].The diagnostic performance of Vi.PLUS for the presence of both ballooning grade≥1 and lobular inflammation≥1 was good with an AUROC of 0.72.A score based on Vi.PLUS,aspartate aminotransferase,and sound speed plane-wave US[viscosity-aspartate aminotransferase-speed of sound MASH ultrasound score(VAS-MASH-US score)]had a good accuracy for the diagnosis of MASH(AUROC=0.75).VAS-MASH-US score>0.6 showed a good sensitivity for MASH diagnosis(79.0%).According to decision curve analysis,the application of the VAS-MASH-US score would lead to a more accurate selection of patients who are candidates to undergo liver biopsy and would reduce the need for invasive procedures for patients at low risk of MASH.CONCLUSION Multiparametric US allows the non-invasive assessment of steatosis,inflammation,and fibrosis in patients with MASLD.Liver viscosity improved the capability of non-invasively identifying patients with MASH.
文摘Some novel manganese and nickel complexes were synthesized by reacting manganese(Ⅱ) dichloride and nickel(Ⅱ) dichloride with pyridyl-imine ligands differing in the nature of the substituents at the imino nitrogen atom. All the complexes were characterized by analytical and infrared data: for some of them single crystals were obtained, and their molecular structure was determined by X-ray diffraction. The complexes were used in association with methylaluminoxane(MAO) for the polymerization of 1,3-butadiene obtaining active and selective catalysts giving predominantly 1,2 polybutadiene in case of manganese catalysts and exclusively cis-1,4 polybutadiene in case of nickel catalysts.
文摘Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.
文摘Assessing the vulnerability of a platform is crucial in its design.In fact,the results obtained from vulnerability analyses provide valuable information,leading to precise design choices or corrective solutions that enhance the platform's chances of surviving different scenarios.Such scenarios can involve various types of threats that can affect the platform's survivability.Among such,blast waves impacting the platform's structure represent critical conditions that have not yet been studied in detail.That is,frameworks for vulnerability assessment that can deal with blast loading have not been presented yet.In this context,this work presents a fast-running engineering tool that can quantify the risk that a structure fails when it is subjected to blast loading from the detonation of high explosive-driven threats detonating at various distances from the structure itself.The tool has been implemented in an in-house software that calculates vulnerability to various impacting objects,and its capabilities have been shown through a simplified,yet realistic,case study.The novelty of this research lies in the development of an integrated computational environment capable of calculating the platform's vulnerability to blast waves,without the need for running expensive finite element simulations.In fact,the proposed tool is fully based on analytical models integrated with a probabilistic approach for vulnerability calculation.
文摘Climate change can affect rainfall and temperature worldwide,and the ability of birds to react to these changes can be mirrored by studying population phenology and their breeding success.Some European species have advanced arrival and breeding dates in response to local spring advancement,but conditions experienced during winter seasons may also affect arrival dates and subsequent breeding success.We utilized data collected from 1983 to 2020 in four colonies of Common Swift(Apus apus)in Northern Italy(5486 breeding attempts)to examine the variations of laying date and breeding success in relation to non-breeding conditions(previous winter in Africa)and local conditions in breeding period(spring).Climatic conditions were monitored using the North Atlantic Oscillation(NAO)and El Nino Southern Oscillation(ENSO)indices to describe conditions experienced in winter quarters and the local temperature and rainfall conditions of the breeding area.Common Swifts laid their eggs earlier in warmer springs,and this in turn had a positive effect on breeding success.We did not find evidence for any effects of African winter conditions on laying date nor on breeding success.However,because studies made in the same area have demonstrated a relationship of winter conditions(NAO)on individual survival,our data highlight the importance of considering environmental variables across the annual life cycle to understand variation in Common Swift populations.
基金supported by the National Natural Science Foundation of China(Grant No.51804296)China Scholarship Council Grant(Grant No.CSC#202006425019).
文摘Controllable rock cracking technology is crucial for the exploration and exploitation of deep underground resources.Many existing studies have been dedicated to the laser-assisted rock-weakening technology.It has been proved that laser irradiation can improve drilling and blasting efficiency when combined with mechanical rock fracturing methods,which are irrelevant for borehole stabilization.To improve the latter,this study used laser ablation for borehole reinforcement.The high-power laser was applied to typical rock samples(sandstone,mudstone and coal)in both dry and saturated conditions.Multi-technique observations and measurements were used to fully understand the peculiar modifications of the specimens under laser treatment,i.e.mechanical loading,acoustic emission(AE)monitoring,digital image correlation(DIC)strain field evaluation,infrared thermography(IRT)monitoring and X-ray computed tomography(CT)scanning.The results showed that,in addition to the effects already demonstrated,laser irradiation can improve the strength of the soft rock,especially in the saturated state.The process involved a complicated phase change including melting and evaporation of the matrix under high-temperature and high-pressure to form a glassy high strength silicate material.This process is similar to the reaction between molten lava and water,or the impact of an asteroid on the earth.Inspired by the results,a conceptual path for a new borehole stabilization technology using laser ablation was outlined.
基金part of the project“Qualitative and numerical analyses of some thermomechanics problems(ACUANUTER)”(Ref.PID2024-156827NB-I00)。
文摘We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are obtained for both the thermal equation and the one-dimensional thermoelastic system,where the impossibility of localization with respect to time is also established.Then,the space estimates are deduced for the multidimensional thermoelastic problem,which allow to show the exponential decay of the energy.
基金supported by MICIU MCIN/AEI/10.13039/501100011033Spain with Grant PID2020-118265GB-C42,-C44,PRTR-C17.I01Generalitat Valenciana,Spain with Grant CIPROM/2022/54,ASFAE/2022/031,CIAPOS/2021/114 and by the EU NextGenerationEU,ESF funds.This work was also supported by the National Science Centre(NCN),Poland(Grant No.2020/39/D/ST2/00466).
文摘The NEutron Detector Array(NEDA)is designed to be coupled to gamma-ray spectrometers to enhance the sensitivity of the setup by enabling reaction channel selection through counting of the evaporated neutrons.This article presents the implementation of a double trigger condition system for NEDA,which improves the acquisition of neutrons and reduces the number of gamma rays acquired.Two independent triggers are generated in the double trigger condition system:one based on charge comparison(CC)and the other on time-of-flight(TOF).These triggers can be combined using OR and AND logic,offering four distinct trigger modes.The developed firmware is added to the previous one in the Virtex 6 field programmable gate array(FPGA)present in the system,which also includes signal processing,baseline correction,and various trigger logic blocks.The performance of the trigger system is evaluated using data from the E703 experiment performed at GANIL.The four trigger modes are applied to the same data,and a subsequent offline analysis is performed.It is shown that most of the detected neutrons are preserved with the AND mode,and the total number of gamma rays is significantly reduced.Compared with the CC trigger mode,the OR trigger mode allows increasing the selection of neutrons.In addition,it is demonstrated that if the OR mode is selected,the online CC trigger threshold can be raised without losing neutrons.
