Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning ofte...BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.展开更多
The particularity and practicality of harmony operations of close-coupling multiple helicopters indicate that the researches on it are urgent and necessary, Using the model that describes two hovering helicopters carr...The particularity and practicality of harmony operations of close-coupling multiple helicopters indicate that the researches on it are urgent and necessary, Using the model that describes two hovering helicopters carrying one heavy load, an inertia coordinate system and body coordinate systems of each sub-system are established. A nonlinear force model is established too. The equilibrium computation results can be regarded as the reference control inputs of the flight control system under hovering or low-speed flight condition. After the establishment of a translation kinematics model and a posture kinematics model, a coupling dynamics model of the multiple helicopter system is set up. The results can also be regarded as the base to analyze stabilization and design a controller for a close-coupling multiple helicopters harmony operation system.展开更多
In the Kaiping Coal field,mining of five coal seams,located within 80 m in the Kailuan Group,#5,#7,#8,#9 and#12 coal seam,is difficult due to small interburden thickness,concentrated stress distributions,high coal sea...In the Kaiping Coal field,mining of five coal seams,located within 80 m in the Kailuan Group,#5,#7,#8,#9 and#12 coal seam,is difficult due to small interburden thickness,concentrated stress distributions,high coal seam metamorphism,and complex geological conditions.By using the ZTR12 geological penetration radar(GPR)survey combined with borehole observations,the overburden caving due to mining of the five coals seams was measured.The development characteristics of full-cover rock fractures after mining were obtained from the GPR scan,which provides a measurement basis for the control of rock strata in close multiple coal seam mining.For the first time,it was found that the overburden caving pattern shows a periodic triangular caved characteristic.Furthermore,it is proposed that an upright triangular collapsed pile masonry and an inverted triangular with larger fragments piled up alternately appear in the lower gob.The research results show that the roof structure formed in the gob area can support the key overlying strata,which is beneficial to ensure the integrity and stability of the upper coal seams in multiple-seam mining of close coal seams.展开更多
Room-and-pillar mining with pillar recovery has historically been associated with more than 25% of all ground fall fatalities in underground coal mines in the United States.The risk of ground falls during pillar recov...Room-and-pillar mining with pillar recovery has historically been associated with more than 25% of all ground fall fatalities in underground coal mines in the United States.The risk of ground falls during pillar recovery increases in multiple-seam mining conditions.The hazards associated with pillar recovery in multiple-seam mining include roof cutters, roof falls, rib rolls, coal outbursts, and floor heave.When pillar recovery is planned in multiple seams, it is critical to properly design the mining sequence and panel layout to minimize potential seam interaction.This paper addresses geotechnical considerations for concurrent pillar recovery in two coal seams with 21 m of interburden under about 305 m of depth of cover.The study finds that, for interburden thickness of 21 m, the multiple-seam mining influence zone in the lower seam is directly under the barrier pillar within about 30 m from the gob edge of the upper seam.The peak stress in the interburden transfers down at an angle of approximately 20°away from the gob, and the entries and crosscuts in the influence zone are subjected to elevated stress during development and retreat.The study also suggests that, for full pillar recovery in close-distance multiple-seam scenarios,it is optimal to superimpose the gobs in both seams, but it is not necessary to superimpose the pillars.If the entries and/or crosscuts in the lower seam are developed outside the gob line of the upper seam,additional roof and rib support needs to be considered to account for the elevated stress in the multiple-seam influence zone.展开更多
A roadway within ultra-close multiple-seams(RUCMSs) is one of the most difficult supported coal roadways to deal with in underground coal mines. This is usually due to the unknown stress distributions, improper roadwa...A roadway within ultra-close multiple-seams(RUCMSs) is one of the most difficult supported coal roadways to deal with in underground coal mines. This is usually due to the unknown stress distributions, improper roadway layout, and unreasonable support parameters. In order to solve this support problem and effectively save RUCMSs from frequent and abrupt disasters(such as serious deformation of the surrounding rock, roof cave ins, and coal side collapse), a comprehensive method is adopted here which includes theoretical analysis, numerical simulation, and field monitoring. A mechanical model was constructed to determine the stress distribution in the coal pillar after two sides of a longwall panel had been mined. Based on this model, the horizontal, vertical, and tangential stress equations for the plane below the floor of the upper-left coal pillar were deduced. In addition, a typical coal mine(the Jinggonger colliery, located in Shuozhou city, Shanxi province, China) with an average distance between its 9# and 11# coal seams of less than 8.0 was chosen to conduct research on the proper layout and reasonable support required for a typical coal roadway located within coal seam 11#. Using FLAC3D(Fast Lagrangian Analysis of Continua in 3-Dimensions) numerical software, eight schemes were designed with different horizontal distances(d) between the center lines of the coal pillar and the roadway in the lower coal seam(RLCS). The simulations and detailed analysis indicate that the proper distances required are between 22.5 and 27.5 m. A total of 20 simulation schemes were used to investigate the factors influencing the support provided by the key bolts(bolt length, spacing, distance between two rows, installation angle, and pre-tightening force). The results were analyzed and used to determine reasonable values for the support parameters. Field results show that the stability and strength of the RLCS can be effectively safeguarded using a combination of researched stress distribution characteristics, proper layout of the RLCS, and correct support parameters.展开更多
In order to solve the problem of reliability modeling and the analysis of complex systems with multiple closed-loop feedbacks,a new reliability analysis method for repairable systems with multiple closed-loop feedback...In order to solve the problem of reliability modeling and the analysis of complex systems with multiple closed-loop feedbacks,a new reliability analysis method for repairable systems with multiple closed-loop feedbacks is proposed based on the goal-oriented(GO)methodology.Firstly,the basic theories and advantages of GO method are introduced.Secondly,a type-24B multiple closed-loop feedback structure operator is proposed through GO method with its operation formula given,which expands the types of GO method operators and the application scope of their reliability analysis.Finally,taking a certain type of diesel engine fuel supply system an example,the quantitative and qualitative analysis is carried out through GO method,Monte Carlo simulation as well as FTA respectively.The availability results verify the availability of the proposed type-24B operator in the reliability analysis of multiple closed-loop feedback systems.The qualitative analysis results indicate the accuracy and usability of the GO method as a qualitative analysis method.展开更多
Effect of multiple respiratory gas monitoring (MRGM ) on inspiredconcentration of oxygen in circult system during closed anesthesia was studied in 5l adult patients scheduled for abdominal surgery. Required flow rate ...Effect of multiple respiratory gas monitoring (MRGM ) on inspiredconcentration of oxygen in circult system during closed anesthesia was studied in 5l adult patients scheduled for abdominal surgery. Required flow rate of fresh oxygen (OFR), inspired oxygen concentration (FiO2 ) and oxygen saturation of pulse oximeter (SpO2) were measured continu0usly. Patients were equally divided into three groups at randorn, group C (no MRGN used ), group M, (using MRGM with its tail gas returned to circuit system), group M2 (using MRGM without tail gas returned ). The results revealed that during 180 min of closed anesthesia, OFR required in group C and M, were about 200-230 ml/min, and in group M, it was ab0ut 400 ml/min. In group C FiO2 decreased by about 10 % after 60 min of closed anesthesia (P<0. 01, 60 min vs 0 min ) and then stayed stable at this level. In group M,, FiO2 decreased by 16% at 60 min and 34 % at 180 min and the decrease was significantly greater than that in gr0up C (P<0. 01). In group Me, FiO2 remained c0nstant during closed anesthesia, which was much high(Jr than those in group C and M,. The tail gas of Capnomac Ultima MRGM contained less oxygen than its sample gas drawn fr0m circuit system simuItaneously.展开更多
Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells ...Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
A closed-loop control allocation method is proposed for a class of aircraft with multiple actuators. Nonlinear dynamic inversion is used to design the baseline attitude controller and derive the desired moment increme...A closed-loop control allocation method is proposed for a class of aircraft with multiple actuators. Nonlinear dynamic inversion is used to design the baseline attitude controller and derive the desired moment increment. And a feedback loop for the moment increment produced by the deflections of actuators is added to the angular rate loop, then the error between the desired and actual moment increment is the input of the dynamic control allocation. Subsequently, the stability of the closed-loop dynamic control allocation system is analyzed in detail. Especially, the closedloop system stability is also analyzed in the presence of two types of actuator failures： loss of effectiveness and lock-in-place actuator failures, where a fault detection subsystem to identify the actuator failures is absent. Finally, the proposed method is applied to a canard rotor/wing （CRW） aircraft model in fixed-wing mode, which has multiple actuators for flight control. The nonlinear simulation demonstrates that this method can guarantee the stability and tracking performance whether the actuators are healthy or fail.展开更多
Rationally regulating the porosity of hard carbon(HC),especially the closed pores matching the low potential plateau and the ultra-microporous structure suitable for Na+embedding,has been shown to be the key to improv...Rationally regulating the porosity of hard carbon(HC),especially the closed pores matching the low potential plateau and the ultra-microporous structure suitable for Na+embedding,has been shown to be the key to improving the sodium storage performance and initial coulombic efficiency(ICE).However,the preparation of such HC materials with specific pore structures still faces great challenges.Herein,a simple pre-oxidation strategy is employed to construct abundant closed ultra-microporous structures in soy protein powder-derived HC material,achieving a significant improvement in its ICE and platform capacity.The pre-oxidation process promotes the cross-linking degree of the soy protein,thereby hindering the directional growth of graphite domains during the carbonization process.The optimized HC exhibits ultra-high platform capacity(329 mAh g^(-1))and considerable energy density(148.5 Wh kg^(-1)).Based on the ex-situ Raman and X-ray photoelectron spectroscopy characterization results,the excellent sodium storage capacity of the HC material is attributed to the synergistic effect of adsorption-intercalation/filling.The presented work provides novel insights into the synthesis of other biomass-derived HC materials with abundant closed ultra-micro pores.展开更多
We present the essential stellar parameters of the close visual triple system HD 2893 using Al-Wardat's method for analyzing binary and multiple star systems in conjunction with Kurucz's model atmospheres.This...We present the essential stellar parameters of the close visual triple system HD 2893 using Al-Wardat's method for analyzing binary and multiple star systems in conjunction with Kurucz's model atmospheres.This method accurately computes the spectrophotometric stellar masses through a combined synthetic spectral energy distribution approach that compares the results with observed data.The vigorous approach uses spectroscopic,photometric,and dynamical analysis to yield precise results.The method implements Gaia DR3 measurements and other measurements like those of Hipparcos and 2MASS All-Sky Catalog as a guide for the best fit between the synthetic spectra and observed photometry.The analysis gives precise spectrophotometric stellar masses for the system being M_(Sph)^(A)=1.20±0.07M⊙,M_(Sph)^(B)=1.09±0.06M⊙,and M_(Sph)^(C)=0.46±0.01M⊙.It shows that the three components are main sequence stars with an estimated age of around 1.0 Gyr.When integrated with the dynamical analysis,a new dynamical parallax for the system is obtained,π_(dyn)=13.8528±0.20 mas.Additionally,the discussion covers the formation and evolution of the triple system.展开更多
Closed-loop deep brain stimulation（DBS）：DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure ...Closed-loop deep brain stimulation（DBS）：DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure have been previously made.Several factors affect the DBS clinical outcomes such as lead position,programming technique,展开更多
The extended trading close(ETC)provides institutional investors an opportunity to trade at the closing price after the regular trading session(RTS)and disclosing the order imbalances to other market participants.ETCs ...The extended trading close(ETC)provides institutional investors an opportunity to trade at the closing price after the regular trading session(RTS)and disclosing the order imbalances to other market participants.ETCs exist in the Nasdaq,the SSE STAR,the SZSE ChiNext and the TWSE.To help a risk-averse institutional investor take advantage of the RTS and the ETC for liquidation,we develop a multistage dynamic programming model including the ETC,and derive recursive solutions for the multiple trading days scenario with closed-form solutions for the scenario with only two trading days.We also verify that the ETC is able to mitigate extreme price movements caused by fast liquidation,which is also a goal of the ETC set out by the SSE STAR and the SZSE ChiNext.Finally,we derive three results.First,an institutional investor can reduce execution costs after the introduction of the ETC.Second,a critical trading day exists,and to avoid prematurely revealing trading intentions,the investor should not trade in the ETC until such day.Third,even though the ETC orders submitted by the investor are unfilled,implementation of the ETC encourages the investor to change the liquidation strategy in the RTS,which reduces extreme price movements.In summary,the practical implications of this paper are that the investor should not trade during the ETC on the front few days to avoid prematurely revealing the investor’s trading intention by unfilled orders in the ETC and that introducing the ETC can reduce liquidation costs and extreme price movements.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to d...This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Supported by Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science and Technology Bureau),No.2023MSXM060.
文摘BACKGROUND The accurate prediction of lymph node metastasis(LNM)is crucial for managing locally advanced(T3/T4)colorectal cancer(CRC).However,both traditional histopathology and standard slide-level deep learning often fail to capture the sparse and diagnostically critical features of metastatic potential.AIM To develop and validate a case-level multiple-instance learning(MIL)framework mimicking a pathologist's comprehensive review and improve T3/T4 CRC LNM prediction.METHODS The whole-slide images of 130 patients with T3/T4 CRC were retrospectively collected.A case-level MIL framework utilising the CONCH v1.5 and UNI2-h deep learning models was trained on features from all haematoxylin and eosinstained primary tumour slides for each patient.These pathological features were subsequently integrated with clinical data,and model performance was evaluated using the area under the curve(AUC).RESULTS The case-level framework demonstrated superior LNM prediction over slide-level training,with the CONCH v1.5 model achieving a mean AUC(±SD)of 0.899±0.033 vs 0.814±0.083,respectively.Integrating pathology features with clinical data further enhanced performance,yielding a top model with a mean AUC of 0.904±0.047,in sharp contrast to a clinical-only model(mean AUC 0.584±0.084).Crucially,a pathologist’s review confirmed that the model-identified high-attention regions correspond to known high-risk histopathological features.CONCLUSION A case-level MIL framework provides a superior approach for predicting LNM in advanced CRC.This method shows promise for risk stratification and therapy decisions,requiring further validation.
基金National Natural Science Foundation of China(60475039)
文摘The particularity and practicality of harmony operations of close-coupling multiple helicopters indicate that the researches on it are urgent and necessary, Using the model that describes two hovering helicopters carrying one heavy load, an inertia coordinate system and body coordinate systems of each sub-system are established. A nonlinear force model is established too. The equilibrium computation results can be regarded as the reference control inputs of the flight control system under hovering or low-speed flight condition. After the establishment of a translation kinematics model and a posture kinematics model, a coupling dynamics model of the multiple helicopter system is set up. The results can also be regarded as the base to analyze stabilization and design a controller for a close-coupling multiple helicopters harmony operation system.
基金The research is supported by National Key R&D Program of China(No.2017YFC060300204)National Natural Science Foundation of China(No.52074293)+2 种基金Hebei Province Natural Science Foundation of China(No.E2020402041)Yue Qi Young Scholar Project,CUMTB and Yue Qi Distinguished Scholar Project(No.800015Z1138)China University of Mining&Technology,Beijing.
文摘In the Kaiping Coal field,mining of five coal seams,located within 80 m in the Kailuan Group,#5,#7,#8,#9 and#12 coal seam,is difficult due to small interburden thickness,concentrated stress distributions,high coal seam metamorphism,and complex geological conditions.By using the ZTR12 geological penetration radar(GPR)survey combined with borehole observations,the overburden caving due to mining of the five coals seams was measured.The development characteristics of full-cover rock fractures after mining were obtained from the GPR scan,which provides a measurement basis for the control of rock strata in close multiple coal seam mining.For the first time,it was found that the overburden caving pattern shows a periodic triangular caved characteristic.Furthermore,it is proposed that an upright triangular collapsed pile masonry and an inverted triangular with larger fragments piled up alternately appear in the lower gob.The research results show that the roof structure formed in the gob area can support the key overlying strata,which is beneficial to ensure the integrity and stability of the upper coal seams in multiple-seam mining of close coal seams.
文摘Room-and-pillar mining with pillar recovery has historically been associated with more than 25% of all ground fall fatalities in underground coal mines in the United States.The risk of ground falls during pillar recovery increases in multiple-seam mining conditions.The hazards associated with pillar recovery in multiple-seam mining include roof cutters, roof falls, rib rolls, coal outbursts, and floor heave.When pillar recovery is planned in multiple seams, it is critical to properly design the mining sequence and panel layout to minimize potential seam interaction.This paper addresses geotechnical considerations for concurrent pillar recovery in two coal seams with 21 m of interburden under about 305 m of depth of cover.The study finds that, for interburden thickness of 21 m, the multiple-seam mining influence zone in the lower seam is directly under the barrier pillar within about 30 m from the gob edge of the upper seam.The peak stress in the interburden transfers down at an angle of approximately 20°away from the gob, and the entries and crosscuts in the influence zone are subjected to elevated stress during development and retreat.The study also suggests that, for full pillar recovery in close-distance multiple-seam scenarios,it is optimal to superimpose the gobs in both seams, but it is not necessary to superimpose the pillars.If the entries and/or crosscuts in the lower seam are developed outside the gob line of the upper seam,additional roof and rib support needs to be considered to account for the elevated stress in the multiple-seam influence zone.
基金Project(2014QNA50)supported by Fundamental Research Funds for the Central UniversitiesChina+1 种基金Project(51404248)supported by National Natural Science Foundation of the Youth Science Foundation of ChinaProject(PAPD)supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘A roadway within ultra-close multiple-seams(RUCMSs) is one of the most difficult supported coal roadways to deal with in underground coal mines. This is usually due to the unknown stress distributions, improper roadway layout, and unreasonable support parameters. In order to solve this support problem and effectively save RUCMSs from frequent and abrupt disasters(such as serious deformation of the surrounding rock, roof cave ins, and coal side collapse), a comprehensive method is adopted here which includes theoretical analysis, numerical simulation, and field monitoring. A mechanical model was constructed to determine the stress distribution in the coal pillar after two sides of a longwall panel had been mined. Based on this model, the horizontal, vertical, and tangential stress equations for the plane below the floor of the upper-left coal pillar were deduced. In addition, a typical coal mine(the Jinggonger colliery, located in Shuozhou city, Shanxi province, China) with an average distance between its 9# and 11# coal seams of less than 8.0 was chosen to conduct research on the proper layout and reasonable support required for a typical coal roadway located within coal seam 11#. Using FLAC3D(Fast Lagrangian Analysis of Continua in 3-Dimensions) numerical software, eight schemes were designed with different horizontal distances(d) between the center lines of the coal pillar and the roadway in the lower coal seam(RLCS). The simulations and detailed analysis indicate that the proper distances required are between 22.5 and 27.5 m. A total of 20 simulation schemes were used to investigate the factors influencing the support provided by the key bolts(bolt length, spacing, distance between two rows, installation angle, and pre-tightening force). The results were analyzed and used to determine reasonable values for the support parameters. Field results show that the stability and strength of the RLCS can be effectively safeguarded using a combination of researched stress distribution characteristics, proper layout of the RLCS, and correct support parameters.
基金supported by the Special Support Project of SASTIND and Technologyof SASTIND(No.JSZL2019XXXB001)。
文摘In order to solve the problem of reliability modeling and the analysis of complex systems with multiple closed-loop feedbacks,a new reliability analysis method for repairable systems with multiple closed-loop feedbacks is proposed based on the goal-oriented(GO)methodology.Firstly,the basic theories and advantages of GO method are introduced.Secondly,a type-24B multiple closed-loop feedback structure operator is proposed through GO method with its operation formula given,which expands the types of GO method operators and the application scope of their reliability analysis.Finally,taking a certain type of diesel engine fuel supply system an example,the quantitative and qualitative analysis is carried out through GO method,Monte Carlo simulation as well as FTA respectively.The availability results verify the availability of the proposed type-24B operator in the reliability analysis of multiple closed-loop feedback systems.The qualitative analysis results indicate the accuracy and usability of the GO method as a qualitative analysis method.
文摘Effect of multiple respiratory gas monitoring (MRGM ) on inspiredconcentration of oxygen in circult system during closed anesthesia was studied in 5l adult patients scheduled for abdominal surgery. Required flow rate of fresh oxygen (OFR), inspired oxygen concentration (FiO2 ) and oxygen saturation of pulse oximeter (SpO2) were measured continu0usly. Patients were equally divided into three groups at randorn, group C (no MRGN used ), group M, (using MRGM with its tail gas returned to circuit system), group M2 (using MRGM without tail gas returned ). The results revealed that during 180 min of closed anesthesia, OFR required in group C and M, were about 200-230 ml/min, and in group M, it was ab0ut 400 ml/min. In group C FiO2 decreased by about 10 % after 60 min of closed anesthesia (P<0. 01, 60 min vs 0 min ) and then stayed stable at this level. In group M,, FiO2 decreased by 16% at 60 min and 34 % at 180 min and the decrease was significantly greater than that in gr0up C (P<0. 01). In group Me, FiO2 remained c0nstant during closed anesthesia, which was much high(Jr than those in group C and M,. The tail gas of Capnomac Ultima MRGM contained less oxygen than its sample gas drawn fr0m circuit system simuItaneously.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX),and 81671189(to RX)。
文摘Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金Program for New Century Excellent Talents in University (NCET-10-0032)
文摘A closed-loop control allocation method is proposed for a class of aircraft with multiple actuators. Nonlinear dynamic inversion is used to design the baseline attitude controller and derive the desired moment increment. And a feedback loop for the moment increment produced by the deflections of actuators is added to the angular rate loop, then the error between the desired and actual moment increment is the input of the dynamic control allocation. Subsequently, the stability of the closed-loop dynamic control allocation system is analyzed in detail. Especially, the closedloop system stability is also analyzed in the presence of two types of actuator failures： loss of effectiveness and lock-in-place actuator failures, where a fault detection subsystem to identify the actuator failures is absent. Finally, the proposed method is applied to a canard rotor/wing （CRW） aircraft model in fixed-wing mode, which has multiple actuators for flight control. The nonlinear simulation demonstrates that this method can guarantee the stability and tracking performance whether the actuators are healthy or fail.
基金supported by the National Natural Science Foundation of China(42167068,22269020)the Gansu Province Higher Education Industry Support Plan Project(2023CYZC-68)the Central Guidance for Local Science and Technology Development Funds Project(YDZX20216200001007)。
文摘Rationally regulating the porosity of hard carbon(HC),especially the closed pores matching the low potential plateau and the ultra-microporous structure suitable for Na+embedding,has been shown to be the key to improving the sodium storage performance and initial coulombic efficiency(ICE).However,the preparation of such HC materials with specific pore structures still faces great challenges.Herein,a simple pre-oxidation strategy is employed to construct abundant closed ultra-microporous structures in soy protein powder-derived HC material,achieving a significant improvement in its ICE and platform capacity.The pre-oxidation process promotes the cross-linking degree of the soy protein,thereby hindering the directional growth of graphite domains during the carbonization process.The optimized HC exhibits ultra-high platform capacity(329 mAh g^(-1))and considerable energy density(148.5 Wh kg^(-1)).Based on the ex-situ Raman and X-ray photoelectron spectroscopy characterization results,the excellent sodium storage capacity of the HC material is attributed to the synergistic effect of adsorption-intercalation/filling.The presented work provides novel insights into the synthesis of other biomass-derived HC materials with abundant closed ultra-micro pores.
基金a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology,funded by the National Aeronautics and Space Administration and the National Science Foundation。
文摘We present the essential stellar parameters of the close visual triple system HD 2893 using Al-Wardat's method for analyzing binary and multiple star systems in conjunction with Kurucz's model atmospheres.This method accurately computes the spectrophotometric stellar masses through a combined synthetic spectral energy distribution approach that compares the results with observed data.The vigorous approach uses spectroscopic,photometric,and dynamical analysis to yield precise results.The method implements Gaia DR3 measurements and other measurements like those of Hipparcos and 2MASS All-Sky Catalog as a guide for the best fit between the synthetic spectra and observed photometry.The analysis gives precise spectrophotometric stellar masses for the system being M_(Sph)^(A)=1.20±0.07M⊙,M_(Sph)^(B)=1.09±0.06M⊙,and M_(Sph)^(C)=0.46±0.01M⊙.It shows that the three components are main sequence stars with an estimated age of around 1.0 Gyr.When integrated with the dynamical analysis,a new dynamical parallax for the system is obtained,π_(dyn)=13.8528±0.20 mas.Additionally,the discussion covers the formation and evolution of the triple system.
基金supported by Japan Society for the Promotion of Science(JSPS)Grant-in-Aid for young scientists(B)15K19984JSPS Fujita Memorial Fund for Medical Research,Takeda Science Foundation+1 种基金Uehara Memorial FoundationCentral Research Institute of Fukuoka University(No.161042)
文摘Closed-loop deep brain stimulation（DBS）：DBS has been established as a surgical therapy for movement disorders and select neuropsychiatric disorders.Various efforts to improve the clinical outcomes of the procedure have been previously made.Several factors affect the DBS clinical outcomes such as lead position,programming technique,
文摘The extended trading close(ETC)provides institutional investors an opportunity to trade at the closing price after the regular trading session(RTS)and disclosing the order imbalances to other market participants.ETCs exist in the Nasdaq,the SSE STAR,the SZSE ChiNext and the TWSE.To help a risk-averse institutional investor take advantage of the RTS and the ETC for liquidation,we develop a multistage dynamic programming model including the ETC,and derive recursive solutions for the multiple trading days scenario with closed-form solutions for the scenario with only two trading days.We also verify that the ETC is able to mitigate extreme price movements caused by fast liquidation,which is also a goal of the ETC set out by the SSE STAR and the SZSE ChiNext.Finally,we derive three results.First,an institutional investor can reduce execution costs after the introduction of the ETC.Second,a critical trading day exists,and to avoid prematurely revealing trading intentions,the investor should not trade in the ETC until such day.Third,even though the ETC orders submitted by the investor are unfilled,implementation of the ETC encourages the investor to change the liquidation strategy in the RTS,which reduces extreme price movements.In summary,the practical implications of this paper are that the investor should not trade during the ETC on the front few days to avoid prematurely revealing the investor’s trading intention by unfilled orders in the ETC and that introducing the ETC can reduce liquidation costs and extreme price movements.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by DST-FIST(Government of India)(Grant No.SR/FIST/MS-1/2017/13)and Seed Money Project(Grant No.DoRDC/733).
文摘This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.
文摘A survey of recent progress on the multiplicity and stability problems for closed characteristics on compact convex hypersurfaces in R^(2n) is given.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
