BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solel...Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solely on classification or treat segmentation and classification as separate tasks,limiting overall performance and interpretability.Methods:This study proposes an end-to-end automated framework that integrates optimized tumor localization with multiclass classification.An optimized segmentation model is first employed to generate tumor masks,which are then overlaid on MRI scans to produce attention-enhanced inputs.These inputs are subsequently used to train a convolutional neural network(CNN)classifier.Experiments were conducted on a public dataset comprising 4,237 MRI scans across four categories:normal,glioma,meningioma,and pituitary tumors.Results:Three widely used segmentation models were systematically evaluated,with an optimized U-Net achieving the best performance(accuracy=0.9939,Dice=0.8893).Segmentation-guided classification consistently improved performance across six CNN architectures,with the most notable gains observed in heterogeneous tumor types such as glioma and meningioma.Among the classifiers,EfficientNet-V2 achieved the highest performance,with an accuracy of 0.9835,precision of 0.9858,recall of 0.9804,and F1-score of 0.9828.The framework was further validated on an independent external dataset,demonstrating consistent performance and robustness across diverse MRI sources.Conclusion:The proposed framework demonstrates strong potential for multiclass brain tumor classification by effectively combining segmentation and classification.This segmentation-driven approach not only enhances predictive accuracy but also improves interpretability,making it more suitable for clinical applications.展开更多
In Alzheimer’s disease,perturbations of glutamate neurotransmission lead to synaptic dysfunction and synapse loss.Several studies have used glutamate transport inhibitors to demonstrate that soluble oligomers of amyl...In Alzheimer’s disease,perturbations of glutamate neurotransmission lead to synaptic dysfunction and synapse loss.Several studies have used glutamate transport inhibitors to demonstrate that soluble oligomers of amyloid-βinduce synaptic dysfunction by interrupting glutamate uptake mediated by glutamate transporter 1,the major glutamate transporter in the brain.The cellular targets of the synaptic effects of soluble amyloid-βoligomers,including the nature of any interaction with glutamate transporter 1,remain ill-defined.We have generated a conditional glutamate transporter 1 knockout mouse to investigate cell-type specific functions of glutamate transporter 1.Field excitatory postsynaptic potentials were examined in the CA1 region of mouse hippocampal slices.We confirmed that hippocampal long-term potentiation impairment is induced by both soluble amyloid-β oligomers and glutamate uptake inhibitors.Amyloid-βoligomers,including those isolated directly from the cortex of patients with Alzheimer’s disease,failed to inhibit hippocampal long-term potentiation in neuronal glutamate transporter 1 but not astrocytic glutamate transporter 1 knockout mice.The masking or occlusion of the effect of soluble amyloid-β oligomers by knockout of glutamate transporter 1 in neurons suggests that the metabolic or signaling consequences of knockout of glutamate transporter 1 in neurons and amyloid-βoligomer inhibition of synaptic plasticity show epistasis and thus share a similar molecular pathway.To extend these observations,we tested the effects of other types of manipulation of glutamate homeostasis on synaptic plasticity and the pathophysiology of soluble amyloid-β oligomers.Ceftriaxone,which upregulates glutamate transporter 1 levels,among other effects,prevented the impairment of long-term potentiation by soluble amyloid-β oligomers.Collectively,our findings suggest that the effects of amyloid-βon synaptic function are highly dependent on glutamate reuptake homeostasis and that the disruption of synaptic function by soluble amyloid-β oligomers is mediated by pathways linked to neuronal,not astrocytic,glutamate transporter 1.The findings of this study highlight the translational potential of targeting neuronal glutamate transporter 1 to counteract amyloid-β-induced synaptic dysfunction in Alzheimer’s disease.By showing that glutamate transporter 1 upregulation(e.g.,via ceftriaxone)can prevent amyloid-β-related impairments,this research supports developing therapies aimed at modulating glutamate homeostasis to preserve synaptic function and combat cognitive decline in patients with Alzheimer’s disease.展开更多
Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to ...Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2^(flox/flox)) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.展开更多
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Rural domestic sewage treatment is critical for environmental protection.This study defines the spatial pattern of villages from the perspective of rural sewage treatment and develops an integrated decision-making sys...Rural domestic sewage treatment is critical for environmental protection.This study defines the spatial pattern of villages from the perspective of rural sewage treatment and develops an integrated decision-making system to propose a sewage treatment mode and scheme suitable for local conditions.By considering the village spatial layout and terrain factors,a decision tree model of residential density and terrain type was constructed with accuracies of 76.47%and 96.00%,respectively.Combined with binary classification probability unit regression,an appropriate sewage treatment mode for the village was determined with 87.00%accuracy.The Analytic Hierarchy Process(AHP),combined with the Technique for Order Preference(TOPSIS)by Similarity to an Ideal Solution model,formed the basis for optimal treatment process selection under different emission standards.Verification was conducted in 542 villages across three counties of the Inner Mongolia Autonomous Region,focusing on the standard effluent effect(0.3773),low investment cost(0.3196),and high standard effluent effect(0.5115)to determine the best treatment process for the same emission standard under different needs.The annual environmental and carbon emission benefits of sewage treatment in these villages were estimated.This model matches village density,geographic feature,and social development level,and provides scientific support and a theoretical basis for rural sewage treatment decision-making.展开更多
Based on the Smit-Suhl formula,we propose a universal approach for solving the magnon-magnon coupling problem in bilayer coupled systems(e.g.,antiferromagnets).This method requires only the energy expression,enabling ...Based on the Smit-Suhl formula,we propose a universal approach for solving the magnon-magnon coupling problem in bilayer coupled systems(e.g.,antiferromagnets).This method requires only the energy expression,enabling the automatic derivation of analytical expressions for the eigenmatrix elements via symbolic computation,eliminating the need for tedious manual calculations.Using this approach,we investigate the impact of magnetic hysteresis on magnon-magnon coupling in a system with interlayer Dzyaloshinskii-Moriya interaction(DMI).The magnetic hysteresis leads to an asymmetric magnetic field dependence of the resonance frequency and alters the number of degeneracy points between the pure optical and acoustic modes.Moreover,it can result in the coupling strength at the gap of the f–H phase diagram being nearly vanishing,contrary to the conventionally expected maximum.These results deepen the understanding of the effect of interlayer DMI on magnon–magnon coupling and the proposed universal method significantly streamlines the solving process of magnon–magnon coupling problems.展开更多
AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study pr...critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study proposes a non-invasive approach using digital mammography images and deep learning algorithm for classifying breast cancer molecular subtypes.Four pretrained models,including two Convolutional Neural Networks(MobileNet_V3_Large and VGG-16)and two Vision Transformers(ViT_B_16 and ViT_Base_Patch16_Clip_224)were fine-tuned to classify images into HER2-enriched,Luminal,Normal-like,and Triple Negative subtypes.Hyperparameter tuning,including learning rate adjustment and layer freezing strategies,was applied to optimize performance.Among the evaluated models,ViT_Base_Patch16_Clip_224 achieved the highest test accuracy(94.44%),with equally high precision,recall,and F1-score of 0.94,demonstrating excellent generalization.MobileNet_V3_Large achieved the same accuracy but showed less training stability.In contrast,VGG-16 recorded the lowest performance,indicating a limitation in its generalizability for this classification task.The study also highlighted the superior performance of the Vision Transformer models over CNNs,particularly due to their ability to capture global contextual features and the benefit of CLIP-based pretraining in ViT_Base_Patch16_Clip_224.To enhance clinical applicability,a graphical user interface(GUI)named“BCMS Dx”was developed for streamlined subtype prediction.Deep learning applied to mammography has proven effective for accurate and non-invasive molecular subtyping.The proposed Vision Transformer-based model and supporting GUI offer a promising direction for augmenting diagnostic workflows,minimizing the need for invasive procedures,and advancing personalized breast cancer management.展开更多
BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant rec...BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to use...This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.展开更多
Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited...Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited effects on slowing down disease progression or biomarkers.Despite numerous successful preclinical analyses,most new drugs fail when translated to clinical trials(Petrov et al.,2017).This is believed to be,in part,due to the multilayer heterogeneity of ALS(e.g.,clinical,genetic,and molecular;Tzeplaeff et al.,2024).Studies integrating multi-omic data are still limited,making it difficult to fully understand the biological complexity that characterizes the disease.展开更多
Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhyt...Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhythm of 100-120 times/min for CC.[1,2]Interruptions of the CC must be as short as possible and are related to ventilation,defibrillation and turnover of the rescuers.Most of the automated external defibrillators(AEDs)require interruptions of the CC to perform rhythm analysis.Among the numerous marketed models of AEDs,some provide real-time feedback about the quality of the CC.展开更多
The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in S...The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.展开更多
Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential a...Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control.This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus(T2DM)receiving A+B therapy.Methods:This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE(Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma)dataset across 18 Italian centres(May 2020-January 2024).We evaluated objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and time to progression(TTP)using Cox regression analysis and Inverse Probability of Treatment Weighting(IPTW)to address confounding.Results:Among 523 patients,341(65.2%)did not have diabetes and 182(34.8%)had T2DM.In the overall population,metformin showed no significant benefit for PFS(HR=1.15,95%CI[0.88-1.50],p=0.316)or OS(HR=1.28,95%CI[0.94-1.74],p=0.124).In the subgroup with T2DM(N=180),metformin showed no significant benefit for PFS(HR=1.41,95%CI[0.97-2.05],p=0.069),OS(HR=1.23,95%CI[0.81-1.86],p=0.333),or TTP(HR=0.82,95%CI[0.53-1.26],p=0.363).IPTW analysis confirmed these negative findings.Conclusion:This study found no evidence of improved outcomes with metformin use in patients with HCC in particular with T2DM receiving A+B therapy.Routine metformin use should not be expected to enhance A+B efficacy based on current evidence.展开更多
This study proposes a multi-scale simplified residual convolutional neural network(MS-SRCNN)for the precise prediction of Mg-Nd binary alloy compositions from scanning electron microscope(SEM)images.A multi-scale data...This study proposes a multi-scale simplified residual convolutional neural network(MS-SRCNN)for the precise prediction of Mg-Nd binary alloy compositions from scanning electron microscope(SEM)images.A multi-scale data structure is established by spatially aligning and stacking SEM images at different magnifications.The MS-SRCNN significantly reduces computational runtime by over 90%compared to traditional architectures like ResNet50,VGG16,and VGG19,without compromising prediction accuracy.The model demonstrates more excellent predictive performance,achieving a>5%increase in R^(2) compared to single-scale models.Furthermore,the MS-SRCNN exhibits robust composition prediction capability across other Mg-based binary alloys,including Mg-La,Mg-Sn,Mg-Ce,Mg-Sm,Mg-Ag,and Mg-Y,thereby emphasizing its generalization and extrapolation potential.This research establishes a non-destructive,microstructure-informed composition analysis framework,reduces characterization time compared to traditional experiment methods and provides insights into the composition-microstructure relationship in diverse material systems.展开更多
α-MnO_(2) is a promising,inexpensive,and readily producible catalyst for the oxygen reduction reaction(ORR)in alkaline media,but its application is limited by low electronic conductivity.In this study,we enhance the ...α-MnO_(2) is a promising,inexpensive,and readily producible catalyst for the oxygen reduction reaction(ORR)in alkaline media,but its application is limited by low electronic conductivity.In this study,we enhance the performance ofα-MnO_(2) electrodes by systematically varying theα-MnO_(2)-to-Vulcan ratio within the catalyst layer.Electrodes are evaluated in a gas diffusion electrode(GDE)half-cell,where an optimized catalyst layer composition leads to significantly improved ORR performance.By finetuning both theα-MnO_(2)-to-Vulcan ratio and theα-MnO_(2) loading,the electrode outperforms a commercial MnO_(2)-based electrode and approaches the performance of the Pt/C benchmark.The improvement is attributed to the presence of a three-dimensional(3D)Vulcan network electronically connecting catalytically activeα-MnO_(2) sites with the substrate.Additionally,the optimized electrodes are employed in a prototype Al-O_(2) flow cell.Under constant oxygen flow,power densities exceed 250 mW cm^(-2),which is significantly higher than that of conventional Al-air batteries.Electrochemical impedance spectroscopy combined with distribution of relaxation times(DRT)analysis enables the separation of anode and cathode charge transfer impedances without the need for an additional reference electrode.The analysis reveals that the anode contributes more than twice as much impedance as the cathode,highlighting the need for further anode optimization.This work demonstrates a transferable approach for catalyst layer screening under technically relevant conditions in the GDE half-cell.Subsequent measurements in an Al-O_(2) flow cell validate the approach.The methodology is widely applicable to the development of advanced electrodes for a variety of metal-air battery technologies.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk ...Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.展开更多
Renal cell carcinoma(RCC)is a challenging urologic malignancy characterized by its aggressive nature,including invasion,metastasis,and treatment resistance.To explore multi-targeted therapies,we established an advance...Renal cell carcinoma(RCC)is a challenging urologic malignancy characterized by its aggressive nature,including invasion,metastasis,and treatment resistance.To explore multi-targeted therapies,we established an advanced clear cell renal cell carcinoma(cc RCC)model via orthotopic tumor transplantation in mice,and established another model simulating post-surgical recurrence by performing radical nephrectomy.We engineered a genetic circuit to reprogram the host liver as a bioreactor,enabling the production and delivery of in vivo self-assembled si RNAs(IVSA-si RNAs)for co-targeting VEGFR2 and m TOR.The efficacy and toxicity of this IVSA-si RNA system were evaluated and compared with the combination therapy of sunitinib and everolimus.In the established models,the combination therapy of sunitinib and everolimus showed efficacy but induced severe adverse effects.In contrast,IVSA-si RNAs potently silenced VEGFR2 and m TOR expression,achieving therapeutic effects in both advanced and radical nephrectomy cc RCC models without discernible toxicity.展开更多
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
文摘Background:Accurate classification of brain tumors from Magnetic Resonance Imaging(MRI)is essential for clinical decision-making but remains challenging due to tumor heterogeneity.Existing approaches often focus solely on classification or treat segmentation and classification as separate tasks,limiting overall performance and interpretability.Methods:This study proposes an end-to-end automated framework that integrates optimized tumor localization with multiclass classification.An optimized segmentation model is first employed to generate tumor masks,which are then overlaid on MRI scans to produce attention-enhanced inputs.These inputs are subsequently used to train a convolutional neural network(CNN)classifier.Experiments were conducted on a public dataset comprising 4,237 MRI scans across four categories:normal,glioma,meningioma,and pituitary tumors.Results:Three widely used segmentation models were systematically evaluated,with an optimized U-Net achieving the best performance(accuracy=0.9939,Dice=0.8893).Segmentation-guided classification consistently improved performance across six CNN architectures,with the most notable gains observed in heterogeneous tumor types such as glioma and meningioma.Among the classifiers,EfficientNet-V2 achieved the highest performance,with an accuracy of 0.9835,precision of 0.9858,recall of 0.9804,and F1-score of 0.9828.The framework was further validated on an independent external dataset,demonstrating consistent performance and robustness across diverse MRI sources.Conclusion:The proposed framework demonstrates strong potential for multiclass brain tumor classification by effectively combining segmentation and classification.This segmentation-driven approach not only enhances predictive accuracy but also improves interpretability,making it more suitable for clinical applications.
文摘In Alzheimer’s disease,perturbations of glutamate neurotransmission lead to synaptic dysfunction and synapse loss.Several studies have used glutamate transport inhibitors to demonstrate that soluble oligomers of amyloid-βinduce synaptic dysfunction by interrupting glutamate uptake mediated by glutamate transporter 1,the major glutamate transporter in the brain.The cellular targets of the synaptic effects of soluble amyloid-βoligomers,including the nature of any interaction with glutamate transporter 1,remain ill-defined.We have generated a conditional glutamate transporter 1 knockout mouse to investigate cell-type specific functions of glutamate transporter 1.Field excitatory postsynaptic potentials were examined in the CA1 region of mouse hippocampal slices.We confirmed that hippocampal long-term potentiation impairment is induced by both soluble amyloid-β oligomers and glutamate uptake inhibitors.Amyloid-βoligomers,including those isolated directly from the cortex of patients with Alzheimer’s disease,failed to inhibit hippocampal long-term potentiation in neuronal glutamate transporter 1 but not astrocytic glutamate transporter 1 knockout mice.The masking or occlusion of the effect of soluble amyloid-β oligomers by knockout of glutamate transporter 1 in neurons suggests that the metabolic or signaling consequences of knockout of glutamate transporter 1 in neurons and amyloid-βoligomer inhibition of synaptic plasticity show epistasis and thus share a similar molecular pathway.To extend these observations,we tested the effects of other types of manipulation of glutamate homeostasis on synaptic plasticity and the pathophysiology of soluble amyloid-β oligomers.Ceftriaxone,which upregulates glutamate transporter 1 levels,among other effects,prevented the impairment of long-term potentiation by soluble amyloid-β oligomers.Collectively,our findings suggest that the effects of amyloid-βon synaptic function are highly dependent on glutamate reuptake homeostasis and that the disruption of synaptic function by soluble amyloid-β oligomers is mediated by pathways linked to neuronal,not astrocytic,glutamate transporter 1.The findings of this study highlight the translational potential of targeting neuronal glutamate transporter 1 to counteract amyloid-β-induced synaptic dysfunction in Alzheimer’s disease.By showing that glutamate transporter 1 upregulation(e.g.,via ceftriaxone)can prevent amyloid-β-related impairments,this research supports developing therapies aimed at modulating glutamate homeostasis to preserve synaptic function and combat cognitive decline in patients with Alzheimer’s disease.
基金supported by an NIH grant R01 DE031413 (M.V.B.)。
文摘Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2^(flox/flox)) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
基金supported by the Central Government Guiding Local Science and Technology Development Fund Project(No.2024SZY0343)the Joint Research Program for Ecological Conservation and High Quality Development of the Yellow River Basin(No.2022-YRUC-01-050205)+2 种基金the Higher Education Scientific Research Project of Inner Mongolia Autonomous Region(No.NJZZ23078)the project of Inner Mongolia"Prairie Talents"Engineering Innovation Entrepreneurship Talent Team,the Major Projects of Erdos Science and Technology(No.2022EEDSKJZDZX015)the Innovation Team of the Inner Mongolia Academy of Science and Technology(No.CXTD2023-01-016).
文摘Rural domestic sewage treatment is critical for environmental protection.This study defines the spatial pattern of villages from the perspective of rural sewage treatment and develops an integrated decision-making system to propose a sewage treatment mode and scheme suitable for local conditions.By considering the village spatial layout and terrain factors,a decision tree model of residential density and terrain type was constructed with accuracies of 76.47%and 96.00%,respectively.Combined with binary classification probability unit regression,an appropriate sewage treatment mode for the village was determined with 87.00%accuracy.The Analytic Hierarchy Process(AHP),combined with the Technique for Order Preference(TOPSIS)by Similarity to an Ideal Solution model,formed the basis for optimal treatment process selection under different emission standards.Verification was conducted in 542 villages across three counties of the Inner Mongolia Autonomous Region,focusing on the standard effluent effect(0.3773),low investment cost(0.3196),and high standard effluent effect(0.5115)to determine the best treatment process for the same emission standard under different needs.The annual environmental and carbon emission benefits of sewage treatment in these villages were estimated.This model matches village density,geographic feature,and social development level,and provides scientific support and a theoretical basis for rural sewage treatment decision-making.
基金supported by the National Key Research and Development Program of China (MOST)(Grant No.2022YFA1402800)the Chinese Academy of Sciences (CAS) Presidents International Fellowship Initiative (PIFI)(Grant No.2025PG0006)+3 种基金the National Natural Science Foundation of China (NSFC)(Grant Nos.51831012,12274437,and 52161160334)the CAS Project for Young Scientists in Basic Research (Grant No.YSBR-084)the CAS Youth Interdisciplinary Teamthe China Postdoctoral Science Foundation (Grant No.2025M773402)。
文摘Based on the Smit-Suhl formula,we propose a universal approach for solving the magnon-magnon coupling problem in bilayer coupled systems(e.g.,antiferromagnets).This method requires only the energy expression,enabling the automatic derivation of analytical expressions for the eigenmatrix elements via symbolic computation,eliminating the need for tedious manual calculations.Using this approach,we investigate the impact of magnetic hysteresis on magnon-magnon coupling in a system with interlayer Dzyaloshinskii-Moriya interaction(DMI).The magnetic hysteresis leads to an asymmetric magnetic field dependence of the resonance frequency and alters the number of degeneracy points between the pure optical and acoustic modes.Moreover,it can result in the coupling strength at the gap of the f–H phase diagram being nearly vanishing,contrary to the conventionally expected maximum.These results deepen the understanding of the effect of interlayer DMI on magnon–magnon coupling and the proposed universal method significantly streamlines the solving process of magnon–magnon coupling problems.
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
基金funded by the Ministry of Higher Education(MoHE)Malaysia through the Fundamental Research Grant Scheme—Early Career Researcher(FRGS-EC),grant number FRGSEC/1/2024/ICT02/UNIMAP/02/8.
文摘critical for guiding treatment and improving patient outcomes.Traditional molecular subtyping via immuno-histochemistry(IHC)test is invasive,time-consuming,and may not fully represent tumor heterogeneity.This study proposes a non-invasive approach using digital mammography images and deep learning algorithm for classifying breast cancer molecular subtypes.Four pretrained models,including two Convolutional Neural Networks(MobileNet_V3_Large and VGG-16)and two Vision Transformers(ViT_B_16 and ViT_Base_Patch16_Clip_224)were fine-tuned to classify images into HER2-enriched,Luminal,Normal-like,and Triple Negative subtypes.Hyperparameter tuning,including learning rate adjustment and layer freezing strategies,was applied to optimize performance.Among the evaluated models,ViT_Base_Patch16_Clip_224 achieved the highest test accuracy(94.44%),with equally high precision,recall,and F1-score of 0.94,demonstrating excellent generalization.MobileNet_V3_Large achieved the same accuracy but showed less training stability.In contrast,VGG-16 recorded the lowest performance,indicating a limitation in its generalizability for this classification task.The study also highlighted the superior performance of the Vision Transformer models over CNNs,particularly due to their ability to capture global contextual features and the benefit of CLIP-based pretraining in ViT_Base_Patch16_Clip_224.To enhance clinical applicability,a graphical user interface(GUI)named“BCMS Dx”was developed for streamlined subtype prediction.Deep learning applied to mammography has proven effective for accurate and non-invasive molecular subtyping.The proposed Vision Transformer-based model and supporting GUI offer a promising direction for augmenting diagnostic workflows,minimizing the need for invasive procedures,and advancing personalized breast cancer management.
文摘BACKGROUND The use of induction immunosuppression agents has improved kidney transplant outcomes,but selecting the optimal agent remains a point of debate.AIM To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction,focusing on graft function,acute rejection,infection,malignancy,post-transplant glomerulonephritis,and survival,using a propensity score matched cohort design.METHODS Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated.Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts.Baseline characteristics,immunosuppression regimens,and outcomes were analyzed.Linear,binary logistic and Cox proportional hazard regression models.RESULTS A total of 436 recipients were included,with a median follow-up of 5.2 years.The matched cohort(n=262)had a mean age of 51.1±13.5 years;39%were female and 92%were white.There was no significant difference in the cumulative incidence of acute rejection[odds ratio(OR)=2.10;95%CI:0.9-4.9;P=0.110].Compared with basiliximab,alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months(-6.6 mL/minute/1.73 m2;95%CI:-10.5 to-2.7;P<0.001)and higher risks of cytomegalovirus viremia(OR=3.2;95%CI:1.6-6.5;P<0.001),BK viremia(OR=2.4;95%CI:1.1-5.5;P=0.02),post-transplant malignancy(OR=6.2;95%CI:1.6-29.9;P=0.013),and death-censored graft loss(hazard ratio=3.6;95%CI:1.2-11.4;P=0.03).No significant differences were observed in post-transplant glomerulonephritis or recipient mortality.CONCLUSION In this propensity score-matched analysis,alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection,post-transplant malignancy,and graft loss compared with basiliximab.These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
基金funded by the Office of the Vice-President for Research and Development of Cebu Technological University.
文摘This study demonstrates a novel integration of large language models,machine learning,and multicriteria decision-making to investigate self-moderation in small online communities,a topic under-explored compared to user behavior and platform-driven moderation on social media.The proposed methodological framework(1)utilizes large language models for social media post analysis and categorization,(2)employs k-means clustering for content characterization,and(3)incorporates the TODIM(Tomada de Decisão Interativa Multicritério)method to determine moderation strategies based on expert judgments.In general,the fully integrated framework leverages the strengths of these intelligent systems in a more systematic evaluation of large-scale decision problems.When applied in social media moderation,this approach promotes nuanced and context-sensitive self-moderation by taking into account factors such as cultural background and geographic location.The application of this framework is demonstrated within Facebook groups.Eight distinct content clusters encompassing safety,harassment,diversity,and misinformation are identified.Analysis revealed a preference for content removal across all clusters,suggesting a cautious approach towards potentially harmful content.However,the framework also highlights the use of other moderation actions,like account suspension,depending on the content category.These findings contribute to the growing body of research on self-moderation and offer valuable insights for creating safer and more inclusive online spaces within smaller communities.
文摘Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited effects on slowing down disease progression or biomarkers.Despite numerous successful preclinical analyses,most new drugs fail when translated to clinical trials(Petrov et al.,2017).This is believed to be,in part,due to the multilayer heterogeneity of ALS(e.g.,clinical,genetic,and molecular;Tzeplaeff et al.,2024).Studies integrating multi-omic data are still limited,making it difficult to fully understand the biological complexity that characterizes the disease.
文摘Basic life support for cardiac arrest associates cardiopulmonary resuscitation(CPR)and defibrillation.CPR relies on chest compressions(CC)and ventilation.Current guidelines on CPR recommend a depth of 5-6 cm at a rhythm of 100-120 times/min for CC.[1,2]Interruptions of the CC must be as short as possible and are related to ventilation,defibrillation and turnover of the rescuers.Most of the automated external defibrillators(AEDs)require interruptions of the CC to perform rhythm analysis.Among the numerous marketed models of AEDs,some provide real-time feedback about the quality of the CC.
基金the research project LaTe4PoliticES(PID2022-138099OB-I00)funded by MCIN/AEI/10.13039/501100011033 and the European Fund for Regional Development(ERDF)-a way to make Europe.Tomás Bernal-Beltrán is supported by University of Murcia through the predoctoral programme.
文摘The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.
文摘Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control.This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus(T2DM)receiving A+B therapy.Methods:This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE(Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma)dataset across 18 Italian centres(May 2020-January 2024).We evaluated objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and time to progression(TTP)using Cox regression analysis and Inverse Probability of Treatment Weighting(IPTW)to address confounding.Results:Among 523 patients,341(65.2%)did not have diabetes and 182(34.8%)had T2DM.In the overall population,metformin showed no significant benefit for PFS(HR=1.15,95%CI[0.88-1.50],p=0.316)or OS(HR=1.28,95%CI[0.94-1.74],p=0.124).In the subgroup with T2DM(N=180),metformin showed no significant benefit for PFS(HR=1.41,95%CI[0.97-2.05],p=0.069),OS(HR=1.23,95%CI[0.81-1.86],p=0.333),or TTP(HR=0.82,95%CI[0.53-1.26],p=0.363).IPTW analysis confirmed these negative findings.Conclusion:This study found no evidence of improved outcomes with metformin use in patients with HCC in particular with T2DM receiving A+B therapy.Routine metformin use should not be expected to enhance A+B efficacy based on current evidence.
基金funded by the National Natural Science Foundation of China(No.52204407)the Natural Science Foundation of Jiangsu Province(No.BK20220595)the China Postdoctoral Science Foundation(No.2022M723689).
文摘This study proposes a multi-scale simplified residual convolutional neural network(MS-SRCNN)for the precise prediction of Mg-Nd binary alloy compositions from scanning electron microscope(SEM)images.A multi-scale data structure is established by spatially aligning and stacking SEM images at different magnifications.The MS-SRCNN significantly reduces computational runtime by over 90%compared to traditional architectures like ResNet50,VGG16,and VGG19,without compromising prediction accuracy.The model demonstrates more excellent predictive performance,achieving a>5%increase in R^(2) compared to single-scale models.Furthermore,the MS-SRCNN exhibits robust composition prediction capability across other Mg-based binary alloys,including Mg-La,Mg-Sn,Mg-Ce,Mg-Sm,Mg-Ag,and Mg-Y,thereby emphasizing its generalization and extrapolation potential.This research establishes a non-destructive,microstructure-informed composition analysis framework,reduces characterization time compared to traditional experiment methods and provides insights into the composition-microstructure relationship in diverse material systems.
基金part of the ALU-STORE project(Aluminum Metal as Energy Carrier for Seasonal Energy Storage)funded by the KIT Future Fieldsthe research performed at CELEST(Center for Electrochemical Energy Storage Ulm-Karlsruhe)+1 种基金funding from the German Federal Ministry of Research,Technology and Space(BMFTR)in the Nano Mat Futur program(03XP0423)basic funding from the Helmholtz Association。
文摘α-MnO_(2) is a promising,inexpensive,and readily producible catalyst for the oxygen reduction reaction(ORR)in alkaline media,but its application is limited by low electronic conductivity.In this study,we enhance the performance ofα-MnO_(2) electrodes by systematically varying theα-MnO_(2)-to-Vulcan ratio within the catalyst layer.Electrodes are evaluated in a gas diffusion electrode(GDE)half-cell,where an optimized catalyst layer composition leads to significantly improved ORR performance.By finetuning both theα-MnO_(2)-to-Vulcan ratio and theα-MnO_(2) loading,the electrode outperforms a commercial MnO_(2)-based electrode and approaches the performance of the Pt/C benchmark.The improvement is attributed to the presence of a three-dimensional(3D)Vulcan network electronically connecting catalytically activeα-MnO_(2) sites with the substrate.Additionally,the optimized electrodes are employed in a prototype Al-O_(2) flow cell.Under constant oxygen flow,power densities exceed 250 mW cm^(-2),which is significantly higher than that of conventional Al-air batteries.Electrochemical impedance spectroscopy combined with distribution of relaxation times(DRT)analysis enables the separation of anode and cathode charge transfer impedances without the need for an additional reference electrode.The analysis reveals that the anode contributes more than twice as much impedance as the cathode,highlighting the need for further anode optimization.This work demonstrates a transferable approach for catalyst layer screening under technically relevant conditions in the GDE half-cell.Subsequent measurements in an Al-O_(2) flow cell validate the approach.The methodology is widely applicable to the development of advanced electrodes for a variety of metal-air battery technologies.
基金supported by the National Key Research and Development Program(2024YFA1307101).
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is now considered to be among the most prevalent chronic liver diseases worldwide.Its comprehensive management encompasses multiple stages,including risk assessment,early detection,stratified intervention,and long-term follow-up.Among these,improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice.In recent years,artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field,offering novel tools and pathways for MASLD risk stratification,non-invasive diagnosis,therapeutic evaluation,and patient self-management.This review summarizes the current applications of artificial intelligence and smart devices in MASLD care,highlights their benefits and limitations,and discusses future directions to support precision diagnosis and treatment strategies.
基金supported by grants from the National Natural Science Foundation of China(No.32022015,31871295 and 82373158)the Training Program of the Major Research Plan of the National Natural Science Foundation of China(No.92268120)+1 种基金the Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study(No.SN-ZJU-SIAS-008)CAMS Innovation Fund for Medical Sciences(No.CIFMS-2021-I2M-5–015)。
文摘Renal cell carcinoma(RCC)is a challenging urologic malignancy characterized by its aggressive nature,including invasion,metastasis,and treatment resistance.To explore multi-targeted therapies,we established an advanced clear cell renal cell carcinoma(cc RCC)model via orthotopic tumor transplantation in mice,and established another model simulating post-surgical recurrence by performing radical nephrectomy.We engineered a genetic circuit to reprogram the host liver as a bioreactor,enabling the production and delivery of in vivo self-assembled si RNAs(IVSA-si RNAs)for co-targeting VEGFR2 and m TOR.The efficacy and toxicity of this IVSA-si RNA system were evaluated and compared with the combination therapy of sunitinib and everolimus.In the established models,the combination therapy of sunitinib and everolimus showed efficacy but induced severe adverse effects.In contrast,IVSA-si RNAs potently silenced VEGFR2 and m TOR expression,achieving therapeutic effects in both advanced and radical nephrectomy cc RCC models without discernible toxicity.
