The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-born...Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.展开更多
This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic ...This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic reproductive number R0 is proved, which determines whether the plant disease will be extinct or not. If R0 R0 > 1 , there exists a unique endemic equilibrium which is globally stable. The numerical simulations are provided to verify our theoretical results, which indicate that after infective individuals reach some level, strengthening treatment measures is proved to be beneficial in controlling disease transmission.展开更多
Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequence...Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.展开更多
Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrog...Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.展开更多
AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surfa...AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patie...BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.展开更多
BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram...BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.展开更多
Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying m...Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.展开更多
BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to b...Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.展开更多
BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To...BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.展开更多
The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although v...The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.展开更多
Multiorgan-on-a-chip(MOoC)systems are advanced microfluidic devices that integrate multiple organ models into a single modular unit,each composed of cells derived from various tissues or organs.These systems enable in...Multiorgan-on-a-chip(MOoC)systems are advanced microfluidic devices that integrate multiple organ models into a single modular unit,each composed of cells derived from various tissues or organs.These systems enable interorgan communication and accurately replicate physiological conditions,providing a more physiologically relevant modeling framework for constructing disease models and predicting drug efficacy and toxicity.MOoC systems also provide significant advantages in terms of flexibility,cost-effectiveness,and reproducibility,making them valuable tools for drug development and toxicity assessment.In this review,we first provide an overview of the MOoC technology,covering cell sources,stimulations,materials and fabrication techniques,and biosensors.We then examine the application of MOoC systems in disease modeling,focusing on cancer metastasis,metabolic disorders,and cardiovascular disease.We next discuss the use of MOoC systems in drug toxicity evaluation and drug screening,emphasizing their role in providing comprehensive assessments of drug effects.Finally,we address the challenges it faces and the future perspectives of the MOoC technology.展开更多
Objective:To analyze the impact and mechanism of the SOC model intervention on improving health literacy and reducing disease uncertainty among young and middle-aged patients with coronary heart disease.Methods:A hund...Objective:To analyze the impact and mechanism of the SOC model intervention on improving health literacy and reducing disease uncertainty among young and middle-aged patients with coronary heart disease.Methods:A hundred young and middle-aged patients with coronary heart disease from our hospital between March and October 2024 were randomly divided into an observation group and a control group,with 50 patients in each group.Both groups received routine nursing intervention,while the observation group also received intervention based on the Stages of Change(SOC)model.The intervention period was 30 days.Changes in self-efficacy,health literacy,and disease uncertainty were compared between the two groups before and after the intervention.Results:After the intervention,the self-efficacy scores of both groups increased significantly,and the observation group had higher self-efficacy scores than the control group,with a significant difference(P<0.05).Additionally,the observation group showed significantly higher levels of health literacy than the control group(P<0.001).Furthermore,the observation group had significantly lower scores for disease uncertainty compared to the control group(P<0.001).Conclusion:The SOC model,in addition to routine nursing,significantly affects self-efficacy,disease uncertainty,and health literacy among young and middle-aged patients with coronary heart disease.It helps to enhance patients’knowledge of coronary heart disease,improve health literacy levels,and reduce disease uncertainty,making it worthy of clinical promotion and application.展开更多
AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of oph...AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.展开更多
BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whethe...BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.展开更多
The frequent outbreaks of crop diseases pose a serious threat to global agricultural production and food security.Data-driven forecasting models have emerged as an effective approach to support early warning and manag...The frequent outbreaks of crop diseases pose a serious threat to global agricultural production and food security.Data-driven forecasting models have emerged as an effective approach to support early warning and management,yet the lack of user-friendly tools for model development remains a major bottleneck.This study presents the Multi-Scenario Crop Disease Forecasting Modeling System(MSDFS),an open-source platform that enables end-to-end model construction-from multi-source data ingestion and feature engineering to training,evaluation,and deployment-across four representative scenarios:static point-based,static grid-based,dynamic point-based,and dynamic grid-based.Unlike conventional frameworks,MSDFS emphasizes modeling flexibility,allowing users to build,compare,and interpret diverse forecasting approaches within a unified workflow.A notable feature of the system is the integration of a weather scenario generator,which facilitates comprehensive testing of model performance and adaptability under extreme climatic conditions.Case studies corresponding to the four scenarios were used to validate the system,with overall accuracy(OA)ranging from 73%to 93%.By lowering technical barriers,the system is designed to serve plant protection managers and agricultural producers without advanced programming expertise,providing a practical modeling tool that supports the construction of smart plant protection systems.展开更多
BACKGROUND Gastrointestinal diseases have complex etiologies and clinical presentations.An accurate diagnosis requires physicians to integrate diverse information,including medical history,laboratory test results,and ...BACKGROUND Gastrointestinal diseases have complex etiologies and clinical presentations.An accurate diagnosis requires physicians to integrate diverse information,including medical history,laboratory test results,and imaging findings.Existing artificial intelligence-assisted diagnostic tools are limited to single-modality information,resulting in recommendations that are often incomplete and may be associated with clinical or legal risks.AIM To develop and evaluate a collaborative multimodal large language model(LLM)framework for clinical decision-making in digestive diseases.METHODS In this observational study,DeepGut,a multimodal LLM collaborative diagnostic framework,was developed to integrate four distinct large models into a four-tiered structure.The framework sequentially accomplishes multimodal infor-mation extraction,logical“chain”construction,diagnostic and treatment suggestion generation,and risk analysis.The model was evaluated using objective metrics,which assess the reliability and comprehensiveness of model-generated results,and subjective expert opinions,which examine the effectiveness of the framework in assisting physicians.RESULTS The diagnostic and treatment recommendations generated by the DeepGut framework achieved exceptional performance,with a diagnostic accuracy of 97.8%,diagnostic completeness of 93.9%,treatment plan accuracy of 95.2%,and treatment plan completeness of 98.0%,significantly surpassing the capabilities of single-modal LLM-based diagnostic tools.Experts evaluating the framework commended the completeness,relevance,and logical coherence of its outputs.However,the collaborative multimodal LLM approach resulted in increased input and output token counts,leading to higher computational costs and extended diagnostic times.CONCLUSION The framework achieves successful integration of multimodal diagnostic data,demonstrating enhanced performance enabled by multimodal LLM collaboration,which opens new horizons for the clinical application of artificial intelligence-assisted technology.展开更多
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
文摘Background: Social determinants of health (SDOH) significantly influence diseases with environmental components, like vector-borne parasitic diseases. This study aims to examine how these factors influence vector-borne parasitic diseases (VBPDs) transmission in Chad and provide recommendations for policy improvements. Methods: The study adopts the WHO Conceptual Framework of SDOH to compare two regions in Southern Chad: Kouh-Est, which has an ongoing vector control program, and Grand-Sido, which lacks such a program. The study includes both nomadic and sedentary populations to provide a comprehensive understanding of the SDOH influencing VBPDs. Households were randomly selected. Data on sociodemographic characteristics, literacy, knowledge of VBPDs and protective measures, and access to education and health facilities were collected. Results: A total of 202 households from 17 villages, including 820 participants, were surveyed. Agriculture, livestock, and fishing were the main occupations, involving 84.1% of participants. Literacy was low, with 36.7% non-educated, 47.7% completing primary school, 14.5% secondary school, and only 0.3% reaching tertiary education. Most villages lacked schools beyond the primary level, and nomadic populations were significantly less educated than sedentary ones (p Conclusion: Educational deficiencies, lack of protective measures against vectors, inadequate healthcare resources, and lifestyle conditions aggravated by poor road infrastructure, limited transportation, and economic constraints contribute to worsened VBPDs outcomes in these rural populations. Addressing these systemic issues in the surveyed communities is essential for improving health equity and VBPDs outcomes in these regions specifically and in similar populations settings more broadly.
文摘This paper proposes a vector-borne plant disease model with discontinuous treatment strategies. Constructing Lyapunov function and applying non-smooth theory to analyze discontinuous differential equations, the basic reproductive number R0 is proved, which determines whether the plant disease will be extinct or not. If R0 R0 > 1 , there exists a unique endemic equilibrium which is globally stable. The numerical simulations are provided to verify our theoretical results, which indicate that after infective individuals reach some level, strengthening treatment measures is proved to be beneficial in controlling disease transmission.
文摘Vector-borne diseases are highly sensitive to environment and to environmental changes. Rift Valley Fever (RFV) is a mosquito-borne zootic virus associated with severe diseases in human beings and economic consequences to livestock sector. Animal and human movements have a fundamental impact on RVF transmission. In recent years, there has been a growing interest in the use of mathematics and agent based models to represent and analyze the dynamic of RFV transmission. However, no previous study has taken into consideration animal herds’ mobility and precipitation factors to understand the disease spread. This limitation underlines the necessity to use computational model approach based on multi-agent system in the study of vector-borne diseases transmission and diffusion. In this paper, a multi-agent system combining conceptual model expressiveness is used to study animal herds’ mobility and the precipitation parameter impact on the Rift Valley Fever outbreak in Ferlo Barkedji in Northern Senegal. Simulation scenarios with various parameters, including rain quality, hosts, vectors, camp dispersal around ponds, etc., are unrolled. The different results we have obtained show that the evolution of the number of infected hosts and infected vectors depend on the degree of animal herds’ mobility and on precipitations. Our model provides a framework that permits predicting the spread of the disease associated with the mobility of animal herds.
基金supported by the National Research Foundation of Korea (NRF)funded by the Ministry of Science,ICT&Future Planning (2022R1A2C2006229,2022R1A6A3A01086868)Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)funded by the Ministry of Health&Welfare and Ministry of Science and ICT,Republic of Korea (RS-2024-00345328)KIST Institutional Grant (2E32851)。
文摘Alzheimer'sdisease(AD)isaprogressive neurodegenerative disorder characterized by cognitive impairment and distinct neuropathological features,including amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis.Developing effective diagnostic,preventative,and therapeutic strategies for AD necessitates the establishment of animal models that accurately recapitulate the pathophysiological processes of the disease.Existing transgenic mouse models have significantly contributed to understanding AD pathology but often fail to replicate the complexity of human AD.Additionally,these models are limited in their ability to elucidate the interplay among amyloid-βplaques,neurofibrillary tangles,and reactive astrogliosis due to the absence of spatially and temporally specific genetic manipulation.In this study,we introduce a novel AD mouse model(APP/PS1-TauP301L-Adeno mice)designed to rapidly induce pathological symptoms and enhance understanding of AD mechanisms.Neurofibrillary tangles and severe reactive astrogliosis were induced by injecting AAVDJ-EF1a-hTauP301L-EGFP and Adeno-GFAP-GFP viruses into the hippocampi of 5-month-old APP/PS1 mice.Three months post-injection,these mice exhibited pronounced astrogliosis,substantial amyloid-βplaque accumulation,extensiveneurofibrillarytangles,accelerated neuronal loss,elevated astrocytic GABA levels,and significant spatial memory deficits.Notably,these pathological features were less severe in AAVTauP301L-expressing APP/PS1 mice without augmented reactive astrogliosis.These findings indicate an exacerbating role of severe reactive astrogliosis in amyloid-βplaque and neurofibrillary tangle-associated pathology.The APP/PS1-TauP301L-Adeno mouse model provides a valuable tool for advancing therapeutic research aimed at mitigating the progression of AD.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Degree and Postgraduate Education Teaching Reform Project of Jiangxi Province(No.JXYJG-2020-026).
文摘AIM:To assess the possibility of using different large language models(LLMs)in ocular surface diseases by selecting five different LLMS to test their accuracy in answering specialized questions related to ocular surface diseases:ChatGPT-4,ChatGPT-3.5,Claude 2,PaLM2,and SenseNova.METHODS:A group of experienced ophthalmology professors were asked to develop a 100-question singlechoice question on ocular surface diseases designed to assess the performance of LLMs and human participants in answering ophthalmology specialty exam questions.The exam includes questions on the following topics:keratitis disease(20 questions),keratoconus,keratomalaciac,corneal dystrophy,corneal degeneration,erosive corneal ulcers,and corneal lesions associated with systemic diseases(20 questions),conjunctivitis disease(20 questions),trachoma,pterygoid and conjunctival tumor diseases(20 questions),and dry eye disease(20 questions).Then the total score of each LLMs and compared their mean score,mean correlation,variance,and confidence were calculated.RESULTS:GPT-4 exhibited the highest performance in terms of LLMs.Comparing the average scores of the LLMs group with the four human groups,chief physician,attending physician,regular trainee,and graduate student,it was found that except for ChatGPT-4,the total score of the rest of the LLMs is lower than that of the graduate student group,which had the lowest score in the human group.Both ChatGPT-4 and PaLM2 were more likely to give exact and correct answers,giving very little chance of an incorrect answer.ChatGPT-4 showed higher credibility when answering questions,with a success rate of 59%,but gave the wrong answer to the question 28% of the time.CONCLUSION:GPT-4 model exhibits excellent performance in both answer relevance and confidence.PaLM2 shows a positive correlation(up to 0.8)in terms of answer accuracy during the exam.In terms of answer confidence,PaLM2 is second only to GPT4 and surpasses Claude 2,SenseNova,and GPT-3.5.Despite the fact that ocular surface disease is a highly specialized discipline,GPT-4 still exhibits superior performance,suggesting that its potential and ability to be applied in this field is enormous,perhaps with the potential to be a valuable resource for medical students and clinicians in the future.
基金Supported by the China Health Promotion Foundation Young Doctors'Research Foundation for Inflammatory Bowel Disease,the Taishan Scholars Program of Shandong Province,China,No.tsqn202306343National Natural Science Foundation of China,No.82270578.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a global health burden that affects millions of individuals worldwide,necessitating extensive patient education.Large language models(LLMs)hold promise for addressing patient information needs.However,LLM use to deliver accurate and comprehensible IBD-related medical information has yet to be thoroughly investigated.AIM To assess the utility of three LLMs(ChatGPT-4.0,Claude-3-Opus,and Gemini-1.5-Pro)as a reference point for patients with IBD.METHODS In this comparative study,two gastroenterology experts generated 15 IBD-related questions that reflected common patient concerns.These questions were used to evaluate the performance of the three LLMs.The answers provided by each model were independently assessed by three IBD-related medical experts using a Likert scale focusing on accuracy,comprehensibility,and correlation.Simultaneously,three patients were invited to evaluate the comprehensibility of their answers.Finally,a readability assessment was performed.RESULTS Overall,each of the LLMs achieved satisfactory levels of accuracy,comprehensibility,and completeness when answering IBD-related questions,although their performance varies.All of the investigated models demonstrated strengths in providing basic disease information such as IBD definition as well as its common symptoms and diagnostic methods.Nevertheless,when dealing with more complex medical advice,such as medication side effects,dietary adjustments,and complication risks,the quality of answers was inconsistent between the LLMs.Notably,Claude-3-Opus generated answers with better readability than the other two models.CONCLUSION LLMs have the potential as educational tools for patients with IBD;however,there are discrepancies between the models.Further optimization and the development of specialized models are necessary to ensure the accuracy and safety of the information provided.
基金Supported by Government Assignment,No.1023022600020-6RSF Grant,No.24-15-00549Ministry of Science and Higher Education of the Russian Federation within the Framework of State Support for the Creation and Development of World-Class Research Center,No.075-15-2022-304.
文摘BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.
基金National Key Research and Development Program,Grant/Award Number:2022YFD1800505Hainan Province Science and Technology Special Fund,Grant/Award Number:ZDYF2024XDNY198+1 种基金Beijing Municipal Natural Science Foundation,Grant/Award Number:6232025Natural Science Foundation of China,Grant/Award Number:32272960。
文摘Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
基金supported by the National Key R&D Program of China(2023YFC3603800,2023YFC3603801)National Natural Science Foundation of China(82202793,82172534,82372574)+3 种基金Natural Science Foundation of Sichuan Province(2023NSFSC1999,2023NSFSC1495)Young and Middle-Aged Leading Talent Cultivation Project of Sichuan University(JH20231160)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0526000)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC21038)。
文摘Ischemic heart disease(IHD)remains a leading contributor to cardiovascular disease(CVD)worldwide.Despite advances in diagnostic and therapeutic approaches,translational research demands robust large animal models to bridge the gap between experimental interventions and clinical application.Among these,porcine models have gained prominence due to their anatomical,physiological,immunological,and genomic similarities to humans.This review provides a comprehensive overview of current methodologies for establishing porcine IHD models,critically assesses emerging rehabilitative strategies,and outlines innovative therapeutic technologies,with the goal of guiding model selection and fostering the development of novel treatment strategies.
文摘BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.
基金supported by the National Natural Science Foundation of China(32430083).
文摘The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.
基金supported by the National Natural Science Foundation of China(No.32371475)the Natural Science Foundation of Jiangsu Province,Major Project(No.BK20222008).
文摘Multiorgan-on-a-chip(MOoC)systems are advanced microfluidic devices that integrate multiple organ models into a single modular unit,each composed of cells derived from various tissues or organs.These systems enable interorgan communication and accurately replicate physiological conditions,providing a more physiologically relevant modeling framework for constructing disease models and predicting drug efficacy and toxicity.MOoC systems also provide significant advantages in terms of flexibility,cost-effectiveness,and reproducibility,making them valuable tools for drug development and toxicity assessment.In this review,we first provide an overview of the MOoC technology,covering cell sources,stimulations,materials and fabrication techniques,and biosensors.We then examine the application of MOoC systems in disease modeling,focusing on cancer metastasis,metabolic disorders,and cardiovascular disease.We next discuss the use of MOoC systems in drug toxicity evaluation and drug screening,emphasizing their role in providing comprehensive assessments of drug effects.Finally,we address the challenges it faces and the future perspectives of the MOoC technology.
基金Handan City Science and Technology Research and Development Program Project Application(Project No.:23422083096ZC)。
文摘Objective:To analyze the impact and mechanism of the SOC model intervention on improving health literacy and reducing disease uncertainty among young and middle-aged patients with coronary heart disease.Methods:A hundred young and middle-aged patients with coronary heart disease from our hospital between March and October 2024 were randomly divided into an observation group and a control group,with 50 patients in each group.Both groups received routine nursing intervention,while the observation group also received intervention based on the Stages of Change(SOC)model.The intervention period was 30 days.Changes in self-efficacy,health literacy,and disease uncertainty were compared between the two groups before and after the intervention.Results:After the intervention,the self-efficacy scores of both groups increased significantly,and the observation group had higher self-efficacy scores than the control group,with a significant difference(P<0.05).Additionally,the observation group showed significantly higher levels of health literacy than the control group(P<0.001).Furthermore,the observation group had significantly lower scores for disease uncertainty compared to the control group(P<0.001).Conclusion:The SOC model,in addition to routine nursing,significantly affects self-efficacy,disease uncertainty,and health literacy among young and middle-aged patients with coronary heart disease.It helps to enhance patients’knowledge of coronary heart disease,improve health literacy levels,and reduce disease uncertainty,making it worthy of clinical promotion and application.
基金Supported by National Natural Science Foundation of China(No.82160195)Science and Technology Project of Jiangxi Provincial Department of Education(No.GJJ200169)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2020A0087)Science and Technology Project of Jiangxi Health Commission(No.202130210).
文摘AIM:To assess the performance of five distinct large language models(LLMs;ChatGPT-3.5,ChatGPT-4,PaLM2,Claude 2,and SenseNova)in comparison to two human cohorts(a group of funduscopic disease experts and a group of ophthalmologists)on the specialized subject of funduscopic disease.METHODS:Five distinct LLMs and two distinct human groups independently completed a 100-item funduscopic disease test.The performance of these entities was assessed by comparing their average scores,response stability,and answer confidence,thereby establishing a basis for evaluation.RESULTS:Among all the LLMs,ChatGPT-4 and PaLM2 exhibited the most substantial average correlation.Additionally,ChatGPT-4 achieved the highest average score and demonstrated the utmost confidence during the exam.In comparison to human cohorts,ChatGPT-4 exhibited comparable performance to ophthalmologists,albeit falling short of the expertise demonstrated by funduscopic disease specialists.CONCLUSION:The study provides evidence of the exceptional performance of ChatGPT-4 in the domain of funduscopic disease.With continued enhancements,validated LLMs have the potential to yield unforeseen advantages in enhancing healthcare for both patients and physicians.
文摘BACKGROUND At present,there is a lack of non-invasive indicators to evaluate the changes in endoscopic activity between two visits for patients with Crohn's disease(CD).AIM To develop a model for predicting whether endoscopic activity will improve in CD patients.METHODS This is a single-center retrospective study that included patients diagnosed with CD from January 2014 to December 2022.The patients were randomly divided into a modeling group(70%)and an internal validation group(30%),with an external validation group from January 2023 to March 2024.Univariate and binary logistic regression analyses were conducted to identify independent risk factors,which were used to construct a nomogram model.The model's performance was evaluated using receiver operating characteristic curves,calibration curves,and decision curve analysis(DCA).Additionally,further sensitivity analyses were performed.RESULTS One hundred seventy patients were included in the training group,while 64 were included in the external validation group.A binary logistic stepwise regression analysis revealed that the changes in the amplitudes of albumin(ALB)and fibrinogen(FIB)were independent risk factors for endoscopic improvement.A nomogram model was developed based on these risk factors.The area under the curve of the model for the training group,internal validation group,and external validation group were 0.802,0.788,and 0.787,respectively.The average absolute errors of the calibration curves were 0.011,0.016,and 0.018,respectively.DCA indicated that the model performs well in clinical practice.Additionally,sensitivity analysis demonstrated that the model has strong robustness and applicability.CONCLUSION Our study shows that changes in the amplitudes of ALB and FIB are effective predictors of endoscopic improvement in patients with CD during follow-up visits compared to their previous ones.
基金supported by Zhejiang Provincial Natural Science Foundation of China(Grant No.LR25D010003)The Zhejiang Provincial Key Research and Development Program(Grant No.2023C02018)National Natural Science Foundation of China(Grant No.42401400).
文摘The frequent outbreaks of crop diseases pose a serious threat to global agricultural production and food security.Data-driven forecasting models have emerged as an effective approach to support early warning and management,yet the lack of user-friendly tools for model development remains a major bottleneck.This study presents the Multi-Scenario Crop Disease Forecasting Modeling System(MSDFS),an open-source platform that enables end-to-end model construction-from multi-source data ingestion and feature engineering to training,evaluation,and deployment-across four representative scenarios:static point-based,static grid-based,dynamic point-based,and dynamic grid-based.Unlike conventional frameworks,MSDFS emphasizes modeling flexibility,allowing users to build,compare,and interpret diverse forecasting approaches within a unified workflow.A notable feature of the system is the integration of a weather scenario generator,which facilitates comprehensive testing of model performance and adaptability under extreme climatic conditions.Case studies corresponding to the four scenarios were used to validate the system,with overall accuracy(OA)ranging from 73%to 93%.By lowering technical barriers,the system is designed to serve plant protection managers and agricultural producers without advanced programming expertise,providing a practical modeling tool that supports the construction of smart plant protection systems.
基金Supported by China Health Promotion Foundation Young Doctors’Research Foundation for Inflammatory Bowel DiseaseTaishan Scholars Program of Shandong Province,China,NO.tsqn202306343National Natural Science Foundation of China,No.82270580,No.82070552,No.82270578,and No.82300599.
文摘BACKGROUND Gastrointestinal diseases have complex etiologies and clinical presentations.An accurate diagnosis requires physicians to integrate diverse information,including medical history,laboratory test results,and imaging findings.Existing artificial intelligence-assisted diagnostic tools are limited to single-modality information,resulting in recommendations that are often incomplete and may be associated with clinical or legal risks.AIM To develop and evaluate a collaborative multimodal large language model(LLM)framework for clinical decision-making in digestive diseases.METHODS In this observational study,DeepGut,a multimodal LLM collaborative diagnostic framework,was developed to integrate four distinct large models into a four-tiered structure.The framework sequentially accomplishes multimodal infor-mation extraction,logical“chain”construction,diagnostic and treatment suggestion generation,and risk analysis.The model was evaluated using objective metrics,which assess the reliability and comprehensiveness of model-generated results,and subjective expert opinions,which examine the effectiveness of the framework in assisting physicians.RESULTS The diagnostic and treatment recommendations generated by the DeepGut framework achieved exceptional performance,with a diagnostic accuracy of 97.8%,diagnostic completeness of 93.9%,treatment plan accuracy of 95.2%,and treatment plan completeness of 98.0%,significantly surpassing the capabilities of single-modal LLM-based diagnostic tools.Experts evaluating the framework commended the completeness,relevance,and logical coherence of its outputs.However,the collaborative multimodal LLM approach resulted in increased input and output token counts,leading to higher computational costs and extended diagnostic times.CONCLUSION The framework achieves successful integration of multimodal diagnostic data,demonstrating enhanced performance enabled by multimodal LLM collaboration,which opens new horizons for the clinical application of artificial intelligence-assisted technology.
