Varying-coefficient models are a useful extension of classical linear model. They are widely applied to economics, biomedicine, epidemiology, and so on. There are extensive studies on them in the latest three decade y...Varying-coefficient models are a useful extension of classical linear model. They are widely applied to economics, biomedicine, epidemiology, and so on. There are extensive studies on them in the latest three decade years. In this paper, many of models related to varying-coefficient models are gathered up. All kinds of the estimation procedures and theory of hypothesis test on the varying-coefficients model are summarized. Prom my opinion, some aspects waiting to study are proposed.展开更多
In this paper, a model averaging method is proposed for varying-coefficient models with response missing at random by establishing a weight selection criterion based on cross-validation. Under certain regularity condi...In this paper, a model averaging method is proposed for varying-coefficient models with response missing at random by establishing a weight selection criterion based on cross-validation. Under certain regularity conditions, it is proved that the proposed method is asymptotically optimal in the sense of achieving the minimum squared error.展开更多
In this paper, we extend the generalized likelihood ratio test to the varying-coefficient models with censored data. We investigate the asymptotic behavior of the proposed test and demonstrate that its limiting null d...In this paper, we extend the generalized likelihood ratio test to the varying-coefficient models with censored data. We investigate the asymptotic behavior of the proposed test and demonstrate that its limiting null distribution follows a distribution, with the scale constant and the number of degree of freedom being independent of nuisance parameters or functions, which is called the wilks phenomenon. Both simulated and real data examples are given to illustrate the performance of the testing approach.展开更多
Climate model prediction has been improved by enhancing model resolution as well as the implementation of sophisticated physical parameterization and refinement of data assimilation systems[section 6.1 in Wang et al.(...Climate model prediction has been improved by enhancing model resolution as well as the implementation of sophisticated physical parameterization and refinement of data assimilation systems[section 6.1 in Wang et al.(2025)].In relation to seasonal forecasting and climate projection in the East Asian summer monsoon season,proper simulation of the seasonal migration of rain bands by models is a challenging and limiting factor[section 7.1 in Wang et al.(2025)].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
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
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:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual pat...Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.展开更多
A partially varying-coefficient model is one of the useful modelling tools.In this model, some coefficients of a linear model are kept to be constant whilst the others areallowed to vary with another factor. However, ...A partially varying-coefficient model is one of the useful modelling tools.In this model, some coefficients of a linear model are kept to be constant whilst the others areallowed to vary with another factor. However, rarely can the analysts know a priori whichcoefficients can be assumed to be constant and which ones are varying with the given factor.Therefore, the identification problem of the constant coefficients should be solved before thepartially varying-coefficient model is used to analyze a real-world data set. In this article, asimple test method is proposed to achieve this task, in which the test statistic is constructed asthe sample variance of the estimates of each coefficient function in a well-knownvarying-coefficient model. Moreover two procedures, called F-approximation and three-moment χ~2approximation, are employed to derive the p-value of the test. Furthermore, some simulations areconducted to examine the performance of the test and the results are satisfactory.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Varying-coefficient single-index model( VCSIM) avoids the so-called "curse of dimensionality " and is flexible enough to include several important statistical models. This paper considers statistical diagnos...Varying-coefficient single-index model( VCSIM) avoids the so-called "curse of dimensionality " and is flexible enough to include several important statistical models. This paper considers statistical diagnosis for VCSIM. First,the parametric estimation equation is established based on empirical likelihood. Then,some diagnosis statistics are defined. At last, an example is given to illustrate all the results.展开更多
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
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
This article is concerned with the estimating problem of semiparametric varyingcoefficient partially linear regression models. By combining the local polynomial and least squares procedures Fan and Huang （2005） prop...This article is concerned with the estimating problem of semiparametric varyingcoefficient partially linear regression models. By combining the local polynomial and least squares procedures Fan and Huang （2005） proposed a profile least squares estimator for the parametric component and established its asymptotic normality. We further show that the profile least squares estimator can achieve the law of iterated logarithm. Moreover, we study the estimators of the functions characterizing the non-linear part as well as the error variance. The strong convergence rate and the law of iterated logarithm are derived for them, respectively.展开更多
When a real-world data set is fitted to a specific type of models,it is often encountered that one or a set of observations have undue influence on the model fitting,which may lead to misleading conclusions.Therefore,...When a real-world data set is fitted to a specific type of models,it is often encountered that one or a set of observations have undue influence on the model fitting,which may lead to misleading conclusions.Therefore,it is necessary for data analysts to identify these influential observations and assess their impact on various aspects of model fitting.In this paper,one type of modified Cook's distances is defined to gauge the influence of one or a set observations on the estimate of the constant coefficient part in partially varying-coefficient models,and the Cook's distances are expressed as functions of the corresponding residuals and leverages.Meanwhile,a bootstrap procedure is suggested to derive the reference values for the proposed Cook's distances.Some simulations are conducted,and a real-world data set is further analyzed to examine the performance of the proposed method.The experimental results are satisfactory.展开更多
Consider the semiparametric varying-coefficient heteroscedastic partially linear model Yi = X^T i β＋ Z^T iα（Ti） ＋ σiei, 1 ≤ i≤ n, where σ ^2i= f（Ui）, β is a p × 1 column vector of unknown parameter, ...Consider the semiparametric varying-coefficient heteroscedastic partially linear model Yi = X^T i β＋ Z^T iα（Ti） ＋ σiei, 1 ≤ i≤ n, where σ ^2i= f（Ui）, β is a p × 1 column vector of unknown parameter, （Xi, Zi, Ti, Ui） are random design q-dimensional vector of unknown functions, el points, Yi are the response variables, α（-） is a are random errors. For both cases that f（.） is known and unknown, we propose the empirical log-likelihood ratio statistics for the parameter f（.）. For each case, a nonparametric version of Wilks＇ theorem is derived. The results are then used to construct confidence regions of the parameter. Simulation studies are carried out to assess the performance of the empirical likelihood method.展开更多
In this paper,we present a variable selection procedure by combining basis function approximations with penalized estimating equations for varying-coefficient models with missing response at random.With appropriate se...In this paper,we present a variable selection procedure by combining basis function approximations with penalized estimating equations for varying-coefficient models with missing response at random.With appropriate selection of the tuning parameters,we establish the consistency of the variable selection procedure and the optimal convergence rate of the regularized estimators.A simulation study is undertaken to assess the finite sample performance of the proposed variable selection procedure.展开更多
This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble lear...This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and AB-RBFN.Additionally,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and validation.The models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to roads.These factors were instrumental in predicting the output variable,which was the probability of landslide occurrence.Statistical analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other models.The AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of 0.926.These results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.展开更多
Conducting predictability studies is essential for tracing the source of forecast errors,which not only leads to the improvement of observation and forecasting systems,but also enhances the understanding of weather an...Conducting predictability studies is essential for tracing the source of forecast errors,which not only leads to the improvement of observation and forecasting systems,but also enhances the understanding of weather and climate phenomena.In the past few decades,dynamical numerical models have been the primary tools for predictability studies,achieving significant progress.Nowadays,with the advances in artificial intelligence(AI)techniques and accumulations of vast meteorological data,modeling weather and climate events using modern data-driven approaches is becoming trendy,where FourCastNet,Pangu-Weather,and GraphCast are successful pioneers.In this perspective article,we suggest AI models should not be limited to forecasting but be expanded to predictability studies,leveraging AI's advantages of high efficiency and self-contained optimization modules.To this end,we first remark that AI models should possess high simulation capability with fine spatiotemporal resolution for two kinds of predictability studies.AI models with high simulation capabilities comparable to numerical models can be considered to provide solutions to partial differential equations in a data-driven way.Then,we highlight several specific predictability issues with well-determined nonlinear optimization formulizations,which can be well-studied using AI models,holding significant scientific value.In addition,we advocate for the incorporation of AI models into the synergistic cycle of the cognition–observation–model paradigm.Comprehensive predictability studies have the potential to transform“big data”to“big and better data”and shift the focus from“AI for forecasts”to“AI for science”,ultimately advancing the development of the atmospheric and oceanic sciences.展开更多
Large language models(LLMs)have significantly advanced artificial intelligence(AI)by excelling in tasks such as understanding,generation,and reasoning across multiple modalities.Despite these achievements,LLMs have in...Large language models(LLMs)have significantly advanced artificial intelligence(AI)by excelling in tasks such as understanding,generation,and reasoning across multiple modalities.Despite these achievements,LLMs have inherent limitations including outdated information,hallucinations,inefficiency,lack of interpretability,and challenges in domain-specific accuracy.To address these issues,this survey explores three promising directions in the post-LLM era:knowledge empowerment,model collaboration,and model co-evolution.First,we examine methods of integrating external knowledge into LLMs to enhance factual accuracy,reasoning capabilities,and interpretability,including incorporating knowledge into training objectives,instruction tuning,retrieval-augmented inference,and knowledge prompting.Second,we discuss model collaboration strategies that leverage the complementary strengths of LLMs and smaller models to improve efficiency and domain-specific performance through techniques such as model merging,functional model collaboration,and knowledge injection.Third,we delve into model co-evolution,in which multiple models collaboratively evolve by sharing knowledge,parameters,and learning strategies to adapt to dynamic environments and tasks,thereby enhancing their adaptability and continual learning.We illustrate how the integration of these techniques advances AI capabilities in science,engineering,and society—particularly in hypothesis development,problem formulation,problem-solving,and interpretability across various domains.We conclude by outlining future pathways for further advancement and applications.展开更多
基金Foundation item： Supported by the National Natural Science Foundation of China（10501053） Acknowledgement I would like to thank Henan Society of Applied Statistics for which give me a chance to declare my opinion about the varying-coefficient model.
文摘Varying-coefficient models are a useful extension of classical linear model. They are widely applied to economics, biomedicine, epidemiology, and so on. There are extensive studies on them in the latest three decade years. In this paper, many of models related to varying-coefficient models are gathered up. All kinds of the estimation procedures and theory of hypothesis test on the varying-coefficients model are summarized. Prom my opinion, some aspects waiting to study are proposed.
文摘In this paper, a model averaging method is proposed for varying-coefficient models with response missing at random by establishing a weight selection criterion based on cross-validation. Under certain regularity conditions, it is proved that the proposed method is asymptotically optimal in the sense of achieving the minimum squared error.
文摘In this paper, we extend the generalized likelihood ratio test to the varying-coefficient models with censored data. We investigate the asymptotic behavior of the proposed test and demonstrate that its limiting null distribution follows a distribution, with the scale constant and the number of degree of freedom being independent of nuisance parameters or functions, which is called the wilks phenomenon. Both simulated and real data examples are given to illustrate the performance of the testing approach.
文摘Climate model prediction has been improved by enhancing model resolution as well as the implementation of sophisticated physical parameterization and refinement of data assimilation systems[section 6.1 in Wang et al.(2025)].In relation to seasonal forecasting and climate projection in the East Asian summer monsoon season,proper simulation of the seasonal migration of rain bands by models is a challenging and limiting factor[section 7.1 in Wang et al.(2025)].
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.
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 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.
基金supported by the Natural Science Foundation of Guangdong Province(No.2021B1515120053)Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515140166).
文摘Background:Therapeutic responses of breast cancer vary among patients and lead to drug resistance and recurrence due to the heterogeneity.Current preclinical models,however,are inadequate for predicting individual patient responses towards different drugs.This study aimed to investigate the patient-derived breast cancer culture models for drug sensitivity evaluations.Methods:Tumor and adjacent tissues from female breast cancer patients were collected during surgery.Patient-derived breast cancer cells were cultured using the conditional reprogramming technique to establish 2D models.The obtained patient-derived conditional reprogramming breast cancer(CRBC)cells were subsequently embedded in alginate-gelatin methacryloyl hydrogel microspheres to form 3D culture models.Comparisons between 2D and 3D models were made using immunohistochemistry(tumor markers),MTS assays(cell viability),flow cytometry(apoptosis),transwell assays(migration),and Western blotting(protein expression).Drug sensitivity tests were conducted to evaluate patient-specific responses to anti-cancer agents.Results:2D and 3D culture models were successfully established using samples from eight patients.The 3D models retained histological and marker characteristics of the original tumors.Compared to 2D cultures,3D models exhibited increased apoptosis,enhanced drug resistance,elevated stem cell marker expression,and greater migration ability—features more reflective of in vivo tumor behavior.Conclusion:Patient-derived 3D CRBC models effectively mimic the in vivo tumor microenvironment and demonstrate stronger resistance to anti-cancer drugs than 2D models.These hydrogel-based models offer a cost-effective and clinically relevant platform for drug screening and personalized breast cancer treatment.
文摘A partially varying-coefficient model is one of the useful modelling tools.In this model, some coefficients of a linear model are kept to be constant whilst the others areallowed to vary with another factor. However, rarely can the analysts know a priori whichcoefficients can be assumed to be constant and which ones are varying with the given factor.Therefore, the identification problem of the constant coefficients should be solved before thepartially varying-coefficient model is used to analyze a real-world data set. In this article, asimple test method is proposed to achieve this task, in which the test statistic is constructed asthe sample variance of the estimates of each coefficient function in a well-knownvarying-coefficient model. Moreover two procedures, called F-approximation and three-moment χ~2approximation, are employed to derive the p-value of the test. Furthermore, some simulations areconducted to examine the performance of the test and the results are satisfactory.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
文摘Varying-coefficient single-index model( VCSIM) avoids the so-called "curse of dimensionality " and is flexible enough to include several important statistical models. This paper considers statistical diagnosis for VCSIM. First,the parametric estimation equation is established based on empirical likelihood. Then,some diagnosis statistics are defined. At last, an example is given to illustrate all the results.
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
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 Natural Science Funds for Distinguished Young Scholar (70825004)National Natural Science Foundation of China (NSFC) (10731010 and 10628104)+3 种基金the National Basic Research Program (2007CB814902)Creative Research Groups of China (10721101)Leading Academic Discipline Program, the 10th five year plan of 211 Project for Shanghai University of Finance and Economics211 Project for Shanghai University of Financeand Economics (the 3rd phase)
文摘This article is concerned with the estimating problem of semiparametric varyingcoefficient partially linear regression models. By combining the local polynomial and least squares procedures Fan and Huang （2005） proposed a profile least squares estimator for the parametric component and established its asymptotic normality. We further show that the profile least squares estimator can achieve the law of iterated logarithm. Moreover, we study the estimators of the functions characterizing the non-linear part as well as the error variance. The strong convergence rate and the law of iterated logarithm are derived for them, respectively.
基金the National Natural Science Foundations of China(No.10531030,No.60675013)
文摘When a real-world data set is fitted to a specific type of models,it is often encountered that one or a set of observations have undue influence on the model fitting,which may lead to misleading conclusions.Therefore,it is necessary for data analysts to identify these influential observations and assess their impact on various aspects of model fitting.In this paper,one type of modified Cook's distances is defined to gauge the influence of one or a set observations on the estimate of the constant coefficient part in partially varying-coefficient models,and the Cook's distances are expressed as functions of the corresponding residuals and leverages.Meanwhile,a bootstrap procedure is suggested to derive the reference values for the proposed Cook's distances.Some simulations are conducted,and a real-world data set is further analyzed to examine the performance of the proposed method.The experimental results are satisfactory.
基金Supported by the National Natural Science Foundation of China (Grant No. 71171003)Natural Science Research Project of Anhui Provincial Colleges (Grant No. KJ2011A032)+3 种基金Anhui Polytechnic University Foundation for Recruiting Talent (Grant Nos. 2011YQQ0042009YQQ005)Young Teachers Science Research Foundation of Anhui Polytechnic University (Grant No. 2009YQ035)Anhui Provincial Natural Science Foundation
文摘Consider the semiparametric varying-coefficient heteroscedastic partially linear model Yi = X^T i β＋ Z^T iα（Ti） ＋ σiei, 1 ≤ i≤ n, where σ ^2i= f（Ui）, β is a p × 1 column vector of unknown parameter, （Xi, Zi, Ti, Ui） are random design q-dimensional vector of unknown functions, el points, Yi are the response variables, α（-） is a are random errors. For both cases that f（.） is known and unknown, we propose the empirical log-likelihood ratio statistics for the parameter f（.）. For each case, a nonparametric version of Wilks＇ theorem is derived. The results are then used to construct confidence regions of the parameter. Simulation studies are carried out to assess the performance of the empirical likelihood method.
基金Supported by the National Natural Science Foundation of China (Grant No. 10871013)the Natural Science Foundation of Beijing (Grant No. 1072004), the Natural Science Foundation of Guangxi (Grant No. 2010GXNSFB013051)the Graduate Student Foundation of Hechi University (Grant No. 2008QS-N014)
文摘In this paper,we present a variable selection procedure by combining basis function approximations with penalized estimating equations for varying-coefficient models with missing response at random.With appropriate selection of the tuning parameters,we establish the consistency of the variable selection procedure and the optimal convergence rate of the regularized estimators.A simulation study is undertaken to assess the finite sample performance of the proposed variable selection procedure.
基金the University of Transport Technology under the project entitled“Application of Machine Learning Algorithms in Landslide Susceptibility Mapping in Mountainous Areas”with grant number DTTD2022-16.
文摘This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and AB-RBFN.Additionally,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and validation.The models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to roads.These factors were instrumental in predicting the output variable,which was the probability of landslide occurrence.Statistical analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other models.The AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of 0.926.These results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.
基金in part supported by the National Natural Science Foundation of China(Grant Nos.42288101,42405147 and 42475054)in part by the China National Postdoctoral Program for Innovative Talents(Grant No.BX20230071)。
文摘Conducting predictability studies is essential for tracing the source of forecast errors,which not only leads to the improvement of observation and forecasting systems,but also enhances the understanding of weather and climate phenomena.In the past few decades,dynamical numerical models have been the primary tools for predictability studies,achieving significant progress.Nowadays,with the advances in artificial intelligence(AI)techniques and accumulations of vast meteorological data,modeling weather and climate events using modern data-driven approaches is becoming trendy,where FourCastNet,Pangu-Weather,and GraphCast are successful pioneers.In this perspective article,we suggest AI models should not be limited to forecasting but be expanded to predictability studies,leveraging AI's advantages of high efficiency and self-contained optimization modules.To this end,we first remark that AI models should possess high simulation capability with fine spatiotemporal resolution for two kinds of predictability studies.AI models with high simulation capabilities comparable to numerical models can be considered to provide solutions to partial differential equations in a data-driven way.Then,we highlight several specific predictability issues with well-determined nonlinear optimization formulizations,which can be well-studied using AI models,holding significant scientific value.In addition,we advocate for the incorporation of AI models into the synergistic cycle of the cognition–observation–model paradigm.Comprehensive predictability studies have the potential to transform“big data”to“big and better data”and shift the focus from“AI for forecasts”to“AI for science”,ultimately advancing the development of the atmospheric and oceanic sciences.
基金supported in part by National Natural Science Foundation of China(62441605)。
文摘Large language models(LLMs)have significantly advanced artificial intelligence(AI)by excelling in tasks such as understanding,generation,and reasoning across multiple modalities.Despite these achievements,LLMs have inherent limitations including outdated information,hallucinations,inefficiency,lack of interpretability,and challenges in domain-specific accuracy.To address these issues,this survey explores three promising directions in the post-LLM era:knowledge empowerment,model collaboration,and model co-evolution.First,we examine methods of integrating external knowledge into LLMs to enhance factual accuracy,reasoning capabilities,and interpretability,including incorporating knowledge into training objectives,instruction tuning,retrieval-augmented inference,and knowledge prompting.Second,we discuss model collaboration strategies that leverage the complementary strengths of LLMs and smaller models to improve efficiency and domain-specific performance through techniques such as model merging,functional model collaboration,and knowledge injection.Third,we delve into model co-evolution,in which multiple models collaboratively evolve by sharing knowledge,parameters,and learning strategies to adapt to dynamic environments and tasks,thereby enhancing their adaptability and continual learning.We illustrate how the integration of these techniques advances AI capabilities in science,engineering,and society—particularly in hypothesis development,problem formulation,problem-solving,and interpretability across various domains.We conclude by outlining future pathways for further advancement and applications.
