The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using d...Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using deep learning algorithms further enhances performance;nevertheless,it is challenging due to the nature of small-scale and imbalanced PD datasets.This paper proposed a convolutional neural network-based deep support vector machine(CNN-DSVM)to automate the feature extraction process using CNN and extend the conventional SVM to a DSVM for better classification performance in small-scale PD datasets.A customized kernel function reduces the impact of biased classification towards the majority class(healthy candidates in our consideration).An improved generative adversarial network(IGAN)was designed to generate additional training data to enhance the model’s performance.For performance evaluation,the proposed algorithm achieves a sensitivity of 97.6%and a specificity of 97.3%.The performance comparison is evaluated from five perspectives,including comparisons with different data generation algorithms,feature extraction techniques,kernel functions,and existing works.Results reveal the effectiveness of the IGAN algorithm,which improves the sensitivity and specificity by 4.05%–4.72%and 4.96%–5.86%,respectively;and the effectiveness of the CNN-DSVM algorithm,which improves the sensitivity by 1.24%–57.4%and specificity by 1.04%–163%and reduces biased detection towards the majority class.The ablation experiments confirm the effectiveness of individual components.Two future research directions have also been suggested.展开更多
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
基金The work described in this paper was fully supported by a grant from Hong Kong Metropolitan University(RIF/2021/05).
文摘Parkinson’s disease(PD)is a debilitating neurological disorder affecting over 10 million people worldwide.PD classification models using voice signals as input are common in the literature.It is believed that using deep learning algorithms further enhances performance;nevertheless,it is challenging due to the nature of small-scale and imbalanced PD datasets.This paper proposed a convolutional neural network-based deep support vector machine(CNN-DSVM)to automate the feature extraction process using CNN and extend the conventional SVM to a DSVM for better classification performance in small-scale PD datasets.A customized kernel function reduces the impact of biased classification towards the majority class(healthy candidates in our consideration).An improved generative adversarial network(IGAN)was designed to generate additional training data to enhance the model’s performance.For performance evaluation,the proposed algorithm achieves a sensitivity of 97.6%and a specificity of 97.3%.The performance comparison is evaluated from five perspectives,including comparisons with different data generation algorithms,feature extraction techniques,kernel functions,and existing works.Results reveal the effectiveness of the IGAN algorithm,which improves the sensitivity and specificity by 4.05%–4.72%and 4.96%–5.86%,respectively;and the effectiveness of the CNN-DSVM algorithm,which improves the sensitivity by 1.24%–57.4%and specificity by 1.04%–163%and reduces biased detection towards the majority class.The ablation experiments confirm the effectiveness of individual components.Two future research directions have also been suggested.
