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1.
J Toxicol Sci ; 49(5): 231-240, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692910

RESUMO

Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.


Assuntos
4-Aminopiridina , Frequência Cardíaca , Aprendizado de Máquina , Convulsões , Animais , Masculino , Convulsões/induzido quimicamente , Frequência Cardíaca/efeitos dos fármacos , 4-Aminopiridina/efeitos adversos , Ácido Caínico/toxicidade , Convulsivantes/toxicidade , Ranolazina , Bupropiona/toxicidade , Bupropiona/efeitos adversos , Eletrocardiografia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiopatologia , Telemetria , Biomarcadores
2.
Int J Pharm X ; 7: 100242, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38601059

RESUMO

In continuous pharmaceutical manufacturing processes, it is crucial to control the powder flow rate. The feeding process is characterized by the amount of powder delivered per screw rotation, referred to as the feed factor. This study aims to develop models for predicting the feed factor profiles (FFPs) of two-component mixed powders with various formulations, while most previous studies have focused on single-component powders. It further aims to identify the suitable model type and to determine the significance of material properties in enhancing prediction accuracy by using several FFP prediction models with different input variables. Four datasets from the experiment were generated with different ranges of the mass fraction of active pharmaceutical ingredients (API) and the powder weight in the hopper. The candidates for the model inputs are (a) the mass fraction of API, (b) process parameters, and (c) material properties. It is desirable to construct a high-performance prediction model without the material properties because their measurement is laborious. The results show that using (c) as input variables did not improve the prediction accuracy as much, thus there is no need to use them.

3.
Sci Rep ; 13(1): 11534, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460599

RESUMO

Mathematical formulas play a prominent role in science, technology, engineering, and mathematics (STEM) documents; understanding STEM documents usually requires knowing the difference between equation groups containing multiple equations. When two equation groups can be transformed into the same form, we call the equation groups equivalent. Existing tools cannot judge the equivalence of two equation groups; thus, we develop an algorithm to judge such an equivalence using a computer algebra system. The proposed algorithm first eliminates variables appearing only in either equation group. It then checks the equivalence of the equations one by one: the equations with identical algebraic solutions for the same variable are judged equivalent. If each equation in one equation group is equivalent to an equation in the other, the equation groups are judged equivalent; otherwise, non-equivalent. We generated 50 pairs of equation groups for evaluation. The proposed method accurately judged the equivalence of all pairs. This method is expected to facilitate comprehension of a large amount of mathematical information in STEM documents. Furthermore, this is a necessary step for machines to understand equations, including process models.

4.
Int J Pharm ; 642: 123178, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37364782

RESUMO

Implementation of the design space (DS) is a scientific concept for ensuring quality to be submitted as a part of the regulatory filing of a drug product for approval to market. An empirical approach is constructing the DS based on the regression model whose inputs are process parameters and material attributes over the different unit operations, i.e., a high-dimensional statistical model. While the high-dimensional model assures quality and process flexibility through a comprehensive process understanding, it has difficulty visualizing the feasible range of input parameters, i.e., DS. Therefore, this study proposes a greedy approach to constructing the extensive and flexible low-dimensional DS based on the high-dimensional statistical model and the observed internal representations that satisfies both comprehensive process understanding and the DS visualization capability. Introducing the observed correlation structure enabled the dimensionality reduction of the DS. The non-critical controllable parameters were fixed to the target values in visualizing the low-dimensional DS as a function of critical parameters. The expected variation of non-critical non-controllable parameters was considered the source of variation in prediction. The case study demonstrated the proposed approach's usefulness for developing the pharmaceutical manufacturing process.


Assuntos
Desenvolvimento de Medicamentos , Modelos Estatísticos , Tecnologia Farmacêutica/métodos
5.
Artif Intell Med ; 128: 102310, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35534147

RESUMO

Although medical checkup data would be useful for identifying unknown factors of disease progression, a causal relationship between checkup items should be taken into account for precise analysis. Missing values in medical checkup data must be appropriately imputed because checkup items vary from person to person, and items that have not been tested include missing values. In addition, the patients with target diseases or disorders are small in comparison with the total number of persons recorded in the data, which means medical checkup data is an imbalanced data analysis. We propose a new method for analyzing the causal relationship in medical checkup data to discover disease progression factors based on a linear non-Gaussian acyclic model (LiNGAM), a machine learning technique for causal inference. In the proposed method, specific regression coefficients calculated through LiNGAM were compared to estimate the causal strength of the checkup items on disease progression, which is referred to as LiNGAM-beta. We also propose an analysis framework consisting of LiNGAM-beta, collaborative filtering (CF), and a sampling approach for causal inference of medical checkup data. CF and the sampling approach are useful for missing value imputation and balancing of the data distribution. We applied the proposed analysis framework to medical checkup data for identifying factors of Nonalcoholic fatty liver disease (NAFLD) development. The checkup items related to metabolic syndrome and age showed high causal effects on NAFLD severity. The level of blood urea nitrogen (BUN) would have a negative effect on NAFLD severity. Snoring frequency, which is associated with obstructive sleep apnea, affected NAFLD severity, particularly in the male group. Sleep duration also affected NAFLD severity in persons over fifty years old. These analysis results are consistent with previous reports about the causes of NAFLD; for example, NAFLD and metabolic syndrome are mutual and bi-directionally related, and BUN has a negative effect on NAFLD progression. Thus, our analysis result is plausible. The proposed analysis framework including LiNGAM-beta can be applied to various medical checkup data and will contribute to discovering unknown disease factors.


Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Análise de Dados , Progressão da Doença , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Distribuição Normal
6.
Clin Neurophysiol ; 139: 80-89, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35569296

RESUMO

OBJECTIVE: Easily detecting patients with undiagnosed sleep apnea syndrome (SAS) requires a home-use SAS screening system. In this study, we validate a previously developed SAS screening methodology using a large clinical polysomnography (PSG) dataset (N = 938). METHODS: We combined R-R interval (RRI) and long short-term memory (LSTM), a type of recurrent neural networks, and created a model to discriminate respiratory conditions using the training dataset (N = 468). Its performance was validated using the validation dataset (N = 470). RESULTS: Our method screened patients with severe SAS (apnea hypopnea index; AHI ≥ 30) with an area under the curve (AUC) of 0.92, a sensitivity of 0.80, and a specificity of 0.84. In addition, the model screened patients with moderate/severe SAS (AHI ≥ 15) with an AUC of 0.89, a sensitivity of 0.75, and a specificity of 0.87. CONCLUSIONS: Our method achieved high screening performance when applied to a large clinical dataset. SIGNIFICANCE: Our method can help realize an easy-to-use SAS screening system because RRI data can be easily measured with a wearable heart rate sensor. It has been validated on a large dataset including subjects with various backgrounds and is expected to perform well in real-world clinical practice.


Assuntos
Síndromes da Apneia do Sono , Área Sob a Curva , Humanos , Programas de Rastreamento , Redes Neurais de Computação , Polissonografia , Síndromes da Apneia do Sono/diagnóstico
7.
Chem Pharm Bull (Tokyo) ; 70(1): 74-81, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34980737

RESUMO

Soft sensors are powerful tools for the implementation of process analytical technology (PAT). They are categorized into white-box (first-principle), black-box (statistical), and gray-box models. Gray-box models integrate white-box and black-box models to address each drawback, i.e., prediction accuracy and intuitiveness. Although they have been applied to various industrial processes, their applicability to water content monitoring in fluidized bed granulation has not been reported. In this study, we evaluated three types of gray-box models, i.e., parallel, serial, and combined gray-box models, in terms of prediction accuracy using real operating data on a commercial scale with two formulations. The gray-box models were constructed by integrating the heat and mass balance model (white-box model) and locally weighted partial least squares regression (LW-PLSR) model (black-box model). LW-PLSR was utilized to cope with collinearity and nonlinearity. In the serial gray-box models, LW-PLSR models adjusted the fitting parameters of the white-box model depending on the process parameters for each query. In the parallel gray-box or combined gray-box models, LW-PLSR models compensated for the output error of the white-box or serial gray-box models, respectively. The results demonstrated that all three types of gray-box models improved the prediction accuracy of the white-box models regardless of the formulation. Besides, we proposed the assessment method based on Hotelling's T2 and Q residual for gray-box models using LW-PLSR, which contributes decision support to select gray-box or white-box model. The accurate and descriptive gray-box models are expected to enhance process understanding and precise quality control in fluidized bed granulation.


Assuntos
Tecnologia Farmacêutica , Água/análise , Tamanho da Partícula
8.
Membranes (Basel) ; 11(10)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34677531

RESUMO

In petroleum refineries, naphtha reforming units produce reformate streams and as a by-product, hydrogen (H2). Naphtha reforming units traditionally deployed are designed as packed bed reactors (PBR). However, they are restrained by a high-pressure drop, diffusion limitations in the catalyst, and radial and axial gradients of temperature and concentration. A new design using the fluidized bed reactor (FBR) surpasses the issues of the PBR, whereby the incorporation of the membrane can improve the yield of products by selectively removing hydrogen from the reaction side. In this work, a sequential modular simulation (SMS) approach is adopted to simulate the hydrodynamics of a fluidized bed membrane reactor (FBMR) for catalytic reforming of naphtha in Aspen Plus. The reformer reactor is divided into five sections of plug flow reactors and a continuous stirrer tank reactor with the membrane module to simulate the overall FBMR. Similarly, a fluidized bed reactor (FBR), without membrane permeation phenomenon, is also modelled in the Aspen Plus environment for a comparative study with FBMR. In FBMR, the continuous elimination of permeated hydrogen enhanced the production of aromatics compound in the reformate stream. Moreover, the exergy and economic analyses were carried out for both FBR and FBMR.

9.
Sensors (Basel) ; 21(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067051

RESUMO

Heart rate variability, which is the fluctuation of the R-R interval (RRI) in electrocardiograms (ECG), has been widely adopted for autonomous evaluation. Since the HRV features that are extracted from RRI data easily fluctuate when arrhythmia occurs, RRI data with arrhythmia need to be modified appropriately before HRV analysis. In this study, we consider two types of extrasystoles-premature ventricular contraction (PVC) and premature atrial contraction (PAC)-which are types of extrasystoles that occur every day, even in healthy persons who have no cardiovascular diseases. A unified framework for ectopic RRI detection and a modification algorithm that utilizes an autoencoder (AE) type of neural network is proposed. The proposed framework consists of extrasystole occurrence detection from the RRI data and modification, whose targets are PVC and PAC. The RRI data are monitored by means of the AE in real time in the detection phase, and a denoising autoencoder (DAE) modifies the ectopic RRI caused by the detected extrasystole. These are referred to as AE-based extrasystole detection (AED) and DAE-based extrasystole modification (DAEM), respectively. The proposed framework was applied to real RRI data with PVC and PAC. The result showed that AED achieved a sensitivity of 93% and a false positive rate of 0.08 times per hour. The root mean squared error of the modified RRI decreased to 31% in PVC and 73% in PAC from the original RRI data by DAEM. In addition, the proposed framework was validated through application to a clinical epileptic seizure problem, which showed that it correctly suppressed the false positives caused by PVC. Thus, the proposed framework can contribute to realizing accurate HRV-based health monitoring and medical sensing systems.


Assuntos
Complexos Cardíacos Prematuros , Eletrocardiografia , Algoritmos , Complexos Cardíacos Prematuros/diagnóstico , Frequência Cardíaca , Humanos , Redes Neurais de Computação
10.
Chem Pharm Bull (Tokyo) ; 69(6): 548-556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34078801

RESUMO

Soft sensors play a crucial role as process analytical technology (PAT) tools. They are classified into physical models, statistical models, and their hybrid models. In general, statistical models are better estimators than physical models. In this study, two types of standard statistical models using process parameters (PPs) and near-infrared spectroscopy (NIRS) were investigated in terms of prediction accuracy and development cost. Locally weighted partial least squares regression (LW-PLSR), a type of nonlinear regression method, was utilized. Development cost was defined as the cost of goods required to construct an accurate model of commercial-scale equipment. Eleven granulation lots consisting of three laboratory-scale, two pilot-scale, and six commercial-scale lots were prepared. Three commercial-scale granulation lots were selected as a validation dataset, and the remaining eight granulation lots were utilized as calibration datasets. The results demonstrated that the PP-based and NIRS-based LW-PLSR models achieved high prediction accuracy without using the commercial-scale data in the calibration dataset. This practical case study clarified that the construction of accurate LW-PLSR models requires the calibration samples with the following two features: 1) located near the validation samples on the subspace spanned by principal components (PCs), and 2) having a wide range of variations in PC scores. In addition, it was confirmed that the reduction in cost and mass fraction of active pharmaceutical ingredient (API) made the PP-based models more cost-effective than the NIRS-based models. The present work supports to build accurate models efficiently and save the development cost of PAT.


Assuntos
Modelos Estatísticos , Preparações Farmacêuticas/química , Água/química , Química Farmacêutica/economia , Composição de Medicamentos/economia , Análise dos Mínimos Quadrados , Espectroscopia de Luz Próxima ao Infravermelho/economia
11.
Asian J Pharm Sci ; 16(2): 253-262, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33995618

RESUMO

We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing. The control and management of the Loss in Weight (LIW) feeder were deemed the most important, and the Residence Time Distribution (RTD) model were regarded effective for setting the control range and for controlling of the LIW feeder. Based on these ideas, the concept of process control using RTD was summarized. The presented contents can serve as a solid fundament for adopting a new control method of continuous direct compression processes in and beyond the Japanese market.

12.
Front Public Health ; 9: 630640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777884

RESUMO

The present study investigates the factors of "Weekday sleep debt (WSD)" by comparing activity data collected from persons with and without WSD. Since it has been reported that the amount of sleep debt as well the difference between the social clock and the biological clock is associated with WSD, specifying the factors of WSD other than chronotype may contribute to sleep debt prevention. We recruited 324 healthy male employees working at the same company and collected their 1-week wrist actigraphy data and answers to questionnaires. Because 106 participants were excluded due to measurement failure of the actigraphy data, the remaining 218 participants were included in the analysis. All participants were classified into WSD or non-WSD groups, in which persons had WDS if the difference between their weekend sleep duration and the mean weekday sleep duration was more than 120 min. We evaluated multiple measurements derived from the collected actigraphy data and trained a classifier that predicts the presence of WSD using these measurements. A support vector machine (SVM) was adopted as the classifier. In addition, to evaluate the contribution of each indicator to WSD, permutation feature importance was calculated based on the trained classifier. Our analysis results showed significant importance of the following three out of the tested 32 factors: (1) WSD was significantly related to persons with evening tendency. (2) Daily activity rhythms and sleep were less stable in the WSD group than in the non-WSD group. (3) A specific day of the week had the highest importance in our data, suggesting that work habit contributes to WSD. These findings indicate some WSD factors: evening chronotype, instability of the daily activity rhythm, and differences in work habits on the specific day of the week. Thus, it is necessary to evaluate the rhythms of diurnal activities as well as sleep conditions to identify the WSD factors. In particular, the diurnal activity rhythm influences WSD. It is suggested that proper management of activity rhythm may contribute to the prevention of sleep debt.


Assuntos
Actigrafia , Privação do Sono , Ritmo Circadiano , Hábitos , Humanos , Masculino , Sono
13.
Sleep Breath ; 25(4): 1821-1829, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33423183

RESUMO

PURPOSE: Sleep apnea syndrome (SAS) is a prevalent sleep disorder in which apnea and hypopnea occur frequently during sleep and result in increase of the risk of lifestyle-related disease development as well as daytime sleepiness. Although SAS is a common sleep disorder, most patients remain undiagnosed because the gold standard test polysomnography (PSG), is high-cost and unavailable in many hospitals. Thus, an SAS screening system that can be used easily at home is needed. METHODS: Apnea during sleep affects changes in the autonomic nervous function, which causes fluctuation of the heart rate. In this study, we propose a new SAS screening method that combines heart rate measurement and long short-term memory (LSTM) which is a type of recurrent neural network (RNN). We analyzed the data of intervals between adjacent R waves (R-R interval; RRI) on the electrocardiogram (ECG) records, and used an LSTM model whose inputs are the RRI data is trained to discriminate the respiratory condition during sleep. RESULTS: The application of the proposed method to clinical data showed that it distinguished between patients with moderate-to-severe SAS with a sensitivity of 100% and specificity of 100%, results which are superior to any other existing SAS screening methods. CONCLUSION: Since the RRI data can be easily measured by means of wearable heart rate sensors, our method may prove to be useful as an SAS screening system at home.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca/fisiologia , Aprendizado de Máquina , Redes Neurais de Computação , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
14.
Chem Pharm Bull (Tokyo) ; 69(2): 211-217, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33298636

RESUMO

As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.


Assuntos
Formas de Dosagem , Composição de Medicamentos/métodos , Administração Oral , Formas de Dosagem/normas , Composição de Medicamentos/normas , Indústria Manufatureira/normas , Controle de Qualidade
15.
Front Neurol ; 11: 567984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329309

RESUMO

Background: Orthostatic hypotension (OH) caused by autonomic dysfunction is a common symptom in older people and patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The orthostatic challenge test is a standard autonomic function test that measures a decrease of blood pressure during a postural change from supine to standing positions. Although previous studies have reported that changes in heart rate variability (HRV) are associated with autonomic dysfunction, no study has investigated the relationship between HRV before standing and the occurrence of OH in an orthostatic challenge test. This study aims to examine the connection between HRV in the supine position and the occurrence of OH in an orthostatic challenge test. Methods: We measured the electrocardiograms of patients with iRBD and healthy older people during an orthostatic challenge test, in which the supine and standing positions were held for 15 min, respectively. The subjects were divided into three groups: healthy controls (HC), OH-negative iRBD [OH (-) iRBD], and OH-positive iRBD [OH (+) iRBD]. HRV measured in the supine position during the test were calculated by time-domain analysis and Poincaré plots to evaluate the autonomic dysfunction. Results: Forty-two HC, 12 OH (-) iRBD, and nine OH (+) iRBD subjects were included. HRV indices in the OH (-) and the OH (+) iRBD groups were significantly smaller than those in the HC group. The multivariate logistic regression analysis for OH identification for the iRBD groups showed the model whose inputs were the HRV indices, i.e., standard deviation 2 (SD2) and the percentage of adjacent intervals that varied by more than 50 ms (pNN50), had a receiver operating characteristic curve with area under the curve of 0.840, the sensitivity to OH (+) of 1.000, and the specificity to OH (-) of 0.583 (p = 0.023). Conclusions: This study showed the possibility that short-term HRV indices in the supine position would predict subsequent OH in iRBD patients. Our results are of clinical importance in terms of showing the possibility that OH can be predicted using only HRV in the supine position without an orthostatic challenge test, which would improve the efficiency and safety of testing.

16.
Chem Pharm Bull (Tokyo) ; 68(9): 855-863, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879226

RESUMO

In-line monitoring of granule water content during fluid bed granulation is important to control drug product qualities. In this study, a practical scale-free soft sensor to predict water content was proposed to cope with the manufacturing scale changes in drug product development. The proposed method exploits two key ideas to construct a scale-free soft sensor. First, to accommodate the changes in the manufacturing scale, the process parameters (PPs) that are critical to water content at different manufacturing scales were selected as input variables. Second, to construct an accurate statistical model, locally weighted partial least squares regression (LW-PLSR), which can cope with collinearity and nonlinearity, was utilized. The soft sensor was developed using both laboratory (approx. 4 kg) data and pilot (approx. 25 kg) scale data, and the prediction accuracy in the commercial (approx. 100 kg) scale was evaluated based on the assumption that the process was scaled-up from the pilot scale to the commercial scale. The developed soft sensor exhibited a high prediction accuracy, which was equivalent to the commonly used near-infrared (NIR) spectra-based method. The proposed method requires only standard instruments; therefore, it is expected to be a cost-effective alternative to the NIR spectra-based method.


Assuntos
Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Água/química
17.
Sensors (Basel) ; 20(14)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32709064

RESUMO

A warning prior to seizure onset can help improve the quality of life for epilepsy patients. The feasibility of a wearable system for predicting epileptic seizures using anomaly detection based on machine learning is evaluated. An original telemeter is developed for continuous measurement of R-R intervals derived from an electrocardiogram. A bespoke smartphone app calculates the indices of heart rate variability in real time from the R-R intervals, and the indices are monitored using multivariate statistical process control by the smartphone app. The proposed system was evaluated on seven epilepsy patients. The accuracy and reliability of the R-R interval measurement, which was examined in comparison with the reference electrocardiogram, showed sufficient performance for heart rate variability analysis. The results obtained using the proposed system were compared with those obtained using the existing video and electroencephalogram assessments; it was noted that the proposed method has a sensitivity of 85.7% in detecting heart rate variability change prior to seizures. The false positive rate of 0.62 times/h was not significantly different from the healthy controls. The prediction performance and practical advantages of portability and real-time operation are demonstrated in this study.


Assuntos
Epilepsia , Dispositivos Eletrônicos Vestíveis , Adolescente , Adulto , Criança , Eletroencefalografia , Epilepsia/diagnóstico , Frequência Cardíaca , Humanos , Aprendizado de Máquina , Qualidade de Vida , Reprodutibilidade dos Testes , Convulsões/diagnóstico , Adulto Jovem
18.
Front Public Health ; 8: 178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509717

RESUMO

A considerable amount of health record (HR) data has been stored due to recent advances in the digitalization of medical systems. However, it is not always easy to analyze HR data, particularly when the number of persons with a target disease is too small in comparison with the population. This situation is called the imbalanced data problem. Over-sampling and under-sampling are two approaches for redressing an imbalance between minority and majority examples, which can be combined into ensemble algorithms. However, these approaches do not function when the absolute number of minority examples is small, which is called the extremely imbalanced and small minority (EISM) data problem. The present work proposes a new algorithm called boosting combined with heuristic under-sampling and distribution-based sampling (HUSDOS-Boost) to solve the EISM data problem. To make an artificially balanced dataset from the original imbalanced datasets, HUSDOS-Boost uses both under-sampling and over-sampling to eliminate redundant majority examples based on prior boosting results and to generate artificial minority examples by following the minority class distribution. The performance and characteristics of HUSDOS-Boost were evaluated through application to eight imbalanced datasets. In addition, the algorithm was applied to original clinical HR data to detect patients with stomach cancer. These results showed that HUSDOS-Boost outperformed current imbalanced data handling methods, particularly when the data are EISM. Thus, the proposed HUSDOS-Boost is a useful methodology of HR data analysis.


Assuntos
Algoritmos , Análise de Dados , Humanos , Sistemas Computadorizados de Registros Médicos
19.
IEEE Trans Neural Syst Rehabil Eng ; 28(2): 390-398, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31944960

RESUMO

Sleep spindles are important electroencephalographic (EEG) waveforms in sleep medicine; however, it is burdensome even for experts to detect spindles, so automatic spindle detection methodologies have been investigated. Conventional methods utilize waveforms template matching or machine learning for detecting spindles. In the former approach, it is necessary to tune thresholds for individual adaptation, while the latter approach has the problem of imbalanced data because the amount of sleep spindles is small compared with the entire EEG data. The present work proposes a sleep spindle detection method that combines wavelet synchrosqueezed transform (SST) and random under-sampling boosting (RUSBoost). SST is a time-frequency analysis method suitable for extracting features of spindle waveforms. RUSBoost is a framework for coping with the imbalanced data problem. The proposed SST-RUS can deal with the imbalanced data in spindle detection and does not require threshold tuning because RUSBoost uses majority voting of weak classifiers for discrimination. The performance of SST-RUS was validated using an open-access database called the Montreal archives of sleep studies cohort 1 (MASS-C1), which showed an F-measure of 0.70 with a sensitivity of 76.9% and a positive predictive value of 61.2%. The proposed method can reduce the burden of PSG scoring.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Fases do Sono/fisiologia , Análise de Ondaletas , Adolescente , Adulto , Algoritmos , Bases de Dados Factuais , Feminino , Humanos , Aprendizado de Máquina , Masculino , Polissonografia/métodos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Adulto Jovem
20.
Physiol Meas ; 40(12): 125001, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726434

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a common sleep disorder; however, most patients are undiagnosed and untreated because it is difficult for patients themselves to notice OSA in daily living. Polysomnography (PSG), which is the gold standard test for sleep disorder diagnosis, cannot be performed in many hospitals. This fact motivates us to develop a simple system for screening OSA at home. APPROACH: The autonomic nervous system changes during apnea, and such changes affect heart rate variability (HRV). This work develops a new apnea screening method based on HRV analysis and machine learning technologies. An apnea/normal respiration (A/N) discriminant model is built for respiration condition estimation for every heart rate measurement, and an apnea/sleep ratio is introduced for final diagnosis. A random forest is adopted for the A/N discriminant model construction, which is trained with the PhysioNet apnea-ECG database. MAIN RESULTS: The screening performance of the proposed method was evaluated by applying it to clinical PSG data. Sensitivity and specificity achieved 76% and 92%, respectively, which are comparable to existing portable sleep monitoring devices used in sleep laboratories. SIGNIFICANCE: Since the proposed OSA screening method can be used more easily than existing devices, it will contribute to OSA treatment.


Assuntos
Frequência Cardíaca , Programas de Rastreamento , Respiração , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Estudos de Casos e Controles , Análise Discriminante , Feminino , Humanos , Masculino , Polissonografia , Adulto Jovem
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