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1.
Bioengineered ; 12(1): 310-324, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33446013

RESUMO

In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren's syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3+ T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS.

2.
Cost Eff Resour Alloc ; 18: 33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32944005

RESUMO

Background: This study aimed to examine the cost-effectiveness of one-time standard endoscopic screening with Lugol's iodine staining for esophageal cancer (EC) in China. Methods: A Markov decision analysis model with eleven states was built. Individuals aged 40 to 69 years were classified into six age groups in five-year intervals. Three different strategies were adopted for each cohort: (1) no screening; (2) one-time endoscopic screening with Lugol's iodine staining with an annual follow-up for low-grade intraepithelial neoplasia (LGIN); and (3) one-time endoscopic screening with Lugol's iodine staining without follow-up. Quality-adjusted life-years (QALYs) indicated the effectiveness of the model. The incremental cost-effectiveness ratio (ICER) was used as the evaluation indicator. Sensitivity analysis was performed to assess the robustness of the model. Results: One-time screening with follow-up was the undominated strategy for individuals aged 40-44 and 45-49 years, which saved USD 10,942.57 and USD 6611.73 per QALY gained compared to nonscreening strategy. For those aged 50-69 years, the nonscreening scenarios were undominated. One-time screening without follow-up was the extended dominated strategy. Compared to screening strategies without follow-up, all the screening strategies with follow-up were more cost-effective, with the ICER increasing from 299.57 USD/QALY for individuals aged 40-44 years to 1617.72 USD/QALY for individuals aged 65-69 years. Probabilistic sensitivity analysis (PSA) supported the results of the base case analysis. Conclusions: One-time EC screening with follow-up targeting individuals aged 40-49 years was the most cost-effective strategy.

3.
Gland Surg ; 9(4): 968-984, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953606

RESUMO

Background: This study described the incidence and mortality trends and analyzed age-period-cohort effects on incidences in China, Japan, and Korea. Methods: Data were extracted from the Cancer Incidence in Five Continents series and the World Health Organization Cancer Mortality Database, and the age-standardized incidence and mortality rates by Segi's world population were calculated. Joinpoint regression analysis was used to evaluate the time trend of age-standardized incidence and mortality rates and the age-period-cohort model with intrinsic estimator was applied for estimating the effects of age, period, and cohort on thyroid cancer (TC) incidence in individuals between 20 and 84 years of age. Results: An increasing trend in TC incidence rates was observed among males from China (10.3%), Japan (4.7%), and Korea (20.8%) and among females from China (9.4%), Japan (3.5%), and Korea (20.5%). TC incidence rates in females were much higher than those in males. A downward trend of TC mortality rates was observed, especially in both sexes of Japan and Chinese females. The slope of the age effect curve peaked at an earlier age in females than males in Japan and Korea. A strong period effect and remarkedly increasing rate ratios were observed in all regions and for both sexes. The cohort effect had a declining tendency on TC incidence in males and females in these areas. Conclusions: The rapidly upward incidence trend and strong period effect suggest that overdiagnosis caused by higher diagnostic intensity might be an explanation for the upward trend, and some environmental risk factor exposures are also not excluded. In addition, the discrepant trends of TC incidence and mortality reveal the need to identify the few high-risk patients who needed further treatment from those patients who may not need treatment.

4.
J Org Chem ; 85(17): 11331-11339, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32786629

RESUMO

A simple chiral primary-tertiary diamine derived from C2-symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N-sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N-sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N-heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

5.
Comput Methods Programs Biomed ; 196: 105574, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32540776

RESUMO

BACKGROUND AND OBJECTIVE: Blood glucose levels in humans change over time. Continuous glucose monitoring system (CGMS), can constantly monitor the change of blood glucose concentration. Given the historical data of blood glucose, predicting the trend of blood glucose in a short term is important for diabetes. Appropriate behaviors can be adopted to prevent hypoglycemia or hyperglycemia. METHODS: The method proposed in this paper only uses historical blood glucose data as input, rather than complex multi-dimensional input. Previous articles have demonstrated that canonical correlation analysis (CCA) can effectively predict blood glucose. The linear relationship between historical blood glucose values and predicted values was only considered regrettably. To compensate for this, this paper adds a kernel function to find out the non-linear relationship between blood glucose. In the introduced kernel function, some parameters need to be adjusted. To reduce the deviation caused by manual parameter adjustment, this paper discusses the role of particle swarm optimization (PSO). Besides, this article puts forward an error compensation for CCA to enhance the precision. Finally based on the prediction results of PSO-KCCA, a personalized hypoglycemic warning threshold is proposed. RESULTS: The proposed method is validated using clinical data by the root mean square error (RMSE) and differential coefficient (R2). The average RMSE result in PSO-KCCA was 8.01, 11.98, 12.45, 13.23, 14.53, 16.40 mg/dL in prediction horizon (PH) =5, 10, 15, 20, 25, 30 min. The average R2 was 0.95, 0.95, 0.98, 0.97, 0.98, and 0.97, respectively. The CCA with error compensation (EC-CCA) reduced RMSE by 33.45% compared with CCA. For the hypoglycemic warning, the average sensitivity obtained at 6 different PH values was 94.37%, and the specificity was 92.25%. CONCLUSIONS: The experimental results confirm the effectiveness of PSO-KCCA in blood glucose prediction. The proposed EC-CCA successfully reduces the delay in the time series prediction. The personalized hypoglycemic warning threshold consider the influence of the model accuracy on the prediction results. This method guarantees the rate of underreporting during monitoring and ensures patient safety.

6.
Comput Methods Programs Biomed ; 191: 105416, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32146213

RESUMO

BACKGROUND AND OBJECTIVES: Glycemic control with unannounced meals is the major challenge for artificial pancreas. In this study, we described the performance and safety of learning-type model predictive control (L-MPC) for artificial pancreas challenged by an unannounced meal in type 1 diabetes (T1D). METHODS: This closed-loop (CL) system was tested in 29 T1D patients at one site in a 4 h inpatient open-label study. Participants used an L-MPC CL system for 6 days after 2-day system identification using open-loop (OL) insulin system. During the CL period, the L-MPC system was started from 8:00 am to noon each day. At 9:00 am, each participant consumed 50 g of carbohydrates with no prandial insulin bolus. At 9:30 am on CL-Day 4 or CL-Day 6, participants rode bicycles for 20 minutes or drank 50 ml of beer, in a random order. RESULTS: As the primary outcome, TIR on CL-Day 3 was 65.2±23.3%, which was 9.8 points higher (95% CI 1.8 to 17.8; P = 0.019) than that on CL-Day 1. The time of glucose >10 mmol/L was decreased by 11.0% (95% CI -18.7 to 3.3; P = 0.007), and mean glucose level was decreased by 1.1 mmol/L (95% CI -1.1 to 0.5; P = 0.000). The total daily insulin dosage showed no significant difference (-0.1U, 95% CI -1.34 to 1.32; P = 0.982). Compared with OL-Day1 with a postprandial bolus, the TIR was increased by 13.7 points (95% CI 1.4 to 26.0; P = 0.030), the time of glucose >10 mmol/L and the mean glucose level were also decreased. Compared with the exercise day (CL-Day E, 62.0 ± 23.3%; P = 0.347) or alcohol day (CL-Day A, 64.0 ± 23.6%; P = 0.756), there was no statistically significant difference in terms of TIR, time of glucose >10 mmol/L and mean glucose level. No severe hypoglycemic events occurred and hypoglycemic episodes were not increased by using closed-loop insulin system. CONCLUSION: The L-MPC CL insulin system achieved good glycemic control challenged by an unannounced meal.

7.
Thorac Cancer ; 11(4): 1076-1089, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130756

RESUMO

BACKGROUND: We aimed to obtain a set of health state utility scores of patients with esophageal cancer (EC) and precancerous lesions in China, and to explore the influencing factors of health-related quality of life (HRQoL). METHODS: A hospital-based multicenter cross-sectional study was conducted. From 2013 to 2014, patients with EC or precancerous lesions were enrolled. HRQoL was assessed using a European quality of life-5 dimension (EQ-5D-3L) instrument. Multivariable linear regression analysis was performed to explore the influencing factors of the EQ-5D utility scores. RESULTS: A total of 2090 EC patients and 156 precancer patients were included in the study. The dimension of pain/discomfort had the highest rate of self-reported problems, 60.5% in EC and 51.3% in precancer patients. The mean visual analog scale (VAS) score for EC and precancer patients were 68.4 ± 0.7 and 64.5 ± 3.1, respectively. The EQ-5D utility scores for EC and precancer patients were estimated as 0.748 ± 0.009 and 0.852 ± 0.022, and the scores of EC at stage I, stage II, stage III, and stage IV were 0.693 ± 0.031, 0.747 ± 0.014, 0.762 ± 0.015, and 0.750 ± 0.023, respectively. According to the multivariable analyses, the factors of region, occupation, household income in 2012, health care insurance type, pathological type, type of therapy, and time points of the survey were statistically associated with the EQ-5D utility scores of EC patients. CONCLUSIONS: There were remarkable decrements of utility scores among esophageal cancer patients, compared with precancer patients. The specific utility scores of EC would support further cost-utility analysis in populations in China.

8.
Chem Commun (Camb) ; 56(10): 1553-1556, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31930267

RESUMO

An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20 : 1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.

9.
Comput Methods Programs Biomed ; 186: 105224, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31765937

RESUMO

BACKGROUND AND OBJECTIVE: In intensive care units (ICUs), length of stay (LOS) prediction is critical to help doctors and nurses select appropriate treatment options and predict patients' condition. Considering that most hospitals use universal models to predict patients' condition, which cannot meet the individual needs of special ICU patients. Our goal is to create a personalized model for patients to determine the number of hospital stays. METHODS: In this study, a new combination of just-in-time learning (JITL) and one-class extreme learning machine (one-class ELM) is proposed to predict the number of days a patient stays in hospital. This combination is shortened as one-class JITL-ELM, where JITL is used to search for personalized cases for a new patient and one-class ELM is used to determine whether the patient can be discharged within 10 days. RESULTS: The experimental results show that the one-class JITL-ELM model has an area under the curve (AUC) index of 0.8510, lift value of 2.1390, precision of 1, and G-mean is 0.7842. Its accuracy, specificity, and sensitivity were found as 0.82, 1, and 0.6150, respectively. Moreover, a novel simple mortality risk level estimation system that can determine the mortality rate of a patient by combining LOS and age is proposed. It has an accuracy rate of 66% and the miss rate of only 6.25%. CONCLUSIONS: Overall, the one-class JITL-ELM can accurately predict hospitalization days and mortality using early physiological parameters. Moreover, a simple mortality risk level estimation system based on a combination of LOS and age is proposed; the system is simple, highly interpretable, and has strong application value.

10.
Chin J Cancer Res ; 31(1): 144-151, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30996572

RESUMO

Objective: To analyze the incidence and mortality rates of thyroid cancer (TC) in China from 2008 to 2012. Methods: Incident and death cases of TC were retrieved from the National Central Cancer Registry (NCCR) database collecting from 135 cancer registries in China during 2008-2012. The crude incidence and mortality rates of TC were calculated by area (urban/rural), region (eastern, middle, western), gender and age group (0, 1-4, 5-9, …, 85+). China census in 2000 and world Segi's population were applied for age-standardized rates. Joinpoint (Version 4.6.0.0) model was used for time-trend analysis. Results: The crude incidence rate of TC was 7.56/100,000 which ranked the seventh in overall cancers. The age-standardized incidence rates by China population (ASIRC) and by World population (ASIRW) were 6.25/100,000 and 5.52/100,000, respectively. The crude mortality of TC in China was 0.52/100,000. The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 0.34/100,000 and 0.32/100,000, respectively. Incidence and mortality rates of TC were higher in females than in males and higher in urban areas than in rural areas. Eastern areas had the highest incidence followed by middle and western areas. TC incidence increased dramatically after age of 15 years, then peaked at 14.08/100,000 in the group of 50-54 years and finally decreased sharply after 55 years old. TC mortality increased with age in population, reaching the peak of 5.09/100,000 in sub-population aged 85 years or older. TC incidence increased by 4.73 times from 2.40/100,000 in 2003 to 13.75/100,000 in 2012 with an average annual increase of 20%, while TC mortality only increased slightly around 0.32/100,000 from 0.26/100,000 to 0.36/100,000. Conclusions: Appropriate targeted prevention, early detection and treatment programs can be carried out to curb the rapid growth trend of TC and control the disease burden.

11.
Chemosphere ; 219: 383-389, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30551104

RESUMO

Oilfield sludge is recognized as a hazardous solid waste in China because of its considerable hydrocarbon content and other toxic components. In this study, the nitrogen transformation during pyrolysis of typical oil sludge samples produced in the Daqing oilfield (the largest oilfield in China), was experimentally investigated. X-ray photoelectron spectroscopy (XPS) and thermos gravimetric (TG) were used in laboratory-scale experiments and batch pyrolysis experiments were conducted at 200-800 °C in a tubular reactor to obtain quantitative information on the change of nitrogen conversion in the char, tar, and gas fractions. The thermal decomposition of amine-N compounds contributed to NH3 release below 250 °C. However, the amine-N compounds in the char were converted to amine-N and imine-N compounds in the tar, and no obvious nitrogenous gases were found when the temperature increased from 250 to 500 °C. Between 500 and 800 °C, a large amount of NH3 and a small portion of HCN were found owing to the secondary cracking of tar and ring opening of heterocyclic-N compounds in the char. Therefore, NH3, HCN, and NO emissions can be reduced by accurate control of the pyrolysis temperature. A temperature of 400 °C was determined to be the optimal temperature for oilfield sludge pyrolysis, with 24.5% residual char and 43.0% tar produced. The results indicated that a suitable oilfield sludge pyrolysis temperature is helpful for reducing nitrogenous pollutant emissions, volume reduction, and energy recovery, which are beneficial for environmentally friendly production practices.


Assuntos
Nitrogênio/química , Campos de Petróleo e Gás/química , Polímeros/análise , Pirólise , Esgotos/química , China , Resíduos Perigosos/análise , Temperatura Alta , Nitrogênio/análise , Espectroscopia Fotoeletrônica
12.
BMC Psychiatry ; 18(1): 115, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703173

RESUMO

BACKGROUND: Life event assessment is an important part in psychological autopsy, and how to integrate its proxy data from two informants is a major methodological issue which needs solving. METHODS: Totally 416 living subjects and their two informants were interviewed by psychological autopsy, and life events were assessed with Paykel's Interview for Recent Life Events. Validities of integrated proxy data using six psychological autopsy information reconstruction methods were evaluated, with living subjects' self-reports used as gold-standard criteria. RESULTS: For all the life events, average value of Youden Indexes for proxy data by type C information reconstruction method (choosing positive value from two informants) was larger than other five methods'. For family life related events, proxy data by type 1st information reconstruction method were not significantly different from living subjects' self-reports (P = 0.828). For all other life events, proxy data by type C information reconstruction method were not significantly different from the gold-standard. CONCLUSIONS: Choosing positive value is a relatively better method for integrating dichotomous (positive vs. negative) proxy data from two informants in life event assessment in psychological autopsy, except for family life related events. In that case, using information provided by 1st informants (mainly family member) is recommended.


Assuntos
Família/psicologia , Entrevista Psicológica , Procurador/psicologia , Suicídio/psicologia , Inquéritos e Questionários , Adolescente , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Suicídio/estatística & dados numéricos , Adulto Jovem
13.
BMC Cancer ; 18(1): 291, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29544469

RESUMO

BACKGROUND: Thyroid cancer is the most common malignant disease of the endocrine system. Previous studies indicate a rapid increase in the incidence of thyroid cancer in recent decades, and this increase has aroused the great public concern. The aim of this study was to analyze the trends in incidence, mortality and clinical-pathological patterns of thyroid cancer in Zhejiang province. METHODS: Population-based incidence and mortality rates of thyroid cancer were collected from eight cancer registries in Zhejiang from 2000 to 2012. The incidence and mortality rates were age-standardized to Segi's world population. A Joinpoint model was used to examine secular trends in age-adjusted thyroid cancer rates with the Joinpoint Regression Program Version 4.0.0. Thyroid cancer patients were recruited from Zhejiang Cancer Hospital from 1972 to 2014. Patient demographics, tumor histology and tumor size were compared among the different periods of 1972-1985, 1986-1999 and 2000-2014. RESULTS: The age-standardized incidence rate of thyroid cancer in Zhejiang cancer registries was 2.75/105 in 2000, and increased to 19.42/105 in 2012. Additionally, we observed significantly increasing incidence rates with the Annual Percent Change (APC) of 22.86% (95%CI, 19.2%-26.7%). The age-standardized mortality of thyroid cancer in Zhejiang cancer registries was 0.23/105 in 2000 and 0.25/105 in 2012. No significant change in mortality rate was found. We observed a rapid increase in the proportions of papillary thyroid carcinoma (PTC) in 12,508 patients with thyroid carcinoma identified in the Zhejiang Cancer Hospital from 1972 to 2014 while the proportions of poorly differentiated thyroid cancer (PDTC), medullary thyroid carcinoma (MTC) and follicular thyroid carcinoma (FTC) decreased over the decades. In the PTC cases, the proportion of patients with maximum tumor diameter (MTD) < 1 cm dramatically and significantly increased from 0 in 1972-1985 to 32.1% in 2000-2014. CONCLUSIONS: A rapid increase in incidence and a stable trend in mortality of thyroid cancer were found in the distribution of thyroid cancer. Most of the increased incidence was PTC, especially the papillary thyroid microcarcinoma (PTMC) with MTD < 1 cm. This increase in incidence might be due to increased diagnosis with advanced technology.


Assuntos
Mortalidade/tendências , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/mortalidade , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adulto , Fatores Etários , Carcinoma Medular/epidemiologia , Carcinoma Medular/mortalidade , Carcinoma Medular/patologia , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores Sexuais , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
14.
Comput Methods Programs Biomed ; 156: 61-71, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29428077

RESUMO

BACKGROUND AND OBJECTIVES: Intelligent status monitoring for critically ill patients can help medical stuff quickly discover and assess the changes of disease and then make appropriate treatment strategy. However, general-type monitoring model now widely used is difficult to adapt the changes of intensive care unit (ICU) patients' status due to its fixed pattern, and a more robust, efficient and fast monitoring model should be developed to the individual. METHODS: A data-driven learning approach combining locally weighted projection regression (LWPR) and principal component analysis (PCA) is firstly proposed and applied to monitor the nonlinear process of patients' health status in ICU. LWPR is used to approximate the complex nonlinear process with local linear models, in which PCA could be further applied to status monitoring, and finally a global weighted statistic will be acquired for detecting the possible abnormalities. Moreover, some improved versions are developed, such as LWPR-MPCA and LWPR-JPCA, which also have superior performance. RESULTS: Eighteen subjects were selected from the Physiobank's Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) database, and two vital signs of each subject were chosen for online monitoring. The proposed method was compared with several existing methods including traditional PCA, Partial least squares (PLS), just in time learning combined with modified PCA (L-PCA), and Kernel PCA (KPCA). The experimental results demonstrated that the mean fault detection rate (FDR) of PCA can be improved by 41.7% after adding LWPR. The mean FDR of LWPR-MPCA was increased by 8.3%, compared with the latest reported method L-PCA. Meanwhile, LWPR spent less training time than others, especially KPCA. CONCLUSIONS: LWPR is first introduced into ICU patients monitoring and achieves the best monitoring performance including adaptability to changes in patient status, sensitivity for abnormality detection as well as its fast learning speed and low computational complexity. The algorithm is an excellent approach to establishing a personalized model for patients, which is the mainstream direction of modern medicine in the following development, as well as improving the global monitoring performance.


Assuntos
Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Monitorização Ambulatorial/métodos , Idoso , Algoritmos , Estado Terminal , Processamento Eletrônico de Dados , Feminino , Nível de Saúde , Humanos , Análise dos Mínimos Quadrados , Modelos Lineares , Aprendizado de Máquina , Masculino , Informática Médica , Pessoa de Meia-Idade , Análise de Componente Principal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Sinais Vitais
15.
Org Biomol Chem ; 15(40): 8669-8679, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28990625

RESUMO

N,N'-Dialkylbarbituric acids as cyclic malonamide donors were successfully used in the enantioselective Michael addition reaction of enones. Using cinchona alkaloid-based bifunctional squaramide as an organocatalyst, this Michael reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective (91-99% ee) production of the corresponding optically active 5-substituted barbituric acid derivatives. The transformations of the Michael product for the barbituric acid structural unit were realized in two ways, deprotection to remove the N-tert-butyl group and alkylation to produce 5,5-disubstituted barbituric acid derivatives.


Assuntos
Barbitúricos/química , Alcaloides de Cinchona/química , Cetonas/química , Quinina/análogos & derivados , Barbitúricos/síntese química , Catálise , Conformação Molecular , Quinina/química , Estereoisomerismo
16.
J Diabetes Sci Technol ; 11(6): 1112-1123, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28728434

RESUMO

BACKGROUND: Blood glucose (BG) regulation is a long-term task for people with diabetes. In recent years, more and more researchers have attempted to achieve automated regulation of BG using automatic control algorithms, called the artificial pancreas (AP) system. In clinical practice, it is equally important to guarantee the treatment effect and reduce the treatment costs. The main motivation of this study is to reduce the cure burden. METHODS: The dynamic R-parameter economic model predictive control (R-EMPC) is chosen to regulate the delivery rates of exogenous hormones (insulin and glucagon). It uses particle swarm optimization (PSO) to optimize the economic cost function and the switching logic between insulin delivery and glucagon delivery is designed based on switching control theory. RESULTS: The proposed method is first tested on the standard subject; the result is compared with the switching PID and the switching MPC. The effect of the dynamic R-parameter on improving the control performance is illustrated by comparing the results of the EMPC and the R-EMPC. Finally, the robustness tests on meal change (size and timing), hormone sensitivity (insulin and glucagon), and subject variability are performed. All results show that the proposed method can improve the control performance and reduce the economic costs. CONCLUSIONS: The simulation results verify the effectiveness of the proposed algorithm on improving the tracking performance, enhancing robustness, and reducing economic costs. The method proposed in this study owns great worth in practical application.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/economia , Custos de Medicamentos , Glucagon/administração & dosagem , Glucagon/economia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Sistemas de Infusão de Insulina/economia , Insulina/administração & dosagem , Insulina/economia , Pâncreas Artificial/economia , Algoritmos , Biomarcadores/sangue , Glicemia/metabolismo , Automonitorização da Glicemia/economia , Simulação por Computador , Redução de Custos , Análise Custo-Benefício , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Glucagon/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Modelos Biológicos , Modelos Econômicos , Pâncreas Artificial/efeitos adversos , Período Pós-Prandial , Valor Preditivo dos Testes , Processamento de Sinais Assistido por Computador , Fatores de Tempo , Resultado do Tratamento
17.
Diabetes Technol Ther ; 19(1): 41-48, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28060528

RESUMO

BACKGROUND: A learning-type artificial pancreas has been proposed to exploit the repetitive nature in the blood glucose dynamics. We clinically evaluated the efficacy of the learning-type artificial pancreas. METHODS: We conducted a pilot clinical study in 10 participants of mean age 36.1 years (standard deviation [SD] 12.7; range 16-58) with type 1 diabetes. Each trial was conducted for eight consecutive mornings. The first two mornings were open-loop to obtain the individualized parameters. Then, the following six mornings were closed-loop, during which a learning-type model predictive control algorithm was employed to calculate the insulin infusion rate. To evaluate the algorithm's robustness, each participant took exercise or consumed alcohol on the fourth or sixth closed-loop day and the order was determined randomly. The primary outcome was the percentage of time spent in the target glucose range of 3.9-8.0 mmol/L between 0900 and 1200 h. RESULTS: The percentage of time with glucose spent in target range was significantly improved from 51.6% on day 1 to 71.6% on day 3 (mean difference between groups 17.9%, confidence interval [95% CI] 3.6-32.1; P = 0.020). There were no hypoglycemic episodes developed on day 3 compared with two episodes on day 1. There was no difference in the percentage of time with glucose spent in target range between exercise day versus day 5 and alcohol day versus day 5. CONCLUSIONS: The learning-type artificial pancreas system achieved good glycemic regulation and provided increased effectiveness over time. It showed a satisfactory performance even when the blood glucose was challenged by exercise or alcohol.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Retroalimentação Fisiológica , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pâncreas Artificial , Adolescente , Adulto , Algoritmos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
18.
Chem Asian J ; 11(21): 3118-3125, 2016 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-27616465

RESUMO

Aryl ketones represent problematic substrates for asymmetric Mannich reactions due to a large steric hindrance exhibited by such compound species. A highly enantioselective direct Mannich reaction of aryl methyl ketones with cyclic imine benzo[e][1,2,3]oxathiazine 2,2-dioxides could be successfully carried out utilizing a combination of cinchona alkaloid-derived primary amines with trifluoroacetic acid (TFA); the primary amines feature a superior catalytic efficacy over secondary amines with a variety of sterically hindered carbonyl compounds as substrates. The reaction proceeded well with various cyclic imines in 89-97 % ee and with various aryl methyl ketones in 85-98 % ee. Moreover, the aryl carbonyl of a Mannich product could be transformed to ketoxime, which further undergoes a Beckmann rearrangement to produce an amide compound while maintaining enantioselectivity.


Assuntos
Aminas/química , Alcaloides de Cinchona/química , Iminas/química , Cetonas/química , Tiazinas/química , Catálise , Conformação Molecular , Estereoisomerismo , Ácido Trifluoracético/química
19.
Sci Rep ; 6: 31609, 2016 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-27546611

RESUMO

Although several studies have evaluated the role of body weight as a risk factor for mortality, most studies have been conducted in Western populations and the findings remain controversial. We performed a prospective study to examine the association between body mass index (BMI) and all-cause mortality in Yinzhou District, Ningbo, China. At baseline, 384,533 subjects were recruited through the Yinzhou Health Information System between 2004 and 2009. The final analysis was restricted to 372,793 participants (178,333 men and 194,460 women) aged 18 years and older. Cox proportional hazards models were used to estimate hazard ratios(HRs) and 95% confidence intervals(CIs). We found an increased risk of all-cause mortality among individuals with BMI levels <22.5-24.9, although several groups were not statistically significant-adjusted HRs for persons with BMIs of <15.0, 15.0-17.4, 17.5-19.9, and 20.0-22.4 were 1.61(95% CI: 1.17-2.23), 1.07(0.94-1.20), 1.04(0.98-1.10), 1.06(1.02-1.11), respectively. In the upper BMI range, subjects with BMIs of 25.0-34.9 had a reduced risk of all-cause mortality. Sensitivity analyses excluding smokers, those with prevalent chronic disease or those with less than four years of follow-up did not materially alter these results. Our findings provide evidence for an inverse association of BMI and mortality in this population.


Assuntos
Índice de Massa Corporal , Mortalidade , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
J Clin Monit Comput ; 30(6): 807-820, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26392184

RESUMO

Offline general-type models are widely used for patients' monitoring in intensive care units (ICUs), which are developed by using past collected datasets consisting of thousands of patients. However, these models may fail to adapt to the changing states of ICU patients. Thus, to be more robust and effective, the monitoring models should be adaptable to individual patients. A novel combination of just-in-time learning (JITL) and principal component analysis (PCA), referred to learning-type PCA (L-PCA), was proposed for adaptive online monitoring of patients in ICUs. JITL was used to gather the most relevant data samples for adaptive modeling of complex physiological processes. PCA was used to build an online individual-type model and calculate monitoring statistics, and then to judge whether the patient's status is normal or not. The adaptability of L-PCA lies in the usage of individual data and the continuous updating of the training dataset. Twelve subjects were selected from the Physiobank's Multi-parameter Intelligent Monitoring for Intensive Care II (MIMIC II) database, and five vital signs of each subject were chosen. The proposed method was compared with the traditional PCA and fast moving-window PCA (Fast MWPCA). The experimental results demonstrated that the fault detection rates respectively increased by 20 % and 47 % compared with PCA and Fast MWPCA. L-PCA is first introduced into ICU patients monitoring and achieves the best monitoring performance in terms of adaptability to changes in patient status and sensitivity for abnormality detection.


Assuntos
Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Pacientes Internados , Aprendizagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Sistemas On-Line , Análise de Componente Principal , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Software
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