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1.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36682018

RESUMO

The determination of transcriptome profiles that mediate immune therapy in cancer remains a major clinical and biological challenge. Despite responses induced by immune-check points inhibitors (ICIs) in diverse tumor types and all the big breakthroughs in cancer immunotherapy, most patients with solid tumors do not respond to ICI therapies. It still remains a big challenge to predict the ICI treatment response. Here, we propose a framework with multiple prior knowledge networks guided for immune checkpoints inhibitors prediction-DeepOmix-ICI (or ICInet for short). ICInet can predict the immune therapy response by leveraging geometric deep learning and prior biological knowledge graphs of gene-gene interactions. Here, we demonstrate more than 600 ICI-treated patients with ICI response data and gene expression profile to apply on ICInet. ICInet was used for ICI therapy responses prediciton across different cancer types-melanoma, gastric cancer and bladder cancer, which includes 7 cohorts from different data sources. ICInet is able to robustly generalize into multiple cancer types. Moreover, the performance of ICInet in those cancer types can outperform other ICI biomarkers in the clinic. Our model [area under the curve (AUC = 0.85)] generally outperformed other measures, including tumor mutational burden (AUC = 0.62) and programmed cell death ligand-1 score (AUC = 0.74). Therefore, our study presents a prior-knowledge guided deep learning method to effectively select immunotherapy-response-associated biomarkers, thereby improving the prediction of immunotherapy response for precision oncology.


Assuntos
Melanoma , Neoplasias da Bexiga Urinária , Humanos , Reconhecimento Automatizado de Padrão , Medicina de Precisão , Melanoma/patologia , Imunoterapia/métodos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
2.
Brief Bioinform ; 23(6)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36124675

RESUMO

In common medical procedures, the time-consuming and expensive nature of obtaining test results plagues doctors and patients. Digital pathology research allows using computational technologies to manage data, presenting an opportunity to improve the efficiency of diagnosis and treatment. Artificial intelligence (AI) has a great advantage in the data analytics phase. Extensive research has shown that AI algorithms can produce more up-to-date and standardized conclusions for whole slide images. In conjunction with the development of high-throughput sequencing technologies, algorithms can integrate and analyze data from multiple modalities to explore the correspondence between morphological features and gene expression. This review investigates using the most popular image data, hematoxylin-eosin stained tissue slide images, to find a strategic solution for the imbalance of healthcare resources. The article focuses on the role that the development of deep learning technology has in assisting doctors' work and discusses the opportunities and challenges of AI.


Assuntos
Algoritmos , Inteligência Artificial , Humanos , Amarelo de Eosina-(YS)
3.
RNA Biol ; 21(1): 17-31, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39016036

RESUMO

It is likely that an RNA world existed in early life, when RNA played both the roles of the genome and functional molecules, thereby undergoing Darwinian evolution. However, even with only one type of polymer, it seems quite necessary to introduce a labour division concerning these two roles because folding is required for functional molecules (ribozymes) but unfavourable for the genome (as a template in replication). Notably, while ribozymes tend to have adopted a linear form for folding without constraints, a circular form, which might have been topologically hindered in folding, seems more suitable for an RNA template. Another advantage of involving a circular genome could have been to resist RNA's end-degradation. Here, we explore the scenario of a circular RNA genome plus linear ribozyme(s) at the precellular stage of the RNA world through computer modelling. The results suggest that a one-gene scene could have been 'maintained', albeit with rather a low efficiency for the circular genome to produce the ribozyme, which required precise chain-break or chain-synthesis. This strict requirement may have been relieved by introducing a 'noncoding' sequence into the genome, which had the potential to derive a second gene through mutation. A two-gene scene may have 'run well' with the two corresponding ribozymes promoting the replication of the circular genome from different respects. Circular genomes with more genes might have arisen later in RNA-based protocells. Therefore, circular genomes, which are common in the modern living world, may have had their 'root' at the very beginning of life.


Assuntos
RNA Catalítico , RNA Circular , RNA , RNA Circular/genética , RNA Catalítico/genética , RNA Catalítico/metabolismo , RNA/genética , RNA/metabolismo , Conformação de Ácido Nucleico , Evolução Molecular , Genoma , Simulação por Computador , Origem da Vida
4.
BMC Neurol ; 23(1): 320, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679730

RESUMO

BACKGROUND AND PURPOSE: The low-grade inflammation (LGI) score, a novel indicator of chronic LGI, combines C-reactive protein (CRP), leukocyte counts, the neutrophil/lymphocyte ratio (NLR), and the platelet (PLT) count to predict outcomes of patients with various conditions, such as cardiovascular diseases, cancers, and neurodegenerative diseases. However, few studies have examined the role of the LGI score in predicting functional outcomes of patients with ischemic stroke. The present study aimed to evaluate the association between the LGI score and functional outcomes of patients with ischemic stroke. METHODS: A total of 1,215 patients were screened in the present study, and 876 patients were finally included in this retrospective observational study based on the inclusion and exclusion criteria. Blood tests were conducted within 24 h of admission. Severity of ischemic stroke was assessed using the NIHSS score with severe stroke denoted by NIHSS > 5. Early neurological deterioration (END) was defined as an increment in the total NIHSS score of ≥ 2 points within 7 days after admission. Patient outcomes were assessed on day 90 after stroke onset using the modified Rankin Scale (mRS). RESULTS: The LGI score was positively correlated with baseline and the day 7 NIHSS scores (R2 = 0.119, p < 0.001;R2 = 0.123, p < 0.001). Multivariate regression analysis showed that the LGI score was an independent predictor of stroke severity and END. In the crude model, the LGI score in the fourth quartile was associated with a higher risk of poor outcomes on day 90 compared with the LGI score in the first quartile (OR = 5.02, 95% CI: 3.09-8.14, p for trend < 0.001). After adjusting for potential confounders, the LGI score in the fourth quartile was independently associated with poor outcomes on day 90 (OR = 2.65, 95% CI: 1.47-4.76, p for trend = 0.001). Finally, the ROC curve analysis showed an AUC of 0.682 for poor outcomes on day 90 after stroke onset. CONCLUSION: The LGI score is strongly correlated with the severity of acute ischemic stroke and that the LGI score might be a good predictor for poor outcomes on day 90 in patients with acute ischemic stroke.


Assuntos
Doenças Cardiovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Inflamação , Proteína C-Reativa
5.
BMC Neurol ; 23(1): 3, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604624

RESUMO

BACKGROUND AND PURPOSE: Mild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes. MATERIALS AND METHODS: A total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers. RESULTS: DMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors. CONCLUSION: DMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Pacientes Ambulatoriais , Disfunção Cognitiva/etiologia , Cognição , Testes Neuropsicológicos , Neuroimagem , Demência/epidemiologia
6.
Int J Neurosci ; 131(12): 1203-1208, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32546038

RESUMO

INTRODUCTION: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the severity of stroke have been reported. Systemic immune-inflammation index (SII) and platelet-albumin-bilirubin (PALBI) grade as new markers of inflammation have shown their positive association with liver cancer. The relation between SII, or PALBI and stroke remains uncertain. OBJECTIVE: To investigate the relationship between SII, PALBI grade and stroke severity. METHODS: Patients with ischemic stroke with hospital admission <24 h after symptom onset were prospectively included in a stroke registry. Demographic, clinical, and laboratory data were collected immediately after admission in all patients. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Minor stroke was defined as NIHSS score < =5, moderate-to-severe stroke as NIHSS score >5. SII, calculated as platelet × neutrophil/lymphocyte was divided into four groups according to interquartile range: lowest SII (SII < 353.9 × 109/L), low SII (353.9-532.8 × 109/L), high SII (532.8-783.9 × 109/L), and highest SII (>783.9 × 109/L) group. RESULTS: A total of 362 patients with ischemic stroke were included, and between minor and moderate-to-severe stroke significant difference was found in SII (p < 0.0001), NLR (p < 0.0001), and PLR (p = 0.001), respectively. After multivariate regression analyses, SII groups (Odd ratio = 1.351, 95% confidence interval 1.084-1.684, p = 0.007) not PALBI was an independent risk factor for stroke severity. CONCLUSION: We found that SII but not PALBI, which both are markers of inflammation, was independently associated with stroke severity.


Assuntos
Inflamação , AVC Isquêmico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Plaquetas , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Albumina Sérica
7.
J Stroke Cerebrovasc Dis ; 30(3): 105526, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33338704

RESUMO

OBJECTIVES: to investigate the relationship between insulin resistance (IR) and clinical outcomes in non-diabetic ischemic stroke patients treated with intravenous thrombolysis. METHODS: We recruited non-diabetic ischemic stroke patients treated with intravenous thrombolysis prospectively. IR was defined as homeostasis model assessment-estimated insulin resistance index ≥2.80. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI. Clinical outcomes were evaluated by neurological improvement and hemorrhagic transformation at 24 hours, and favorable functional prognosis at 90 days. RESULTS: 232 patients were enrolled into this study. IR group was 67 patients, non-IR group was 165 patients. Compared with the non-IR group, the probability of neurological improvement at 24 h ours and favorable functional outcome at 90 days in IR group were all significantly lower (41.79% vs 63.03%, p<0.01; 73.13% vs 89.09%, p<0.01 respectively), whereas the ratio of hemorrhagic transformation was much higher (16.42% vs 4.85%, p<0.01). In multivariable logistic regression, IR was negatively associated with neurological improvement and favorable functional prognosis (OR=0.39, 95%CI, 0.20-0.76, p<0.01; OR= 0.26, 95%CI, 0.07-0.91, p=0.04, respectively), but was positively correlated with hemorrhagic transformation (OR=4.07, 95%CI, 1.13-14.59, p=0.03) after adjusting traditional risk factors. We analyzed 108 infarct volume data further, the median of volume in IR group was 2.27 cm3, higher than that in non-IR group (1.96 cm3), but no statistical difference (p=0.65). CONCLUSIONS: In non-diabetic ischemic stroke patients treated with intravenous thrombolysis, IR was related with worse clinical outcomes, but not with infarct volume.


Assuntos
Fibrinolíticos/administração & dosagem , Resistência à Insulina , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , Insulina/sangue , AVC Isquêmico/diagnóstico , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
8.
Nanotechnology ; 26(50): 505703, 2015 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-26585418

RESUMO

Non-raster scanning and undersampling of atomic force microscopy (AFM) images is a technique for improving imaging rate and reducing the amount of tip-sample interaction needed to produce an image. Generation of the final image can be done using a variety of image processing techniques based on interpolation or optimization. The choice of reconstruction method has a large impact on the quality of the recovered image and the proper choice depends on the sample under study. In this work we compare interpolation through the use of inpainting algorithms with reconstruction based on optimization through the use of the basis pursuit algorithm commonly used for signal recovery in compressive sensing. Using four different sampling patterns found in non-raster AFM, namely row subsampling, spiral scanning, Lissajous scanning, and random scanning, we subsample data from existing images and compare reconstruction performance against the original image. The results illustrate that inpainting generally produces superior results when the image contains primarily low frequency content while basis pursuit is better when the images have mixed, but sparse, frequency content. Using support vector machines, we then classify images based on their frequency content and sparsity and, from this classification, develop a fast decision strategy to select a reconstruction algorithm to be used on subsampled data. The performance of the classification and decision test are demonstrated on test AFM images.

9.
Heliyon ; 10(8): e29534, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38665574

RESUMO

Objectives: This study aims to investigate whether circulating ADAMTS13 activity can offer insights into the mechanism of pathophysiological changes in deep medullary veins (DMVs). Methods: This study was conducted on a community cohort of elderly individuals in Shanghai. Plasma von Willebrand factor (VWF) levels and ADAMTS13 activity were measured. A validated DMV score described the overall burden of DMV on the brain. Through ordinal regression models, we investigated the correlation between VWF levels, ADAMTS13 activity, and increasing severity of DMV score while adjusting for demographics and cardiovascular risk factors. Results: The study enrolled 262 subjects according to the inclusion criteria. The mean VWF level (1.35 ± 0.25) was higher in the DMV group than in the group without DMV (1.25 ± 0.30) (p = 0.025), and ADAMTS13 activity (83.76 ± 7.96) was relatively lower. After adjusting for age, sex, alcohol consumption, smoking, hypertension, and diabetes, reduced ADAMTS13 activity [ß = -7.78; 95 % CI (-10.21, -5.35) p < 0.01] was associated with DMV. Moreover, correlation analysis indicated that ADAMTS13 activity was negatively correlated with the DMV score (Kendall's tau-b = -0.53, p < 0.001). Discussion: In summary, there was an inverse correlation observed between ADAMTS13 activity and the DMV score, which may provide some clinical clues for exploring the potential pathogenesis of DMV.

10.
Int J Biol Macromol ; 257(Pt 1): 128524, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38040158

RESUMO

In this study, arabinoxylans (AX) with various molecular weights (Mw) and bound ferulic acid (FA) contents were prepared to compare their effects on the gelatinization, short-term retrogradation and digestive properties of pea starch (PeS). The results indicated that all AX samples could obviously impede the pasting process of PeS and inhibit the short-term retrogradation of PeS-based gels during refrigeration by hindering the rearrangement and double helical associations of amylose. More precisely, AXs with low Mw and the highest FA content (H-FAX) exhibited the strongest intervention ability on PeS compared with the other samples. According to the Fourier transform infrared spectroscopy and X-ray diffraction results, it might be due to the unique role of bound FA as a noncovalent cross-linking agent, which enhanced the association between AX and starch molecules through extra hydrogen bonding interactions and entanglement behaviour. On these bases, H-FAX clearly improved the hardness, chewiness, moisture content, and sensory acceptance of PeS-base gels (pea jelly), and could also regulate its starch composition during short-term refrigeration to delay starch digestion. Overall, AXs with appropriate structural features might obviously improve the quality and storage stability of PeS-based foods.


Assuntos
Ácidos Cumáricos , Pisum sativum , Refrigeração , Xilanos , Amido/química , Géis/química
11.
Front Neurol ; 15: 1433010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233686

RESUMO

Background: The present study aimed to develop a reliable and straightforward Nomogram by integrating various parameters to accurately predict the likelihood of early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods: Acute ischemic stroke patients from Shaoxing People's Hospital, Shanghai Yangpu District Shidong Hospital, and Shanghai Fifth People's Hospital were recruited based on specific inclusion and exclusion criteria. The primary outcome was END. Using the LASSO logistic model, a predictive Nomogram was generated. The performance of the Nomogram was evaluated using the ROC curve, the Hosmer-Lemeshow test, and a calibration plot. Additionally, the decision curve analysis was conducted to assess the effectiveness of the Nomogram. Results: It was found that the Nomogram generated in the present study showed strong discriminatory performance in both the training and the internal validation cohorts when their ROC-AUC values were 0.715 (95% CI 0.648-0.782) and 0.725 (95% CI 0.631-0.820), respectively. Similar results were observed in two external validation cohorts when their ROC-AUC values were 0.685 (95% CI 0.541-0.829) and 0.673 (95% CI 0.545-0.800), respectively. In addition, CAD, SBP, neutrophils, TBil, and LDL were found to be positively correlated with the occurrence of END post-stroke, while lymphocytes and UA were negatively correlated. Conclusion: Our study developed a novel Nomogram that includes CAD, SBP, neutrophils, lymphocytes, TBil, UA, and LDL and it demonstrated strong discriminatory performance in identifying AIS patients who are likely to develop END.

12.
Curr Pharm Des ; 30(10): 778-785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38424424

RESUMO

BACKGROUND: Oxidized Low-Density Lipoprotein (ox-LDL) is crucial in the recrudescence and prognosis of acute ischemic stroke (AIS). We aimed to probe into the influence of cumulative ox-LDL exposure on the 90-day prognosis of AIS. METHODS: Patients with AIS were recruited in this research. AIS severity at admission was estimated with infarct volumes and National Institute of Health Stroke Scale (NIHSS) scores. AIS prognosis was assessed using Modified Rankin Scale (mRS) scores at 90 days and the change in NIHSS scores from admission to discharge. Cumulative ox-LDL exposure was defined as ox-LDL level (pg/mL) multiplied by age(y). Multivariate logistic regression analysis was employed to reveal the correlation between exposure factors and the prognosis of AIS. The prognostic prediction ability of cumulative ox-LDL exposure was compared with cumulative LDL exposure by the receiver operating characteristic curve (ROC). RESULTS: Higher cumulative ox-LDL exposure was related to worse prognosis, including neurological worsening at discharge (NIHSS increasing more than 2 points) (OR = 3.02, 95% CI, 1.30-6.98, P = 0.01) and poor functional prognosis at 90 days (mRS ≥ 3) (OR = 21.21, 95% CI, 4.72-95.36, P < 0.001). As multivariate regression analysis showed, significantly increased cumulative ox-LDL exposure was relevant to poor functional prognosis at 90 days (OR = 9.92, 95% CI, 1.23-79.76, P = 0.031), but not with neurological worsening at discharge (P = 0.414). ROC curve revealed that cumulative ox-LDL exposure had a higher predictive value (AUC = 0.843, P < 0.001) for functional prognosis of AIS than cumulative LDL exposure (AUC = 0.629, P = 0.023). CONCLUSION: Cumulative ox-LDL exposure has a positive correlation with poor prognosis at 90 days of AIS, and has a more accurate predictive ability than cumulative LDL exposure.


Assuntos
AVC Isquêmico , Lipoproteínas LDL , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/sangue , Estudos de Coortes , AVC Isquêmico/diagnóstico , AVC Isquêmico/sangue , Lipoproteínas LDL/sangue , Prognóstico , Idoso de 80 Anos ou mais
13.
Front Immunol ; 14: 1171898, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138888

RESUMO

Background and objectives: Stroke is a common group of cerebrovascular diseases that can lead to brain damage or death. Several studies have shown a close link between oral health and stroke. However, the oral microbiome profiling of ischemic stroke (IS) and its potential clinical implication are unclear. This study aimed to describe the oral microbiota composition of IS, the high risk of IS, and healthy individuals and to profile the relationship between microbiota and IS prognosis. Methods: This observational study recruited three groups: IS, high-risk IS (HRIS), and healthy control (HC) individuals. Clinical data and saliva were collected from participants. The modified Rankin scale score after 90 days was used to assess the prognosis of stroke. Extracted DNA from saliva and performed 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing. Sequence data were analyzed using QIIME2 and R packages to evaluate the association between the oral microbiome and stroke. Results: A total of 146 subjects were enrolled in this study according to the inclusion criteria. Compared with HC, HRIS and IS demonstrated a progressive increase trend in Chao1, observed species richness, and Shannon and Simpson diversity index. On the basis of permutational multivariate analysis of variance, the data indicate a great variation in the saliva microbiota composition between HC and HRIS (F = 2.40, P < 0.001), HC and IS (F = 5.07, P < 0.001), and HRIS and IS (F = 2.79, P < 0.001). The relative abundance of g_Streptococcus, g_Prevotella, g_Veillonella, g_Fusobacterium, and g_Treponema was higher in HRIS and IS compared with that in HC. Furthermore, we constructed the predictive model by differential genera to effectively distinguish patients with IS with poor 90-day prognoses from those with good (area under the curve = 79.7%; 95% CI, 64.41%-94.97%; p < 0.01). Discussion: In summary, the oral salivary microbiome of HRIS and IS subjects have a higher diversity, and the differential bacteria have some predictive value for the severity and prognosis of IS. Oral microbiota may be used as potential biomarkers in patients with IS.


Assuntos
AVC Isquêmico , Microbiota , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico , Saliva/microbiologia , Microbiota/genética , Prognóstico
14.
J Parkinsons Dis ; 13(7): 1239-1252, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37742661

RESUMO

BACKGROUND: Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA). OBJECTIVE: We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA. METHODS: This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed. RESULTS: We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (ß= 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (ß= 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients. CONCLUSIONS: Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Humanos , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Doença de Parkinson/complicações , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Cognição , Hemorragia Cerebral/complicações
16.
Comput Struct Biotechnol J ; 20: 5680-5689, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36320935

RESUMO

Recent advances in RNA engineering have enabled the development of RNA-based therapeutics for a broad spectrum of applications. Developing RNA therapeutics start with targeted RNA screening and move to the drug design and optimization. However, existing target screening tools ignore noncoding RNAs and their disease-relevant regulatory relationships. And designing therapeutic RNAs encounters high computational complexity of multi-objective optimization to overcome the immunogenicity, instability and inefficient translational production. To unlock the therapeutic potential of noncoding RNAs and enable one-stop screening and design of therapeutic RNAs, we have built the platform TREAT. It incorporates 43,087,953 regulatory relationships between coding and noncoding genes from 81 biological networks under different physiological conditions. TREAT introduces graph representation learning with Random Walk Diffusions to perform disease-relevant target screening, in addition to the commonly utilized Topological Degree and PageRank algorithms. Design and optimization of large RNAs or interfering RNAs are both available. To reduce the computational complexity of multi-objective optimization for large RNA, we stratified the features into local and global features. The local features are evaluated on the fixed-length or dynamic-length local bins, whereas the latter are inspired by AI language models of protein sequence. Then the global assessment is performed on refined candidates, thus reducing the enormous search space. Overall, TREAT is a one-stop platform for the screening and designing of therapeutic RNAs, with particular attention to noncoding RNAs and cutting-edge AI technology embedded, leading the progress of innovative therapeutics for challenging diseases. TREAT is freely accessible at https://rna.org.cn/treat.

17.
Sci Prog ; 104(3): 368504211036386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34325592

RESUMO

The current optimization research on the connectors of prefabricated barriers uses experimental comparisons only and lacks theoretically based optimization methods as guidance. The primary objective of this study was to propose an efficient optimization approach to the connector design of prefabricated bridge barriers. This paper presents an efficient two-stage optimization approach to the connector design of prefabricated bridge barriers. In the first stage, the hybrid cellular automaton algorithm is used to perform dynamic topology optimization on the connector, and the best material distribution in the design domain is obtained. In the second stage, a kriging metamodel and genetic algorithm are combined to further optimize the size of the connector structure. With a prefabricated bridge as the engineering background, finite element models of a barrier system under impact load caused by a car crash were established. The above approach is utilized to optimize the design of the barrier connector. Results showed that the optimized connector structure greatly improved the overall performance of the barrier system while reducing the material consumption and costs. The proposed optimization approach can determine the optimal material distribution and size of the connector structure, thus providing guiding significance for the design and construction of connectors of prefabricated components.

18.
Front Aging Neurosci ; 13: 738359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690744

RESUMO

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden. Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model. Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [ß = -7.31; 95% confidence interval (CI) (-9.40, -4.93); p<0.01; ß = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(ß = -9.22; 95% CI (-11.37, -7.06); p<0.01); ß = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(ß = -2.3; 95% CI (-4.95, 0.05); p = 0.22); ß = 0.02; 95% confidence interval (-0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking. Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

19.
Comput Struct Biotechnol J ; 19: 2719-2725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093987

RESUMO

Integrative analysis of multi-omics data can elucidate valuable insights into complex molecular mechanisms for various diseases. However, due to their different modalities and high dimension, utilizing and integrating different types of omics data suffers from great challenges. There is an urgent need to develop a powerful method to improve survival prediction and detect functional gene modules from multi-omics data. To deal with these problems, we present DeepOmix (a scalable and interpretable multi-Omics Deep learning framework and application in cancer survival analysis), a flexible, scalable, and interpretable method for extracting relationships between the clinical survival time and multi-omics data based on a deep learning framework. DeepOmix enables the non-linear combination of variables from different omics datasets and incorporates prior biological information defined by users (such as signaling pathways and tissue networks). Benchmark experiments demonstrate that DeepOmix outperforms the other five cutting-edge prediction methods. Besides, Lower Grade Glioma (LGG) is taken as the case study to perform the prognosis prediction and illustrate the functional module nodes which are associated with the prognostic result in the prediction model.

20.
Dis Markers ; 2021: 4998823, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950249

RESUMO

OBJECTIVE: To investigate the relationship between the decrease of plasma oxidized low-density lipoprotein (oxLDL) levels and clinical outcomes in patients with acute atherosclerosis-related ischemic stroke. METHODS: We recruited acute ischemic stroke patients within 3 days of onset consecutively. Plasma oxLDL levels were measured on the second day after admission and before discharge (10-14 days after stroke onset). Initial stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) scores, and infarct volume was measured using diffusion-weighted imaging (DWI) by the ITK-SNAP software. Clinical outcomes were evaluated by DWI volumes in the acute phase, neurological improvement at discharge, and favorable functional prognosis at 90 days. Logistic regression was performed to evaluate the association between oxLDL level decrease and clinical outcomes. RESULTS: 207 patients were enrolled in this study. Compared with the mild decrease of the oxLDL level group, patients with a significant decrease of the oxLDL level group were more likely to have a higher ratio of neurological improvement at discharge (55.07% vs. 14.49%, p < 0.01) and favorable functional prognosis at 90 days (91.30% vs. 55.07%, p < 0.01). In multivariable logistic regression, the degree of oxLDL level decrease was related to neurological improvement at discharge and favorable functional prognosis at 90 days (p < 0.01). Patients with significant decrease were more likely to have neurological improvement at discharge (OR = 7.92, 95% CI, 3.14-19.98, and p < 0.01) and favorable functional prognosis at 90 days (OR = 7.46, 95% CI, 2.40-23.23, and p < 0.01) compared to patients with mild decrease of oxLDL level. The DWI volumes in patients with different oxLDL level decrease groups had no statistical difference (p = 0.41), and the Spearman's rho between oxLDL level decrease and DWI infarct volumes was -0.03, but no statistical difference (p = 0.72). CONCLUSIONS: The degree of oxLDL level decrease is related to neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute atherosclerosis-related ischemic stroke, but not with infarct volume in the acute phase.


Assuntos
Isquemia Encefálica/sangue , Imagem de Difusão por Ressonância Magnética , AVC Isquêmico/fisiopatologia , Lipoproteínas LDL/sangue , Prognóstico , Índice de Gravidade de Doença , Idoso , Feminino , Humanos , AVC Isquêmico/sangue , Masculino , Fatores de Tempo
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