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Multicomponent reactions hold the potential to maximize the synthetic efficiency in the preparation of diverse and complex molecular scaffolds. An unprecedented formal [3+1+1+1] annulation approach for the one-step synthesis of fluoroalkylated 2-H-pyrimidines commencing from perfluoroalkyl alkenes, paraformaldehyde, and ammonium carbonate is described. By harnessing readily accessible (CH2O)n and cheap (NH4)2CO3 as a formamidine surrogate, this method effectively replaces traditionally preformed amidines with a pyrimidine assembly. The multicomponent reaction proceeds in a step-economical, operationally simple, metal-free, and additive-free manner, featuring a broad substrate scope, excellent functional group compatibility, and scalability. The potential for the synthetic elaboration of the obtained 2-H-pyrimidine is further demonstrated in the alkylation and vinylation of its C2 position.
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Pretreatment is the key step to convert lignocelluloses to sustainable biofuels, biochemicals or biomaterials. In this study, a green pretreatment method based on choline chloride-lactic acid deep eutectic solvent (ChCl-LA) and niobium-based single-atom catalyst (Nb/CN) was developed for the fractionation of corn straw and further enzymatic hydrolysis of cellulose. With this strategy, significant lignin removal of 96.5 % could be achieved when corn straw was pretreated by ChCl-LA (1:2) DES over Nb/CN under 120 °C for 6 h. Enzymatic hydrolysis of the cellulose-enriched fraction (CEF) presented high glucose yield of 92.7 % and xylose yield of 67.5 %. In-depth investigations verified that the high yields of fractions and monosaccharides was attributed to the preliminary fractionation by DES and the deep fractionation by Nb/CN. Significantly, compared to other reported soluble catalysts, the synthesized single-atom catalyst displayed excellent reusability by simple filtration and enzymatic hydrolysis. The recyclability experiments showed that the combination of ChCl-LA DES and Nb/CN could be repeated at least three times for corn straw fractionation, moreover, the combination displayed remarkable feedstock adaptability.
Subject(s)
Choline , Deep Eutectic Solvents , Lactic Acid , Lignin , Niobium , Lignin/chemistry , Niobium/chemistry , Catalysis , Choline/chemistry , Hydrolysis , Deep Eutectic Solvents/chemistry , Lactic Acid/chemistry , Zea mays/chemistry , Chemical Fractionation/methodsABSTRACT
In recent years, the advancement of nanoparticle-based immunotherapy has introduced an innovative strategy for combatting diseases. Compared with other types of nanoparticles, protein nanoparticles have obtained substantial attention owing to their remarkable biocompatibility, biodegradability, ease of modification, and finely designed spatial structures. Nature provides several protein nanoparticle platforms, including viral capsids, ferritin, and albumin, which hold significant potential for disease treatment. These naturally occurring protein nanoparticles not only serve as effective drug delivery platforms but also augment antigen delivery and targeting capabilities through techniques like genetic modification and covalent conjugation. Motivated by nature's originality and driven by progress in computational methodologies, scientists have crafted numerous protein nanoparticles with intricate assembly structures, showing significant potential in the development of multivalent vaccines. Consequently, both naturally occurring and de novo designed protein nanoparticles are anticipated to enhance the effectiveness of immunotherapy. This review consolidates the advancements in protein nanoparticles for immunotherapy across diseases including cancer and other diseases like influenza, pneumonia, and hepatitis.
Subject(s)
Immunotherapy , Nanoparticles , Neoplasms , Humans , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms/therapy , Neoplasms/immunology , Proteins/chemistry , AnimalsABSTRACT
The expansion of illicit lottery activities has caused significant harm to both agricultural production and the livelihood of rural residents. An analysis of the factors that influence rural residents' participation in underground lotteries can provide crucial insight for regulating the lottery industry's development. This study examines the present state of rural residents' participation in underground lotteries, investigates the factors that impact their participation using the Double-Hurdle model, and further employs the ISM model to evaluate the correlations and hierarchical structure among the factors, using field survey data collected from 603 rural residents in S Province, China. The findings reveal that 53.07% of the respondents have participated in underground lotteries. Risk preference, information acquisition, social networks, age, education, family burden, percentage of agricultural labor, agricultural business scale, and household income significantly affect whether residents purchase lotteries (WPL). All factors, except the percentage of agricultural labor and agricultural business scale, also significantly impact underground lottery spending (LS). Among the significant influencing factors, rural residents' risk preference is the direct surface factor, whereas agricultural business scale, household income, information acquisition, and social networks are the middle indirect factors, and residents' age, education, family burden, and percentage of agricultural labor are the deep-rooted factors. It is recommended to regulate the lottery industry's development can be achieved by enhancing entertainment and cultural activities, expanding economic opportunities, enhancing rural education, increasing law awareness, and improving the public welfare lottery business model. The conclusions offer a valuable reference point for the standardized development of the lottery industry and the promotion of social stability in rural areas.
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This paper analyzes the green production efficiency (GPE) and spatial divergence of the hog breeding industry, with the aim of providing a foundation for the rational layout of hog breeding and promoting the industry's high-quality development. The paper uses the SBM model to estimate GPE in 29 provinces, cities, and districts of China from 2006 to 2019. Furthermore, it analyzes the spatial divergence of GPE and its driving factors using divergence indexes and the Geodetector. The results show that China's GPE of the hog breeding industry increased from 0.409 to 0.496 between 2006 and 2019. The highest efficiency occurred during the I-period, while the lowest efficiency was observed during the II-period. The highest efficiency was in the key development region, and the lowest efficiency was in the potential growth region. The spatial divergence of GPE in the hog breeding industry expanded, with labor input, non-point source pollution, resource endowment, and environmental load bearing being the main driving factors for the expansion in each period. The potential growth region had the largest spatial divergence, mainly affected by resource endowment. In contrast, the constrained development region had the smallest spatial divergence, mainly affected by resource endowment and pollutant emissions. The spatial divergence of moderate and key development regions was considerable, mainly affected by environmental investment, environmental load bearing, and pollutant emissions. Therefore, the key to improving the GPE of the hog breeding industry is to promote the adoption of advanced technology, such as labor-saving, material-saving, and emission reduction technologies. Moreover, several actions should be taken to reduce the spatial divergence among different regions, such as integrated breeding, clean standards, large-scale breeding, and high-end boutique.
Subject(s)
Environmental Pollutants , Financial Management , Swine , Animals , Industry , Investments , Economic Development , Efficiency , ChinaABSTRACT
OBJECTIVES: To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. METHODS: SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24 h before and 2, 4, 6, and 8 h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. RESULTS: The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2 h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). CONCLUSIONS: The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. CLINICAL RELEVANCE STATEMENT: The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. KEY POINTS: ⢠The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. ⢠Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. ⢠Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.
Subject(s)
Acute Kidney Injury , Pancreatitis , Humans , Rats , Animals , Diffusion Tensor Imaging/methods , Acute Disease , Pancreatitis/complications , Pancreatitis/diagnostic imaging , Pancreatitis/pathology , Diffusion Magnetic Resonance Imaging/methods , Kidney/pathology , Acute Kidney Injury/diagnostic imaging , Models, AnimalABSTRACT
Background: As an intestinal non-specific inflammatory lesion, ulcerative colitis (UC) affects the health of many individuals. This study examined the possible beneficial effects of the chloroform extract of Fomitopsis pinicola (Swartz.: Fr) Karst (FPKc) on UC. Methods: The mice were given free access to drink with 4% dextran sulfate sodium (DSS) for 1 week to establish acute UC model. Next, 35 mg of FPKc or sulfasalazine (SASP) was given to the mice via gavage for 3 weeks. The disease activity index (DAI) and colonic mucosa damage index (CMDI) scores were calculated. The colon tissues of the mice were collected to measure the length and perform hematoxylin and eosin staining. The thymus and spleen indexes were determined. Interleukin (IL)-6, IL-8, tumor necrosis factor-α, aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were determined. Results: FPKc or SASP treatment alleviated hematochezia and weight loss, ameliorated DAI and CMDI scores, and improved the crypt structure and length of the colon tissues. Relative to the UC model group, the spleen index in the FPKc group was reduced, which was accompanied by decreases of the IL-6 and IL-8 levels in the serum. FPKc also lowered the AST and ALT levels in the serum of the UC mice. Conclusions: FPKc protected the mice from DSS-induced UC injury. It may be that FPKc activates immune regulation and downregulates the expression of pro-inflammatory cytokines.
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The green production behavior of pig farmers is the basis for high-quality development in animal husbandry. In order to solve the problem of poor green production behaviors in small- and medium-sized pig farmers, it is necessary to analyze the influencing factors and how they interact with each other. The Rational Peasant Theory and Prospect Theory were used in this paper to analyze the occurrence motivation of the green production behaviors of small- and medium-sized pig farmers. The Logit model and the ISM analysis method were used to test the influencing factors and their mechanisms. This was conducted using data from a study of 747 small- and medium-sized pig farmers in Henan Province. The results show that the green production behaviors of small- and medium-sized pig farmers are motivated by internal expected return, affected by the monitoring pressure from external stakeholders and limited by their own resource capacity; the influencing factors of different green production behaviors are different, and there are more influencing factors of scientific disease control, standardized management and waste recycling than of rational feeding. The following shows how the influencing factors on pig farmers' green production behavior interact with one another: level of education â external pressure, farming conditions and operating characteristics â cognition of return â green production behavior (i.e., cognition of return is the direct factor; external pressure, farming conditions and operating characteristics are indirect factors; and level of education is the underlying factor). Some measures should be implemented to promote green production behaviors, such as the continuation of the support for green production, the strengthening of supervision and publicity, the increasing of investment in technology and equipment, and the improving of the green production literacy of farmers. In conclusion, this paper deepens the understanding of the mechanism of green production behaviors of small- and medium-sized pig farmers, and provides the theoretical basis and concrete measures for the government and for pig farmers.
Subject(s)
Agriculture , Farmers , Swine , Animals , Humans , Surveys and Questionnaires , Animal Husbandry/methods , Farms , ChinaABSTRACT
Background: The aim of this study was to develop a new model constructed by logistic regression for the early prediction of the severity of acute pancreatitis (AP) using magnetic resonance imaging (MRI) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system. Methods: This retrospective study included 363 patients with AP. The severity of AP was evaluated by MRI and the APACHE II scoring system, and some subgroups of AP severity were constructed based on a combination of these two scoring systems. The length of stay and occurrence of organ dysfunction were used as clinical outcome indicators and were compared across the different subgroups. We combined the MRI and APACHE II scoring system to construct the regression equations and evaluated the diagnostic efficacy of these models. Results: In the 363 patients, 144 (39.67%) had systemic inflammatory response syndrome (SIRS), 58 (15.98%) had organ failure, and 17 (4.68%) had severe AP. The AP subgroup with a high MRI score and a simultaneously high APACHE II score was more likely to develop SIRS and had a longer hospitalization. The model, which predicted the severity AP by combining extrapancreatic inflammation on magnetic resonance (EPIM) and APACHE II, was successful, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.912, which was higher than that of any single parameter. Other models that predicted SIRS complications by combining MRI parameters and APACHE II scores were also successful (all P<0.05), and these models based on EPIM and APACHE II scores were superior to other models in predicting outcome. Conclusions: The combination of MRI and clinical scoring systems to assess the severity of AP is feasible, and these models may help to develop personalized treatment and management.
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Fringe projection profilometry (FPP) is widely applied to 3D measurements, owing to its advantages of high accuracy, non-contact, and full-field scanning. Compared with most FPP systems that project visible patterns, invisible fringe patterns in the spectra of near-infrared demonstrate fewer impacts on human eyes or on scenes where bright illumination may be avoided. However, the invisible patterns, which are generated by a near-infrared laser, are usually captured with severe speckle noise, resulting in 3D reconstructions of limited quality. To cope with this issue, we propose a deep learning-based framework that can remove the effect of the speckle noise and improve the precision of the 3D reconstruction. The framework consists of two deep neural networks where one learns to produce a clean fringe pattern and the other to obtain an accurate phase from the pattern. Compared with traditional denoising methods that depend on complex physical models, the proposed learning-based method is much faster. The experimental results show that the measurement accuracy can be increased effectively by the presented method.
Subject(s)
Algorithms , Deep Learning , Humans , Imaging, Three-Dimensional/methods , Neural Networks, ComputerABSTRACT
Purpose: To study the CT characteristics of acute pancreatitis (AP) associated with preexisting fatty liver (FL) and the impact of preexisting FL on the severity of AP and persistent systemic inflammatory response syndrome (SIRS). Patients and Methods: A total of 189 patients with AP were divided into AP with and without preexisting FL. The CT features, clinical characteristics, severity of AP, and presence of persistent SIRS between the two groups were compared. Univariate and multivariate analyses were performed to determine the risk factors for predicting SIRS. The diagnostic performances of the risk factors were evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among the 189 patients, 49.7% (94/189) had preexisting FL. On CT, AP patients with preexisting FL were more likely to develop necrosis (23.4% vs 10.5%, p=0.021), local complications (45.7% vs 29.5%, p=0.025) and persistent SIRS (59.6% vs 27.4%, p<0.001). Multivariate analysis showed that preexisting FL (OR=2.863, 95% CI: 1.264-6.486, p=0.012), APACHE II≥6 (OR=1.334, 95% CI: 1.117-1.594, p=0.002), and MCTSI ≥4 (OR=1.489, 95% CI: 1.046-2.119, p=0.027) could be independent risk factors for persistent SIRS. The areas under the ROC curve of preexisting FL, APACHE II, and MCISI in diagnosing AP patients with persistent SIRS were 0.664, 0.703, and 0.783, respectively. Conclusion: Patients with preexisting FL were more likely to develop necrosis and local complications on CT and present more severe AP and persistent SIRS. Preexisting FL can be an independent risk factor in predicting the presence of persistent SIRS in patients with AP.
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Objective: To investigate the relations of serum total homocysteine (tHcy) with cerebral small vessel disease (CSVD) and cognitive function and evaluate whether CSVD mediates the effect of serum tHcy on cognitive function. Methods: A total of 1,033 consecutive eligible participants who received serum tHcy, brain magnetic resonance imaging (MRI), and neuropsychological assessment were included in this retrospective study. White matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space were evaluated based on brain MRI. We used multivariate binary logistic regression analysis, multivariate ordinal logistic regression analysis, and mediation analyses to assess the relations of serum tHcy with CSVD and cognitive function. Results: Serum tHcy levels were higher in patients with cognitive impairment than those with no cognitive impairment. Logistic regression analyses showed elevated serum tHcy was associated with cognitive impairment [odds ratio (OR): 10.475; 95% confidence interval (CI): 4.522 to 24.264; p < 0.001] and a higher CSVD burden score (OR: 17.151; 95% CI: 8.785 to 33.921; p < 0.001) after adjusting potential confounders. Compared with the lowest tHcy quartile, the multivariable-adjusted OR of the highest quartile was 4.851 (95% CI: 3.152 to 7.466; p for the trend < 0.001) for cognitive impairment, 3.862 (95% CI: 2.467 to 6.047; p for the trend < 0.001) for a severe CSVD burden score. Mediation analyses showed significant moderating effects (9.3-23.6%) by different imaging markers of CSVD on the association between higher serum tHcy levels and cognitive impairment. Conclusion: Elevated serum tHcy is associated with cognitive impairment and the development of CSVD. A proportion of the association between elevated serum tHcy and cognitive impairment may be attributed to the presence of different imaging markers of CSVD, especially the severe CSVD burden score.
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The transport and retention behavior of perfluorooctanoic acid (PFOA) in the presence of a hydrocarbon surfactant under saturated and unsaturated conditions was investigated. Miscible-displacement transport experiments were conducted at different PFOA and sodium dodecyl sulfate (SDS) input ratios to determine the impact of SDS on PFOA adsorption at solid-water and air-water interfaces. A numerical flow and transport model was employed to simulate the experiments. The PFOA breakthrough curves for unsaturated conditions exhibited greater retardation compared to those for saturated conditions in all cases, owing to air-water interfacial adsorption. The retardation factor for PFOA with a low concentration of SDS (PFOA-SDS ratio of 10:1) was similar to that for PFOA without SDS under unsaturated conditions. Conversely, retardation was greater in the presence of higher levels of SDS (1:1 and 1:10) with retardation factors increasing from 2.4 to 2.9 and 3.6 under unsaturated conditions due to enhanced adsorption at the solid-water and air-water interfaces. The low concentration of SDS had no measurable impact on PFOA air-water interfacial adsorption coefficients (Kia) determined from the transport experiments. The presence of SDS at the higher PFOA-SDS concentration ratios increased the surface activity of PFOA, with transport-determined Kia values increased by 27 and 139%, respectively. The model provided very good independently predicted simulations of the measured breakthrough curves and showed that PFOA and SDS experienced various degrees of differential transport during the experiments. These results have implications for the characterization and modeling of poly-fluoroalkyl substances (PFAS) migration potential at sites wherein PFAS and hydrocarbon surfactants co-occur.
Subject(s)
Fluorocarbons , Adsorption , Caprylates , Porosity , Surface-Active Agents , WaterABSTRACT
OBJECTIVE: As the population ages, a growing burden of cerebral small vessel disease (cSVD) has sparked extensive concerns recently. Homocysteine (Hcy), as a traditional risk factor for atherosclerosis, may also participate in the development of cSVD. By comprehensively assessing Hcy's correlation with different MRI markers of cSVD and cognitive outcomes in a homogeneous population with cSVD, this study aims to explore the value of Hcy in the clinical management of cSVD. METHODS: 231 inpatients with MRI-confirmed cSVD were enrolled in this retrospective study (mean age 66.4±10.0 years, male sex 47.6%). Along with brain MRI and plasma total Hcy (tHcy) examination, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were also performed to assess their global cognitive function. Burdens of cSVD neuroimaging features encompassing white matter hyperintensity (WMH), lacunes of presumed vascular origin, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS) were evaluated based on brain MRI demonstrations. RESULTS: After adjusting for possible confounders, statistical analyses showed that plasma tHcy levels were not only correlated with burdens of deep/periventricular WMH (P < 0.001, P for trend < 0.001; P < 0.001, P for trend < 0.001), lacunes (P < 0.001, P for trend < 0.001), lobar CMBs (P = 0.002), and EPVS in the basal ganglia (P < 0.001, P for trendâ¯=â¯0.002) but also remained an independent predictor of cognitive impairment (B=-0.159, 95%CI -0.269--0.049, Pâ¯=â¯0.005, P for trend < 0.001) in the patients with cSVD. CONCLUSIONS: Plasma tHcy levels are associated with the development of cSVD in a dose-independent manner and may predict the cognitive outcomes in cSVD patients. These findings provide a potential clue to cSVD's physiopathology and future disease management.
Subject(s)
Cerebral Small Vessel Diseases/blood , Cognition , Cognitive Dysfunction/blood , Homocysteine/blood , Leukoencephalopathies/blood , Magnetic Resonance Imaging , Mental Status and Dementia Tests , Neuroimaging , Aged , Biomarkers/blood , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/psychology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Female , Humans , Leukoencephalopathies/diagnostic imaging , Leukoencephalopathies/psychology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Registries , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
Increasing consumption of green tea is attributed to the beneficial effects of its constituents, especially polyphenols, on human health, which can be varied during leaf processing. Processing technology has the most important effect on green tea quality. This study investigated the system dynamics of eight catechins, gallic acid, and caffeine in the processing of two varieties of tea, from fresh leaves to finished tea. It was found that complex biochemical changes can occur through hydrolysis under different humidity and heating conditions during the tea processing. This process had a significant effect on catechin composition in the finished tea. The potential application of visible and near-infrared (Vis-NIR) spectroscopy for fast monitoring polyphenol and caffeine contents in tea leaves during the processing procedure has been investigated. It was found that a combination of PCA (principal component analysis) and Vis-NIR spectroscopy can successfully classify the two varieties of tea samples and the five tea processing procedures, while quantitative determination of the constituents was realized by combined regression analysis and Vis-NIR spectra. Furthermore, successive projections algorithm (SPA) was proposed to extract and optimize spectral variables that reflected the molecular characteristics of the constituents for the development of determination models. Modeling results showed that the models had good predictability and robustness based on the extracted spectral characteristics. The coefficients of determination for all calibration sets and prediction sets were higher than 0.862 and 0.834, respectively, which indicated high capability of Vis-NIR spectroscopy for the determination of the constituents during the leaf processing. Meanwhile, this analytical method could quickly monitor quality characteristics and provide feedback for real-time controlling of tea processing machines. Furthermore, the study on complex biochemical changes that occurred during the tea processing would provide a theoretical basis for improving the content of quality components and effective controlling processes.
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The objective of this research was to investigate the retention and transport behavior of GenX in five natural porous media with similar median grain diameters but different geochemical properties. Surface tensions were measured to characterize surface activity. Miscible-displacement experiments were conducted under saturated conditions to characterize the magnitude of solid-phase adsorption, while unsaturated-flow experiments were conducted to examine the impact of air-water interfacial adsorption on retention and transport. The results from surface-tension measurements showed that the impact of solution composition is greater for the ammonium form of GenX than for the acid form, due to the presence of the NH4 counterion. The breakthrough curves for the experiments conducted under saturated conditions were asymmetrical, and a solute-transport model employing a two-domain representation of nonlinear, rate-limited sorption provided reasonable simulations of the measured data. The magnitudes of solid-phase adsorption were relatively small, with the highest adsorption associated with the medium containing the greatest amount of metal oxides. The breakthrough curves for the experiments conducted under unsaturated conditions exhibited greater retardation due to the impact of adsorption at the air-water interface. The contributions of air-water interfacial adsorption to GenX retention ranged from â¼24% to â¼100%. The overall magnitudes of retardation were relatively low, with retardation factors < â¼3, indicating that GenX has significant migration potential in soil and the vadose zone. To our knowledge, the results presented herein represent the first reported data for solid-water and air-water interfacial adsorption of GenX by soil. These data should prove useful for assessing the transport and fate behavior of GenX in soil and groundwater.
Subject(s)
Groundwater , Adsorption , Physical Phenomena , Porosity , Surface TensionABSTRACT
MOTIVATION: Tumor and adjacent normal RNA samples are commonly used to screen differentially expressed genes between normal and tumor samples or among tumor subtypes. Such paired-sample design could avoid numerous confounders in differential expression (DE) analysis, but the cellular contamination of tumor samples can be an important noise and confounding factor, which can both inflate false-positive rate and deflate true-positive rate. The existing DE tools that use next-generation RNA-seq data either do not account for cellular contamination or are computationally extensive with increasingly large sample size. RESULTS: A novel linear model was proposed to avoid the problem that could arise from tumor-normal correlation for paired samples. A statistically robust and computationally very fast DE analysis procedure, contamDE-lm, was developed based on the novel model to account for cellular contamination, boosting DE analysis power through the reduction in individual residual variances using gene-wise information. The desired advantages of contamDE-lm over some state-of-the-art methods (limma and DESeq2) were evaluated through the applications to simulated data, TCGA database and Gene Expression Omnibus (GEO) database. AVAILABILITY AND IMPLEMENTATION: The proposed method contamDE-lm was implemented in an updated R package contamDE (version 2.0), which is freely available at https://github.com/zhanghfd/contamDE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Neoplasms , RNA-Seq , Humans , Linear Models , Neoplasms/genetics , Sequence Analysis, RNA , SoftwareABSTRACT
BACKGROUND: Computed tomography (CT) or MR images may cause the severity of early acute pancreatitis (AP) to be underestimated. As an innovative image analysis method, radiomics may have potential clinical value in early prediction of AP severity. PURPOSE: To develop a contrast-enhanced (CE) MRI-based radiomics model for the early prediction of AP severity. STUDY TYPE: Retrospective. SUBJECTS: A total of 259 early AP patients were divided into two cohorts, a training cohort (99 nonsevere, 81 severe), and a validation cohort (43 nonsevere, 36 severe). FIELD STRENGTH/SEQUENCE: 3.0T, T1 -weighted CE-MRI. ASSESSMENT: Radiomics features were extracted from the portal venous-phase images. The "Boruta" algorithm was used for feature selection and a support vector machine model was established with optimal features. The MR severity index (MRSI), the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the bedside index for severity in acute pancreatitis (BISAP) were calculated to predict the severity of AP. STATISTICAL TESTS: Independent t-test, Mann-Whitney U-test, chi-square test, Fisher's exact tests, Boruta algorithm, receiver operating characteristic analysis, DeLong test. RESULTS: Eleven potential features were chosen to develop the radiomics model. In the training cohort, the area under the curve (AUC) of the radiomics model, APACHE II, BISAP, and MRSI were 0.917, 0.750, 0.744, and 0.749, and the P value of AUC comparisons between the radiomics model and scoring systems were all less than 0.001. In the validation cohort, the AUC of the radiomics model, APACHE II, BISAP, and MRSI were 0.848, 0.725, 0.708, and 0.719, respectively, and the P value of AUC comparisons were 0.96 (radiomics vs. APACHE II), 0.40 (radiomics vs. BISAP), and 0.46 (radiomics vs. MRSI). DATA CONCLUSION: The radiomics model had good performance in the early prediction of AP severity. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:397-406.
Subject(s)
Pancreatitis , Acute Disease , Humans , Magnetic Resonance Imaging , Pancreatitis/diagnostic imaging , Predictive Value of Tests , Retrospective StudiesABSTRACT
BACKGROUND: Cognitive impairment, including mild cognitive impairment and its progressive deterioration to dementia, results in great hazards to the patient and the surrounding society. While some of the risk factors are unmodifiable, such as age, lower educational attainment, and genetic factors, another proposed one-homocysteine, an amino acid produced in the methylation cycle of protein metabolism is modifiable by cheap and easily accessible B-vitamins treatments in medical practice. OBJECTIVE AND METHODS: To investigate the relationship between homocysteine and cognitive impairment, elucidate the underlying pathophysiological mechanisms and exploit any potential therapeutic values of homocysteine-lowering treatments in prevention and/or treatment in cognitive decline, we searched on the PUBMED databases surrounding around the physiological homocysteine metabolism, detrimental effects of abnormal homocysteine concentrations on the brain, and review observational and interventional experiments to date estimating the relationship between homocysteine and cognitive impairment with relatively powerful evidence. RESULTS: Intrinsic and environmental factors help maintain the normal homocysteine concentrations, and pathological homocysteine concentrations exert adverse effects mediated by cellular and vascular pathways. Although many observational studies have suggested a causal link between hyperhomocysteinemia and cognitive impairment, the majority of randomized controlled trials failed to observe marked benefits on cognition by homocysteine-lowering treatments using B-vitamins, partly arising from some design limitations including: not identifying individuals at earlier stages of cognitive impairment who are most likely to benefit, overlooking any latent safety hazards of multiple vitamin supplementation, lack of sensitive and domain-specific cognitive tests, and interference of other underappreciated factors. CONCLUSION: More studies are required to better explain the related pathophysiological mechanisms, improve experimental methods, and investigate the preventive or/and therapeutic effects of homocysteine-lowering strategies on cognitive impairment.