Opening the black box: interpretable machine learning for predictor finding of metabolic syndrome.

OBJECTIVE: The internal workings ofmachine learning algorithms are complex and considered as low-interpretation "black box" models, making it difficult for domain experts to understand and trust these complex models. The study uses metabolic syndrome (MetS) as the entry point to analyze and evaluate the application value of model interpretability methods in dealing with difficult interpretation of predictive models. METHODS: The study collects data from a chain of health examination institution in Urumqi from 2017 ~ 2019, and performs 39,134 remaining data after preprocessing such as deletion and filling. RFE is used for feature selection to reduce redundancy; MetS risk prediction models (logistic, random forest, XGBoost) are built based on a feature subset, and accuracy, sensitivity, specificity, Youden index, and AUROC value are used to evaluate the model classification performance; post-hoc model-agnostic interpretation methods (variable importance, LIME) are used to interpret the results of the predictive model. RESULTS: Eighteen physical examination indicators are screened out by RFE, which can effectively solve the problem of physical examination data redundancy. Random forest and XGBoost models have higher accuracy, sensitivity, specificity, Youden index, and AUROC values compared with logistic regression. XGBoost models have higher sensitivity, Youden index, and AUROC values compared with random forest. The study uses variable importance, LIME and PDP for global and local interpretation of the optimal MetS risk prediction model (XGBoost), and different interpretation methods have different insights into the interpretation of model results, which are more flexible in model selection and can visualize the process and reasons for the model to make decisions. The interpretable risk prediction model in this study can help to identify risk factors associated with MetS, and the results showed that in addition to the traditional risk factors such as overweight and obesity, hyperglycemia, hypertension, and dyslipidemia, MetS was also associated with other factors, including age, creatinine, uric acid, and alkaline phosphatase. CONCLUSION: The model interpretability methods are applied to the black box model, which can not only realize the flexibility of model application, but also make up for the uninterpretable defects of the model. Model interpretability methods can be used as a novel means of identifying variables that are more likely to be good predictors.

Construction of Xinjiang metabolic syndrome risk prediction model based on interpretable models.

BACKGROUND: We aimed to construct simple and practical metabolic syndrome (MetS) risk prediction models based on the data of inhabitants of Urumqi and to provide a methodological reference for the prevention and control of MetS. METHODS: This is a cross-sectional study conducted in the Xinjiang Uygur Autonomous Region of China. We collected data from inhabitants of Urumqi from 2018 to 2019, including demographic characteristics, anthropometric indicators, living habits and family history. Resampling technology was used to preprocess the data imbalance problems, and then MetS risk prediction models were constructed based on logistic regression (LR) and decision tree (DT). In addition, nomograms and tree diagrams of DT were used to explain and visualize the model. RESULTS: Of the 25,542 participants included in the study, 3,267 (12.8%) were diagnosed with MetS, and 22,275 (87.2%) were diagnosed with non-MetS. Both the LR and DT models based on the random undersampling dataset had good AUROC values (0.846 and 0.913, respectively). The accuracy, sensitivity, specificity, and AUROC values of the DT model were higher than those of the LR model. Based on a random undersampling dataset, the LR model showed that exercises such as walking (OR=0.769) and running (OR= 0.736) were protective factors against MetS. Age 60 ~ 74 years (OR=1.388), previous diabetes (OR=8.902), previous hypertension (OR=2.830), fatty liver (OR=3.306), smoking (OR=1.541), high systolic blood pressure (OR=1.044), and high diastolic blood pressure (OR=1.072) were risk factors for MetS; the DT model had 7 depth layers and 18 leaves, with BMI as the root node of the DT being the most important factor affecting MetS, and the other variables in descending order of importance: SBP, previous diabetes, previous hypertension, DBP, fatty liver, smoking, and exercise. CONCLUSIONS: Both DT and LR MetS risk prediction models have good prediction performance and their respective characteristics. Combining these two methods to construct an interpretable risk prediction model of MetS can provide methodological references for the prevention and control of MetS.

Hybrid of Resveratrol and Glucosamine: An Approach To Enhance Antioxidant Effect against DNA Oxidation.

Resveratrol exhibits various pharmacological activities, which are dependent upon phenolic hydroxyl groups. In this work, glucosamine, lipoic acid, or adamantanamine moiety was applied for attaching to ortho-position of hydroxyl group in resorcinol moiety of resveratrol (known as position-2). Antioxidant effects of the obtained hybrids were characterized using DNA oxidative systems mediated by •OH, Cu2+/glutathione (GSH), and 2,2'-azobis(2-amidinopropanehydrochloride) (AAPH), respectively. The glucosyl-appended imine and amine at position-2 of resveratrol were found to show higher inhibitory effects than other resveratrol derivatives against AAPH-induced DNA oxidation. The antioxidative effect was quantitatively expressed by stoichiometric factor ( n, the number of radical-propagation terminated by one molecule of antioxidant). The stoichiometric factors of glucosyl-appended imine and amine of resveratrol increased to 4.74 (for imine) and 4.97 (for amine), respectively, higher than that of resveratrol (3.70) and glucoside of resveratrol (3.49). It was thereby concluded that the combination of resveratrol with glucosamine at position-2 represented a novel pathway for modifying resveratrol structure in the protection of DNA against peroxyl radical-mediated oxidation.

Macroscopic and microscopic analysis of the effects of moisture content and dry density on the strength of loess.

To clarify the impact of moisture content and dry density on the strength of loess, the remolded loess samples with different moisture content and dry density were prepared, and the influence of moisture content and dry density on loess strength was explored from the macro level by direct shear test without suction control. On this basis, the mechanism of the influence of moisture content and dry density on loess strength was explored from the micro level by nuclear magnetic resonance method. The research results indicate that: In the case of low water content, there are peak points in the stress-strain curve of remolded loess, exhibiting strain softening characteristics. In the case of high water content, there is no obvious peak in the stress-strain curve, exhibiting strain hardening characteristics. Moisture has a significant impact on the shear strength of remolded loess. As the moisture content of the soil sample increases, the cohesion decreases significantly, and the change in internal friction angle is not obvious. As the moisture content continues to increase, the free water content continues to increase. Free water will continuously soften the soil particle structure, reduce the bonding force between soil particles, and cause the cohesion to decrease with the increase of moisture content. The change in dry density also has a significant impact on the shear strength parameters of remolded loess. As the dry density of the soil sample increases, the cohesion increases. The smaller the dry density, the larger the pore ratio, and the looser the contact between soil particles, weakening the bonding effect. The larger the pore ratio, the more bound water is converted to free water, and the strong bonding force between the water film and soil particles disappears. Both of these microscopic factors can lead to a decrease in cohesion with a decrease in dry density.

Tunnel construction in shallow soft rock using the pipe shed support.

In order to clarify the impact mechanism of shallow buried soft rock tunnel excavation on the upper existing highway, as well as the mechanism of pipe shed reinforcement, a combination of theoretical analysis and on-site monitoring was used to conduct in-depth research on the Diantou Tunnel Crossing the existing highway project of Dayong Expressway. The impact of shallow buried soft rock tunnel crossing construction on the existing highway and safety control issues were studied, a new deformation control index, namely deformation difference rate, was introduced. The results show that the main lateral area of influence of rock deformation is within a distance of one diameter, and the overall area of influence is within a distance of twice the diameter. From the perspective of axial tunnel deformation, the deformation of surrounding rock tends to be stable when the excavation face passes through the monitoring section about twice the tunnel diameter. Effectively controlling rock deformation depends on the total amount of settlement deformation, the change rate of deformation, and the difference rate of deformation. For V-class shallow buried tunnel surrounding rock, in order to prevent cracks on the surface, the cumulative deformation of the surrounding rock needs to be less than 50 mm, the change rate needs to be less than 3 mm/day, and the difference rate needs to be less than 5 mm/m. Finally, the proposed control standard for surface subsidence is given for similar engineering reference.

Causal association study of the dynamic development of the metabolic syndrome based on longitudinal data.

The dynamic progression of metabolic syndrome (MetS) includes developmental deterioration and reverse recovery; however, the key factors in this bidirectional progression have not been identified. Our study aimed to use the data obtained from the China Health and Retirement Longitudinal Study (CHARLS) and construct a Bayesian network to explore the causal relationship between influential factor and the development and recovery of MetS. Followed up at 4 years, forward progression of MetS occurred in 1543 and reverse recovery of MetS occurred in 1319 of 5581 subjects. Bayesian Networks showed that hyperuricemia and body mass index (BMI) levels directly influenced progression of MetS, and gender, exercise and age play an indirect role through hyperuricemia and BMI levels; high hemoglobin A1c (HbA1c) and BMI levels directly influenced recovery of MetS, and gender and exercise play an indirect role through BMI levels. Bayesian Network inference found that the rate of progression of MetS in subjects with hyperuricemia increases from 36 to 60%, the rate of progression of MetS in subjects with overweight or obese increases from 36 to 41% and the rate of reverse recovery rate of MetS in subjects with high HbA1c decreased from 33 to 20%. Therefore, attention to individuals at high risk of hyperuricemia, high HbA1c levels, and overweight/obesity should be enhanced, with early detection and following healthy behavioral interventions to prevent, control and delay the progression of MetS and its components.

Corrigendum: Active substances of myxobacteria against plant diseases and their action mechanisms.

[This corrects the article DOI: 10.3389/fmicb.2023.1294854.].

Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles as inhibitors of transforming growth factor-ß type I receptor (ALK5).

A series of 2-(6-methylpyridin-2-yl)-1H-imidazoles were synthesized and evaluated for ALK5 inhibitory activity in cell-based luciferase reporter assays. The compound 4-(((1-(benzo[d][1,3]dioxol-5-yl)-2-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)methyl)amino)benzenesulfonamide (27a) exhibited slightly higher inhibition (IC50=0.24µM) than SB431542 (IC50=0.35µM), a well known potent ALK5 inhibitor. The binding mode of 27a generated by flexible docking study shows that it fits well into the site cavity of ALK5 by forming several tight interactions.

Study on Quench Sensitivity during Isothermal Treatment of 7A65 Aluminum Alloy.

The quenching sensitivity of 7A65 aluminum alloy was investigated using interrupted quenching experiments. The time-temperature transformation (TTT) and time-temperature performance (TTP) curves of the alloy were determined. The results indicate that the nose temperature is about 320 °C and the quenching sensitivity temperature range is from 240 °C to 360 °C. During the isothermal treatment, the supersaturated solid solution resolves to the equilibrium phase of η (MgZn2), and the precipitation rate is the largest at about 320 °C. Through transmission electron microscope (TEM) observation and X-ray diffraction (XRD) tests, it was found that with the extension of the isothermal holding time, the originally dispersed η' phase gradually decreases until disappear, and the number of η phase increases and gradually grows up at the grain boundary or around the Al3Zr particles. The rod-like η phase at the grain boundary is distributed from discontinuous distribution to chain-like continuous distribution, and the precipitation free zone (PFZ) is gradually generated and widened as the holding time is extended. At the nose temperature, the driving force of nucleation is high, and the diffusion rate is fast, which promotes the precipitation and growth of η phases. The coarse η phase weakens the mechanical properties. According to the results, it is recommended to increase the cooling rate at the sensitivity temperature range to reduce the precipitation of the η phase and decrease the quenching cooling rate from solution temperature to 360 °C to reduce residual stresses in the components.

Chitooligosaccharide-induced plant stress resistance.

In nature, the production of plant stress resistance traits is often induced by extreme environmental conditions. Under extreme conditions, plants can be irreversibly damaged. Intervention with phytostimulants, however, can improve plant stress resistance without causing damage to the plants themselves, hence maintaining the production. For example, exogenous substances such as proteins and polysaccharides can be used effectively as phytostimulants. Chitooligosaccharide, a plant stimulant, can promote seed germination and plant growth and development, and improve plant photosynthesis. In this review, we summarize progress in the research of chitooligosaccharide-induced plant stress resistance. The mechanism and related experiments of chitooligosaccharide-induced resistance to pathogen, drought, low-temperature, saline-alkali, and other stresses are classified and discussed. In addition, we put forward the challenges confronted by chitooligosaccharide-induced plant stress resistance and the future research concept that requires multidisciplinary cooperation, which could provide data for the in-depth study of the effect of chitooligosaccharide on plants.

Active substances of myxobacteria against plant diseases and their action mechanisms.

Myxobacteria have a complex life cycle and unique social behavior, and obtain nutrients by preying on bacteria and fungi in soil. Chitinase, ß-1,3 glucanase and ß-1,6 glucanase produced by myxobacteria can degrade the glycosidic bond of cell wall of some plant pathogenic fungi, resulting in a perforated structure in the cell wall. In addition, isooctanol produced by myxobacteria can lead to the accumulation of intracellular reactive oxygen species in some pathogenic fungi and induce cell apoptosis. Myxobacteria can also perforate the cell wall of some plant pathogenic oomycetes by ß-1,3 glucanase, reduce the content of intracellular soluble protein and protective enzyme activity, affect the permeability of oomycete cell membrane, and aggravate the oxidative damage of pathogen cells. Small molecule compounds such as diisobutyl phthalate and myxovirescin produced by myxobacteria can inhibit the formation of biofilm and lipoprotein of bacteria, and cystobactamids can inhibit the activity of DNA gyrase, thus changing the permeability of bacterial cell membrane. Myxobacteria, as a new natural compound resource bank, can control plant pathogenic fungi, oomycetes and bacteria by producing carbohydrate active enzymes and small molecular compounds, so it has great potential in plant disease control.

The preparation and antioxidant activities of four 2-aminoacyl-chitooligosaccharides.

Chitooligosaccharides (COS) with two different molecular weights are acylated with four nonpolar amino acids: glycine (Gly), alanine (Ala), valine (Val) and leucine (Leu) to obtain 2-aminoacetyl-chitooligosaccharide (2-GlyCOS), 2-aminopropionyl-chitooligosaccharide (2-AlaCOS), 2-amino-3-methylbutyryl-chitooligosaccharide (2-ValCOS), and 2-amino-4-methylpentanoyl-chitooligosaccharide (2-LeuCOS). The structure of the derivatives was characterized by FT-IR spectroscopy, 13C NMR spectroscopy, and elemental analysis. The antioxidant activities of the derivatives, such as hydroxyl radical (·OH) scavenging ability, superoxide anion (O2·-) scavenging ability, reducing ability, and DPPH radical scavenging ability, were investigated using various established systems. Compared with chitooligosaccharide and nonpolar amino acids, all derivatives have strong scavenging ability toward hydroxyl radicals and superoxide anions, and the clearance rate was 19.05% and 67.70% separately. The reducing ability and DPPH free radical scavenging ability of the derivatives are only 0.021Abs and 32.97%. Among them, only 2-AlaLCOS has significant reducing ability, and the value can reach 0.143Abs. The above results showed that the antioxidant activity of some derivatives was higher than that of chitooligosaccharide. The water solubility of the new derivatives was also greatly improved compared to that of nonpolar amino acids. Therefore, the application of 2-aminoacyl-chitooligosaccharides (2-AACOS) in antioxidants has laid a foundation and has certain potential application value in the fields of medicine, agriculture, and animal husbandry.

The preparation and antioxidant activities of three phenyl-acylchitooligosaccharides.

Chitooligosaccharides with two different molecular weights are acylated with three containing benzene carboxylic acids: salicylic acid (BHA), α-naphthylacetic acid (NAA) and indole-3-butyric acid (IBA) to obtain o-hydroxybenzoyl-chitooligosaccharide, α-naphthylacetyl-chitooligosaccharide, and 3-Indolebutyryl-chitooligosaccharide. The structure of the derivatives was characterized by FT-IR spectroscopy, 13C NMR spectroscopy and elemental analysis. According to several amide characteristic absorption peaks between 1750 cm-1-1500 cm-1 in the FT-IR spectrum, it can be determined that the target group has been successfully grafted. And there are obvious characteristic absorption peaks of aromatic ring at 900-650 cm-1. The six chemical shifts of 98.02, 76.42, 74.83, 72.00, 60.39, 55.37 ppm in 13C NMR proved that the chitooligosaccharide did not destroy its own sugar ring structure during the reaction. The antioxidant activities of the derivatives, such as hydroxyl radical (·OH) scavenging ability, superoxide anion (O2·-) scavenging ability, reducing ability, and DPPH radical scavenging ability were investigated using various established systems. Comparing with chitooligosaccharide and containing benzene carboxylic acids, most derivatives have strong scavenging ability toward superoxide anions and DPPH radicals, and the clearance rate up to 47.44% and 80.27% separately. The reducing ability and hydroxyl free radical scavenging ability of the derivatives are only 0.032 Abs and 11.43%. The above results showed that the antioxidant activity of some derivatives was higher than that of chitooligosaccharide. The water solubility of the new derivatives was also greatly improved than that of containing benzene carboxylic acids. Therefore, the application of phenyl-acyl-chitooligosaccharide in antioxidants has laid a foundation, and has certain potential application value in the fields of medicine and agriculture and animal husbandry.

Relationship between vitamin D receptor gene polymorphisms and second acid-fast bacilli smear-positive during treatment for tuberculosis patients.

PURPOSE: Tuberculosis (TB) treatment is associated with Vitamin D. This study aimed to explore the relationship between Vitamin D receptor (VDR) gene polymorphisms and second acid-fast bacilli (AFB) smear-positive during treatment for TB patients. METHODS: This was a cross-sectional study. Seven hundred and thirty-one TB patients whose single nucleotide polymorphism site (SNPs) of VDR gene were detected from December 2019 to December 2020 in XinJiang of China. The genotypic distributions in each group were tested separately for Hardy-Weinberg equilibrium. The tetragram test was used to construct haplotypes to evaluate the association between each haplotype and second AFB smear-positive occurrence. RESULTS: No significant deviations were observed with all the four polymorphism sites in the genotypic distributions (P>0.05). Linkage disequilibrium (LD) analysis showed that there was LD between SNPs of VDR gene (r2=0.74, D`>0.9). Each haplotype was not considered to be the influencing factor of second AFB smear-positive. CONCLUSIONS: There is no association between VDR gene polymorphism (ApaI, BsmI, FokI and TaqI) and second AFB smear-positive.

The relationship between vitamin D level and second acid-fast bacilli (AFB) smear-positive during treatment for TB patients was inferred by Bayesian network.

BACKGROUND: Vitamin D is related to human immunity, so we used Bayesian network model to analyze and infer the relationship between vitamin D level and the acid-fast bacilli (AFB) smear-positive after two months treatment among pulmonary tuberculosis (TB) patients. METHODS: This is a cross-sectional study. 731 TB patients whose vitamin D level were detected and medical records were collected from December 2019 to December 2020 in XinJiang of China. Logistic regression was used to analyze the influencing factors of second AFB smear-positive. Bayesian network was used to further analyze the causal relationship among vitamin D level and the second AFB smear-positive. RESULTS: Baseline AFB smear-positive (OR = 6.481, 95%CI: 1.604~26.184), combined cavity (OR = 3.204, 95%CI: 1.586~6.472), full supervision (OR = 8.173, 95%CI:1.536~43.492) and full management (OR = 6.231, 95%CI:1.031~37.636) were not only the risk factors and can also be considered as the reasons for second AFB smear-positive in TB patients (Ensemnle > 0.5). There was no causal relationship between vitamin D level and second AFB smear-positive (Ensemnle = 0.0709). CONCLUSIONS: The risk factors of second AFB smear-positive were baseline AFB smear-positive, combined cavity, full supervision and full management. The vitamin D level in TB patients was not considered as one of the reasons for the AFB smear-positive.

Cp*RhIII-Catalyzed Sulfonamide-Directed Ortho Arene C-H Carbenoid Functionalization with Pyridotriazoles.

In this Letter, triazoles as carbene reagents were used for sulfonamide-directed C-H insertion carbenoid functionalization to construct benzylpyridine sulfonamide dual-pharmacophore compounds. This method is simple and efficient and can be used for the late-stage modification of sulfonamide drugs.

Experimental study of land subsidence in response to groundwater withdrawal and recharge in Changping District of Beijing.

Over exploitation of groundwater in Changping District of Beijing city has caused serious land subsidence in the past decades. In recent years, the operation of the South-to-North Water Transfer Project has reduced the land subsidence rate. In this paper, Experimental tests are performed using the GDS Consolidation Testing System to characterize the compression and rebound of soils at depths of less than 100 m caused by groundwater withdrawal and recharge in Changping District. The results indicate that the compressible layers are the main contributors to land subsidence. The first compressible layer experiences greater deformation and more considerable hysteresis than the other compressible layers with the same decrease in the pore water pressure. Therefore, the exploitation of the adjacent aquifer should be controlled in the future. The deformation in the second and third compressible layers is a gradual and long-term process with little rebound; therefore, the subsidence should be seriously addressed when the groundwater in the two compressible layers is exploited on a large scale. In the same compressible layer, silty clay is more compressible and hysteretic than silt. For the same soil sample, the deformation rate decreases gradually as the pore water pressure decreases, whereas the creep deformation shows an overall increasing trend. A parameter named the subsidence index Cw is proposed in this paper to describe the soil compressibility during groundwater withdrawal. All the soil samples are characterized by elastic-plastic deformation, and the shallow soil samples with less pore water pressure decrease are more likely to rebound.

Tetrahydropyrrolization of Resveratrol and Other Stilbenes Improves Inhibitory Effects on DNA Oxidation.

The inhibitory effect of resveratrol on DNA oxidation caused by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) was found to be enhanced if the C=C bond in resveratrol was converted into tetrahydropyrrole by reaction with azomethine ylide (CH2 =N(+) (CH3 )CH2 (-) ). This encouraged us to explore whether the inhibitory activities of other stilbenes could also be increased by the same method. We found that the inhibitory effects of the tetrahydropyrrole derivatives on AAPH-induced oxidation of DNA were higher than those of the corresponding stilbenes, because the tetrahydropyrrole motif can provide hydrogen atoms to be abstracted by radicals. Therefore, the tetrahydropyrrolization offered an advantage for enhancing the antioxidant effects of stilbenes. Notably, (CH3 )3 SiCH2 N(CH3 )CH2 OCH3 (in the presence of CF3 COOH) and (CH3 )3 NO (in the presence of LiN(iPr)2 ) can be used to generate azomethine ylide for the tetrahydropyrrolization of stilbenes containing electron-withdrawing and -donating groups, respectively.