Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Equation of state of Iridium: from insight of ensemble theory.

The equations of state (EOS) of Iridium are, for the first time, obtained by solving the high-dimension integral of partition function based on a recently developed approach of ultrahigh efficiency and precision without any artificial parameter, and the deviation of 0.25% and 1.52% from the experiments was achieved respectively for the isobaric EOS in a temperature range of 300 K-2500 K and the isothermal EOS at 300 K up to 300 GPa. Specific comparisons show that the deviation of EOS based on harmonic approximation even including anharmonic effect, manifests worse than ours by several times or even one order of magnitude, indicating that ensemble theory is the very approach to understand the thermodynamic properties of condensed matter.

The effect of microorganisms on the biomodification of montan resin from lignite.

Montan resin (MR) is an industrial by-product or solid waste generated during the production of refined montan wax and is not typically reused. In this paper, a bio-modification method using three strains of microorganisms, Acinetobacter venetianus (AV), Pseudomonas aeruginosa (PA), and Phanerochaete chrysosporium (PC), was studied to promote the performance and bio-function of MR so that MR could be recycled. MR can be degraded by these three microorganisms, and their weight loss rates were similar over the treatment period of 15 days. Compared with the original MR, the hydrophilicity of modified MRs was improved, which was related to the increase in apparent oil-water partition coefficients (Kows) and oxygen-containing and hydrophilic groups in modified MRs based on IR and GC-MS analysis. The bio-function of modified MRs by the three strains in terms of promoting maize seed germination and seedling growth was greater compared with untreated MR. Overall, these findings indicate that biomodified MRs might have useful agriculture applications.Implications: An environmentally-friendly method using microorganisms to achieve recycle of solid waste, montan resin (MR) was established in this study. Through this bio-treatment, the performance and bio-function of MR were both improved, that is the appearance and hydrophilicity of modified MRs were better than thoes in before, and the modified MRs treated by three strains showed the better promoting effects on maize seed germination and seedling growth than untreated MR, indicating the modified MRs have the certain potential of agricultural utilization in the future.

Chemical modification of montan resin by peracetic acid and agricultural application of its modified products.

Montan resin (MR) is a by-product produced during the refinement process of montan wax extracted from lignite and has no usage yet. Chemical modification is an effective method to change the material property for expanding or converting the application area of the material itself. Our previous study found that the high hydrophobicity of MR is the primary limiting factor for its utilization in agriculture. Based on this point, this study attempted to chemically modify MR using the oxidation of peracetic acid, resulting that the MR hydrophilicity was significantly improved, and a water-soluble product (WSP) was obtained. The optimized oxidation conditions of MR, including the reaction temperature (X1), reaction time (X2), weight ratio of oxidant and montan resin (X3), and oxidant concentration (X4), were determined using single-factor experiments and response surface analysis. The modification degree was evaluated using elemental and oil-water partition coefficient analyses, infrared (IR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS), revealing that the oil-water partition coefficient of the modified product decreased and that the number of chemical constituents with oxygen-containing functional groups clearly increased after modification. Furthermore, the WSP was tested its effects on germination and seedling growth of the wheat seed. Compared with the control group, the WSP showed a promoting effect on the growth and germination of wheat. The WSP concentrations of 600 mg·L-1 and 300 mg·L-1 had the most substantial effect on the root and seedling growth of wheat, respectively. Implications: Montan resin, a useless by-product produced from crude montan wax, was chemically modified via oxidation of peracetic acid. Its hydrophilicity was significantly improved, and a water-soluble product was obtained after the chemical modification. The optimized oxidation conditions of montan resin were determined using single-factor experiments and response surface analysis. The amount of chemical constituents with oxygen-containing functional groups increased in the modified products after modification, as determined by IR and GC-MS analysis, among other methods. The water-soluble modified product showed an obvious effect in promoting growth and germination of wheat at 600 mg·L-1 and 300 mg·L-1, respectively.

Unstably controlled systolic blood pressure trajectories are associated with markers for kidney damage in prediabetic population: results from the INDEED cohort study.

BACKGROUND: The association between blood pressure change and kidney damage in patients with abnormal blood glucose remains unclear. The current study aimed to identify systolic blood pressure (SBP) trajectories among the prediabetic population and to determine their association with kidney damage after a long-term follow-up. METHODS: The incidence, development, and prognosis of diabetic kidney disease (INDEED) study is nested in the Kailuan cohort study with a focus on population with diabetes and prediabetes. We screened out people with prediabetes in 2006 and with more than three SBP records from 2006 to 2014 biennially. We used the latent mixture modeling to fit five groups of trajectories of SBP. In 2016, estimated glomerular filtration rate (eGFR), urinary albumin creatinine ratio (uACR), and urinary α1-microglobulin (α1MG), transferrin and α1-acid glycoprotein were measured, and the association between SBP trajectories and these markers was analyzed by linear regression and logistic regression models. RESULTS: Totally, 1451 participants with prediabetes and without kidney damage were identified in 2006. Five heterogeneous SBP trajectories were detected based on the longitudinal data from 2006 to 2014, as low-stable group (n = 323), moderate-stable group (n = 726), moderate-increasing group (n = 176), moderate-decreasing group (n = 181), and high-stable group (n = 45). Linear regression analysis showed that the moderate and high SBP groups had lower eGFR, higher uACR, higher urinary α1MG, higher transferrin, and higher α1-acid glycoprotein than the low-stable group. Multivariable analysis attenuated the association but did not change the statistical significance. CONCLUSIONS: Prediabetic patients with persistent high-level SBP trajectory or gradually increased SBP trajectory had severer kidney damage during follow-up.

[Association of drug resistance of Mycoplasma pneumoniae with DNA load and genotypes in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To investigate the association of drug resistance of Mycoplasma pneumoniae (MP) with DNA load and genotypes in children with MP pneumonia. METHODS: A total of 230 children who were hospitalized and diagnosed with MP pneumonia between January 2012 and December 2016 were enrolled. Throat swabs were collected from the 230 children, and a rapid drug sensitivity assay was used to determine the sensitivity of clinical isolates of MP to nine commonly used antibacterial agents. Quantitative real-time PCR was used to measure MP-DNA load in throat swabs. PCR sequencing was used to determine the genotype of 2063 locus of the MP 23S rRNA V domain. RESULTS: Of the 230 children, 86 (37.4%) had genotype A in 2063 locus, 134 (58.3%) had genotype G, 8 (3.5%) had genotype C, and 2 (0.9%) had genotype T. Mutant strains (genotype G+C+T) had a significantly higher MP-DNA load than wild-type strains (genotype A) (P<0.05). The strains resistant to erythromycin, azithromycin, clarithromycin, and clindamycin had a significantly higher MP-DNA load than non-resistant strains (P<0.05). MP had a high drug resistance rate to macrolide antibiotics. More than 60% of the cases with resistance to macrolides were found to have A2063G mutations. MP was rarely resistant to quinolones (less than 2%). CONCLUSIONS: Mutations in 2063 locus of the MP 23S rRNA V domain may result in the resistance of MP to macrolides and the change in DNA load and can be used as a basis for selecting drugs for MP.

[Application of Mycoplasma pneumoniae antibody and load index in the diagnosis of Mycoplasma pneumoniae pneumonia in children].

OBJECTIVE: To study the role of Mycoplasma pneumoniae (MP) load and antibody measurements in the diagnosis of MP pneumonia. METHODS: A total of 115 children with MP pneumonia and 400 healthy children were enrolled. The MP load and total antibody level were measured at different stages, and the MP load index (MPLI) was calculated. RESULTS: The cut-off value of MPLI for MP infection was 6.12. MPLI and total antibody titer increased during the course of the disease, while MP-DNA decreased rapidly. Within the same time of blood collection, the group with a higher MP load had a significantly higher total antibody titer than the group with a lower MP load (P<0.05). Within 2 weeks of the course of the disease, the negative antibody group had a significantly higher MPLI than the positive antibody group (P<0.05). CONCLUSIONS: MPLI provides a standardized quantitative value of MP-DNA and plays an important role in the early diagnosis of MP infection.

[Changes of plasma cardiotrophin-1 levels in neonates with myocardial ischemic injury].

OBJECTIVE: To study the changes and significance of plasma cardiotrophin-1 (CT-1) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury. METHODS: Forty-five neonates with HIE (15 mild cases, 24 moderate cases and 6 severe cases) were enrolled and divided into two subgroups based on the presence of myocardial injury (n=19) and not (n=26). Twenty healthy neonates were used as the control group. Plasma CT-1 levels were measured using double-antibody sandwich enzyme immunoassay method. Serum creatinine kinase MB (CK-MB) and cardiac troponin I (CTnI ) levels were also measured. RESULTS: Plasma CT-1 levels in the mild HIE (169±20 pg/mL) and moderate/severe HIE subgroups (287±44 pg/mL) were significantly higher than those in the control group (30±8 pg/mL), and plasma CT-1 levels were associated with the severity of HIE (P<0.01). Plasma CT-1 levels were positively correlated with serum CK-MB and CTnI levels in neonates with HIE in the acute phase (r=0.565 and 0.621 respectively; P<0.01). Plasma CT-1 levels in neonates with myocardial injury were significantly higher than those without myocardial injury (249 ±35 pg/mL vs 177±26 pg/mL; P<0.01). Plasma CT-1 levels were significantly reduced in neonates with myocardial injury in the convalescent phase (157±19 pg/mL) compared with those in the acute phase (249±35 pg/mL; P<0.01). CONCLUSIONS: Detection of plasma CT-1 levels may be useful in the diagnosis of myocardial ischemic injury and the severity evaluation of HIE.

[Association between CHI3L1 SNPs and susceptibility to childhood asthma].

OBJECTIVE: To investigate the association between CHI3L1 single nucleotide polymorphisms (SNPs) and the susceptibility to childhood asthma. METHODS: A total of 316 children diagnosed with asthma between January 2011 and October 2013 and 297 healthy children were selected as asthma group and control group respectively. Peripheral blood samples were collected from all subjects. Chemiluminescence and flow cytometry were applied to measure total IgE level and the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic DNA was extracted from peripheral blood hemocytes, and the genotype and allele frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by MALDI-TOP mass spectrometry. RESULTS: The total IgE and YKL-40 levels were significantly higher in the asthma group than in the control group (P<0.05), while the percentage of eosinophils showed no significant difference between the two groups (P>0.05). The frequency of GG genotype at rs883125 in the asthma group was significantly higher than that in the control group (P<0.05). For rs4950928, the asthma group had a significantly lower frequency of CC genotype (P<0.05) but a significantly higher frequency of CG genotype (P<0.05) compared with the control group. In the asthma group, the patients with GG and CG genotypes at rs4950928 had significantly increased total IgE and YKL-40 levels compared with those with CC genotype at this locus (P<0.05). CONCLUSIONS: YKL-40 is a potential molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs rs4950928 and rs883125 may be associated with childhood asthma. G allele at rs4950928 may increase the risk of childhood asthma.

Sugar uptake in the Aril of litchi fruit depends on the apoplasmic post-phloem transport and the activity of proton pumps and the putative transporter LcSUT4.

The post-phloem unloading pathway and the mechanism of sugar accumulation remain unclear in litchi fruit. A combination of electron microscopy, transport of phloem-mobile symplasmic tracer (carboxyfluorescein, CF) and biochemical and molecular assays was used to explore the post-phloem transport pathway and the mechanism of aril sugar accumulation in litchi. In the funicle, where the aril originates, abundant plasmodesmata were observed, and CF introduced from the peduncle diffused to the parenchyma cells. In addition, abundant starch and pentasaccharide were detected and the sugar concentration was positively correlated with activities of sucrose hydrolysis enzymes. These results clearly showed that the phloem unloading and post-phloem transport in the funicle were symplastic. On the other hand, imaging of CF showed that it remained confined to the parenchyma cells in funicle tissues connecting the aril. Infiltration of both an ATPase inhibitor [eosin B (EB)] and a sucrose transporter inhibitor [p-chloromercuribenzene sulfonate (PCMBS)] inhibited sugar accumulation in the aril. These results indicated an apoplasmic post-phloem sugar transport from the funicle to the aril. Although facilitated diffusion might help sucrose uptake from the cytosol to the vacuole in cultivars with high soluble invertase, membrane ATPases in the aril, especially tonoplast ATPase, are crucial for aril sugar accumulation. The expression of a putative aril vacuolar membrane sucrose transporter gene (LcSUT4) was highly correlated with the sugar accumulation in the aril of litchi. These data suggest that apoplasmic transport is critical for sugar accumulation in litchi aril and that LcSUT4 is involved in this step.

[ILs-HPLC simultanesous determination of five alkaloids in phellodenddri chinensis cortex].

A RP-HPLC method was established for simultaneous determination of phellodendrine hydrochloride (PH1), magnoflorine hydrochloride (MH), jatrorrhizine hydrochloride (JH), palmatine hydrochloride (PH2) and berberine hydrochloride (BH) in Phellodendri Chinensis Cortex by using ionic liquids as mobile phase additives. The separation was performed on a Kromasil C18 (4.6 mm x 250 mm, 5 µm) coupled with ultraviolet (UV) detection. The effect of extraction solvent, detection wavelength, length of alkyl chain on different imidazolium ionic liquids and concentration of ionic liquids on the separation and determination of alkaloids were investigated. Ionic liquid, [BMIm] BF4, can obviously improve the resolution and peak shape. This ILs-HPLC method is simple, rapid, and reliable, which can be used for determination of alkaloids in Phellodenddri Chinensis Cortex.

[Determination of protein binding rate of oleanolic acid in human plasma and serum albumin].

A LC-MS method was established for the determination of the protein binding rates of oleanolic acid in human plasma and serum albumin. The equilibrium dialysis combined with LC-MS to determine the total concentration in plasma and free drug concentration of oleanolic acid was carried out. The human plasma protein binding rates of oleanolic acid at three concentrations were 79.6%, 81.9% and 63.3%, respectively. The human serum albumin protein binding rates of oleanolic acid at three concentrations were 53.5%, 56.6% and 47.7%, respectively. The method is shown to be simple, accurate, sensitive and specific for the determination of biological samples. The protein binding rates in human plasma and serum albumin were of high strength.

Antigenic targeting of the human mannose receptor induces tumor immunity.

Pattern recognition receptors are preferentially expressed on APCs allowing selective uptake of pathogens for the initiation of antimicrobial immunity. In particular, C-type lectin receptors, including the mannose receptor (MR), facilitate APC-mediated adsorptive endocytosis of microbial glyconjugates. We have investigated the potential of antigenic targeting to the MR as a means to induce Ag-specific humoral and cellular immunity. hMR transgenic (hMR Tg) mice were generated to allow specific targeting with the anti-hMR Ab, B11. We show that hMR targeting induced both humoral and cellular antigenic specific immunity. Immunization of hMR Tg mice with B11 mAbs induced potent humoral responses independent of adjuvant. Injection of hMR Tg mice with mouse anti-hMR Ab clone 19.2 elicited anti-Id-specific humoral immunity while non-Tg mice were unresponsive. B11-OVA fusion proteins (B11-OVA) were efficiently presented to OVA-specific CD4 and CD8 T cells in MR Tg, but not in non-Tg, mice. Effector differentiation of responding T cells in MR Tg mice was significantly enhanced with concomitant immunization with the TLR agonist, CpG. Administration of both CpG and B11-OVA to hMR Tg mice induced OVA-specific tumor immunity while WT mice remained unprotected. These studies support the clinical development of immunotherapeutic approaches in cancer using pattern recognition receptor targeting systems for the selective delivery of tumor Ags to APCs.

The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma.

CD30 is a promising target for antibody-based immunotherapy of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma. To overcome the limitations from currently available murine anti-CD30 monoclonal antibodies (mAbs), a new fully human anti-CD30 antibody was generated. Binding properties were evaluated by recombinant CD30 capture enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell-sorter (FACS) flow cytometry. Activity of this new mAb was assessed in vitro using growth inhibition and antibody-dependent cellular cytotoxicity (ADCC) assays on several cell lines. In vivo activity was determined in a solid as well as in a disseminated xenografted model of HL in severe combined immunodeficiency (SCID) mice. The mAb 5F11 showed specific binding to CD30 (cluster A). The ADCC assays indicated dose-dependent lysis of L540 cells when 5F11 was combined with human effector cells. Upon cross-linking in vitro, 5F11 inhibited the growth of CD30-expressing cell lines. In vivo, treatment with 5F11 induced a marked growth delay or even a complete regression of established xenografted HL in SCID mice. In the disseminated HL model, a high proportion of 5F11-treated mice experienced long-term survival. The new human anti-CD30 monoclonal antibody 5F11 shows promise as a means of CD30-targeted immunotherapy of malignant lymphomas. Based on these results, a clinical phase 1 study in patients with refractory CD30+ lymphoma has been initiated.