Application Value of Magnetic Resonance Radiomics and Clinical Nomograms in Evaluating the Sensitivity of Neoadjuvant Chemotherapy for Nasopharyngeal Carcinoma.

OBJECTIVE: To predict the sensitivity of nasopharyngeal carcinoma (NPC) to neoadjuvant chemotherapy (NACT) based on magnetic resonance (MR) radiomics and clinical nomograms prior to NACT. MATERIALS AND METHODS: From January 2014 to July 2015, 284 consecutive patients with pathologically confirmed NPC underwent 3.0 T MR imaging (MRI) before initiating NACT. The patients' data were randomly assigned to a training set (n = 200) or a test set (n = 84) at a ratio of 7:3. The clinical data included sex, tumor (T) stage, lymph node (N) stage, American Joint Committee on Cancer (AJCC) stage, and the plasma concentration of Epstein-Barr virus (EBV) DNA. The regions of interest (ROI) were manually segmented on the axial T2-weighted imaging (T2WI) and enhanced T1-weighted imaging (T1WI) sequences using ITK-SNAP software. The radiomics data were post-processed using AK software. Moreover, the Maximum Relevance Minimum Redundancy (mRMR) algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for dimensionality reduction to screen for the features that best predicted the treatment efficacy, and clinical risk factors were used in combination with radiomics scores (Rad-scores) to construct the clinical radiomics-based nomogram. DeLong's test was utilized to compare the area under the curve (AUC) values of the clinical radiomics-based nomogram, radiomics model, and clinical nomogram. Decision curve analysis (DCA) was employed to evaluate each model's net benefit. RESULTS: The clinical nomogram was constructed based on data from patients who were randomly assigned according to T2WI and enhanced T1WI sequences. In the training set, the T2WI sequence-based clinical radiomics nomogram and the radiomics model outperformed the clinical nomogram in predicting the NACT efficacy (AUC, 0.81 vs. 0.60, p = 0.001279 and 0.76 vs. 0.60, p = 0.03026). These findings were well-verified in the test set. The enhanced T1WI sequence-based clinical radiomics nomogram exhibited better performance in predicting treatment efficacy than the clinical nomogram (AUC, 0.79 vs. 0.62, respectively; p = 0.0000834). The DCA revealed that the T2WI and clinical radiomics-based nomograms resulted in a net benefit in predicting the NACT efficacy. CONCLUSION: The clinical radiomics-based nomogram improved the prediction of NACT efficacy, with the T2WI sequence-based clinical radiomics achieving the best effect.

Process steps for the fractionation of immunoglobulin (Ig) G depleted of IgA, isoagglutinins, and devoid of in vitro thrombogenicity.

BACKGROUND: Plasma-derived immunoglobulins (IgG) are essential medicines that are in worldwide shortage, especially in low- and middle-income countries. Optimised manufacturing processes can increase supply. We evaluated various new process steps for IgG fractionation. MATERIAL AND METHODS: A crude, worst-case, IgG intermediate obtained by caprylic acid fractionation of cryoprecipitate-poor plasma was used as starting experimental material. It was processed inline by Fractogel® (Merck) TMAE anion-exchanger to deplete IgA and IgM, Eshmuno® P (Merck) anti-A and anti-B affinity chromatography to remove anti-A and anti-B isoagglutinins, 0.3% TnBP-1% Triton X-100 (S/D) treatment, C18 chromatography for removal of S/D agents, and single-pass tangential flow filtration (SPTFF) concentration to 20%. Quality, safety, and recovery were evaluated at small and pilot scales to assess purity, removal of IgA, IgM isoagglutinins, S/D agents, thrombogenic factors, and lack of toxicity in a cell model. RESULTS: The starting IgG intermediate contained approximately 90% IgG, IgA, and IgM and 10% albumin. Fractogel® TMAE, equilibrated in 25 mM sodium acetate-pH 6.0 and loaded with up to 225 mg of IgG/mL, could remove IgA and IgM, with over 94% IgG recovery with preserved sub-class distribution in the flow-through. Sequential Eshmuno®-P anti-A and anti-B columns efficiently removed isoagglutinins. The C18 packing, used at up to 17 mL of S/D-IgG solution per mL, removed TnBP and Triton X-100 to less than 1 and 2 ppm, respectively. The 20% purified IgG was devoid of activated factor XI and thrombin generation activity. DISCUSSION: This purification sequence yields a >99% pure, 20% (v/v) IgG product, depleted of IgA, isoagglutinins, and thrombogenic markers, and should be implementable on various IgG intermediates to help improve the supply of immunoglobulins.

[Construction of integrative vector for xylulokinase gene and its overexpression in Saccharomyces cerevisiae].

OBJECTIVE: An integrative vector of Saccharomyces cerevisiae for xylulokinase gene expression was constructed to overexpress xylulokinase activity. METHODS: On the basis of plasmid p406ADH1, 4 components were integrated, which were KanR gene as G418 resistant marker, ADH1 terminator fragment, xylulokinase gene from Saccharomyces cerevisiae W5 and 18S rDNA sequence for homologous recombination. After enzyme digestion and ligation, high copy recombinant expression vector pCXS-RKTr was constructed. pCXS-RKTr was linearized and transferred into Saccharomyces cerevisiae W5 , then xylulokinase activity was detected to determine the expression of pCXS-RKTr. RESULTS: Xylulokinase gene located on pCXS-RKTr was highly expressed in W5. The xylulokinase activity was 2. 87 times of the original strain. CONCLUSION: An integrative vector of industry strain Saccharomyces cerevisiae is successfully constructed and xylulokinase gene of Saccharomyces cerevisiae itself was over expressed by this vector. This intergrative vector can efficiently raise the xylulokinase activity of Saccharomyces cerevisiae. This system laid a foundation for the construction of gene engineering Saccharomyces cerevisiae strain which can ferment xylose to ethanol.