We confirmed the associations of the single-nucleotide polymorphism tagging six loci reported in recent GWAS with obesity in young Chinese. Our data also suggest birth weight may significantly modify genetic susceptibility to obesity risk.
This retrospective study was designed to evaluate the value of contrast-enhanced harmonic ultrasonography (CEHU), diffusion-weighted magnetic resonance imaging (DW-MRI) and CEHU plus DW-MRI for the diagnosis of prostate transition-zone (TZ) cancer. In total, 31 TZ cancers in 28 patients and 25 peripheral zone (PZ) cancers in 21 patients without a TZ cancer were evaluated. All patients underwent DW-MRI and CEHU followed by radical prostatectomy. Predictors for the diagnosis of prostate cancer were evaluated in three protocols (CEHU, DW-MRI, CEHU plus DW-MRI). Statistical analysis of the differences between these protocols and receiver operating characteristic (ROC) curve analysis were carried out. CEHU plus DW-MRI had a significantly higher sensitivity, accuracy and negative-predictive value (90.3%, 73.2% and 81.3%, respectively) for TZ cancer than either method alone. The area under the ROC curve values were 0.659, 0.679 and 0.712 for CEHU, DW-MRI, and CEHU plus DW-MRI, respectively. In conclusion, CEHU plus DW-MRI might be a useful protocol for the detection and location of TZ cancer.
Fast Fourier transform-based near-field acoustic holography requires that the measurement aperture should completely enclose the source, which is impractical for large-scale sound sources. Helmholtz equation least-squares method can reconstruct the acoustic field with fewer measurements than fast Fourier transform-based near-field acoustic holography. However, it is not suitable for reconstructing acoustic radiation from multiple sources or a complicated source which consists of several separated parts. To circumvent this difficulty and enhance the reconstruction accuracy, a new data extrapolation method based on the modified Helmholtz equation least-squares method is proposed. The base of this data extrapolation method is a modified Helmholtz equation least-squares method which expresses the acoustic field of a complicated source as the superposition of the acoustic radiation from all of its separated parts. Using the acoustic pressures reconstructed with the modified Helmholtz equation least-squares method, the measurement surface is extended through an iterative procedure. Meanwhile, Tikhonov regularization method together with generalized cross-validation parameter choice method is utilized to treat the ill-posed problem in reconstructions. In the end, taking the extrapolated pressures as input data, the acoustic field can be reconstructed more precisely. Numerical simulation and experimental results demonstrate that this method can significantly enhance the reconstruction accuracy and efficiency.
CD19-targeting chimeric antigen receptor (CAR) T-cell therapeutics is a revolutionary, novel and successful treatment for B-cell malignancies. However, while CD19-CAR-T therapy can obtain high rates of complete responses in these patients, a significant fraction of patients may experience CD19-negative relapse. Moreover, the dependency on T-cell mediated cytotoxicity restricts CAR-T therapy as a patient-specific individualized therapy with severe side effects such as cytokine-release syndrome (CRS). Whether CAR-T therapy can be substituted by a non-T-cell based universal cellular therapy is largely unknown. Surprisingly, we have demonstrated here that T-lymphocytic cells, as well as non-lymphocytic cells, can cause CD19 internalization and subsequent depletion when they are armed with a CD19-recognizing moiety. This CD19 antigen depletion can efficiently induce T-cell independent apoptosis in target cancer cells whose survival is dependent upon CD19 expression, suggesting that CD19 antigen depletion constitutes a crucial tumor destroying mechanism for CD19-CAR-T, especially for its long-term efficacy. We therefore proposed a universal strategy for CRS-free cellular therapeutics, utilizing artificial antigen-recognizing cells (AARC), which can be manufactured universally and standardly as off-the-shelf mesenchymal stromal cells (MSCs) or other types of non-autologous cell expressing anergic CARs. Our results not only uncovered an unrecognized mechanism for CAR-T cytotoxicity and antigen loss, but also shed new insight into a shift in cellular therapeutics from unique patient-specific autologous therapeutics, to universal and standardized allogeneic treatment.
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