Deep learning-based quantitative morphological study of anteroposterior digital radiographs of the lumbar spine.

Background: Morphological parameters of the lumbar spine are valuable in assessing lumbar spine diseases. However, manual measurement of lumbar morphological parameters is time-consuming. Deep learning has automatic quantitative and qualitative analysis capabilities. To develop a deep learning-based model for the automatic quantitative measurement of morphological parameters from anteroposterior digital radiographs of the lumbar spine and to evaluate its performance. Methods: This study used 1,368 anteroposterior digital radiographs of the lumbar spine to train a deep learning model to measure the quantitative morphological indicators, including L1 to L5 vertebral body height (VBH) and L1-L2 to L4-L5 intervertebral disc height (IDH). The means of the manual measurements by three radiologists were used as the reference standard. The parameters predicted by the model were analyzed against the manual measurements using paired t-tests. Percentage of correct key points (PCK), intra-class correlation coefficient (ICC), Pearson correlation coefficient (r), mean absolute error (MAE), root mean square error (RMSE), and Bland-Altman plots were performed to assess the performance of the model. Results: Within the 3-mm distance threshold, the model had a PCK range of 99.77-99.46% for the L1 to L4 vertebrae and 77.37% for the L5 vertebrae. Except for VBH-L5 and IDH_L3-L4, IDH_L4-L5 (P<0.05), the estimated values of the model in the remaining parameters were not statistically significant compared with the reference standard (P>0.05). Except for VBH-L5 and IDH_L4-L5, the model showed good correlation and consistency with the reference standard (ICC =0.84-0.96, r=0.85-0.97, MAE =0.5-0.66, RMSE =0.66-0.95). The model outperformed other models (EfficientDet + Unet, EfficientDet + DarkPose, HRNet, and Unet) in predicting landmarks within a distance threshold of 1.5 to 5 mm. Conclusions: The model developed in this study can automatically measure the morphological parameters of the L1 to L4 vertebrae from anteroposterior digital radiographs of the lumbar spine. Its performance is close to the level of radiologists.

Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression.

Calcium phosphate cements (CPC) are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability, suitable to be used in minimally invasive treatment of bone defects. However the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties, in particular its osteoinductivity. Hyaluronic acid reinforced calcium phosphate cements (HA/CPC) showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its osteoinductivity. In our study, the compressive strength of HA/CPC increased significantly when the cement was added 1% hyaluronic acid (denoted as 1-HA/CPC). In the meantime, hyaluronic acid obviously promoted ALP activity, osteogenic related protein and mRNA expression of hBMSCs (human bone marrow mesenchymal stem cells) in vitro, cement group of HA/CPC with 4% hyaluronic acid adding (denoted as 4-HA/CPC) showed optimal enhancement in hBMSCs differentiation. After being implanted in rat tibial defects, 4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors, comparing to pure CPC and 1-HA/CPC groups. The underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid incorporation. These results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.

Light-field-based absolute phase unwrapping.

Ambiguity caused by a wrapped phase is an intrinsic problem in fringe projection-based 3D shape measurement. Among traditional methods for avoiding phase ambiguity, spatial phase unwrapping is sensitive to sensor noise and depth discontinuity, and temporal phase unwrapping requires additional encoding information that leads to an increase of image sequence acquisition time or a reduction of fringe contrast. Here, to the best of our knowledge, we report a novel method of absolute phase unwrapping based on light field imaging. In a recorded light field under structured illumination, i.e., a structured light field, a wrapped phase-encoded field can be retrieved and resampled in diverse image planes associated with several possible fringe orders in a measurement volume. Then, by leveraging phase consistency constraint in the resampled wrapped phase-encoded field, correct fringe orders can be determined to unwrap the wrapped phase without any additional encoding information. Experimental results demonstrated that the proposed method was suitable for accurate and robust absolute phase unwrapping.

A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells.

The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II. It also significantly inhibited the growth of breast cancer cells. Therefore, the anti-IGF-I/II eAd offers an alternative approach to target both the IGF-1R signaling pathways through the inhibition of IGF-I/II.

Recombinant-fully-human-antibody decorated highly-stable far-red AIEdots for in vivo HER-2 receptor-targeted imaging.

We developed highly bright and stable far-red emissive AIEdots by using a new kind of click-functional PEG grafted amphiphilic polymer to coat hydrophobic AIE-active polymers (PDFDP). Furthermore, an anti-HER2 recombinant fully human antibody was produced and conjugated on the AIEdots via metal-free click chemistry to fabricate in vivo tumor-targeting nanoprobes.

N-terminal α-amino group modification of antibodies using a site-selective click chemistry method.

Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.

Generation of Bispecific Antibodies by Fc Heterodimerization and their Application.

Bispecific antibodies with binding specificities for two different antigens have prompted a lot of interest into their development and application. Currently, more than ten bispecific antibodies have been clinically validated for the treatment of various diseases, including cancers and inflammatory diseases. Intensive studies in antibody engineering drive the generation of different bispecific antibody formats that differ in size and shape. However, the most prominent formats, such as IgG-single-chain (sc) Fv or dual-variable domain (DVD) IgG, deviating from the natural IgG structure, may lead to manufacturing difficulties or increase the potential risk of immunogenicity. Thus, the recent efforts focus on the development of bispecific antibodies by Fc heterodimerization that maintain the native structure of the antibody IgG molecule. This review summarizes the various techniques and methods to generate bispecific antibody molecules with Fc heterodimerization, and discusses perspectives of their application.