Combining information from multiple bone turnover markers as diagnostic indices for osteoporosis using support vector machines

Context: Osteoporosis (OP) is a progressive systemic bone disease. Dual-energy X-ray absorptiometry (DXA) is routinely employed and is considered the gold standard method for the diagnosis of OP.

Objective: We aimed to investigate the potential use of combined information from multiple bone turnover markers (BTMs) as a clinical diagnostic tool for OP.

Materials and methods: A total of 9053 Chinese postmenopausal women (2464 primary OP patients and 6589 healthy controls) were recruited. Serum levels of six common BTMs, including BAP, BSP, CTX, OPG, OST and sRANKL were assayed. Models based on support vector machine (SVM) were constructed to explore the efficiency of different combinations of multiple BTMs for OP diagnosis.

Results: Increasing the number of BTMs used in generating the models increased the predictive power of the SVM models for determining the disease status of study subjects. The highest kappa coefficient for the model with one BTM (BAP) compared to DXA was 0.7783. The full model incorporating all six BTMs resulted in a high kappa coefficient of 0.9786.

Conclusion: Our findings showed that although single BTMs were not sufficient for OP diagnosis, appropriate combinations of multiple BTMs incorporated into the SVM models showed almost perfect agreement with the DXA.     

Risks of Biological Invasion on the Belt and Road

1. Download high-res image (299KB)
2. Download full-size image

     

Discovery of 4′-OH-flurbiprofen Mannich base derivatives as potential Alzheimer’s disease treatment with multiple inhibitory activities

A series of 4′-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer’s disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ_1-42 aggregation (65.03% at 25.0?μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro. Furthermore, compound 8n displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 8n as promising candidate for further development of multi-functional drugs against AD.     

Synthesis and biological evaluation of BMS-986120 and its deuterated derivatives as PAR4 antagonists

BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC₅₀ values of 6.30?nM and 6.97?nM, respectively, versus BMS-986120 with an IC₅₀ of 7.80?nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T_1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted.