Enhancing Conformational Sampling for Intrinsically Disordered and Ordered Proteins by Variational Autoencoder.

Intrinsically disordered proteins (IDPs) account for more than 50% of the human proteome and are closely associated with tumors, cardiovascular diseases, and neurodegeneration, which have no fixed three-dimensional structure under physiological conditions. Due to the characteristic of conformational diversity, conventional experimental methods of structural biology, such as NMR, X-ray diffraction, and CryoEM, are unable to capture conformational ensembles. Molecular dynamics (MD) simulation can sample the dynamic conformations at the atomic level, which has become an effective method for studying the structure and function of IDPs. However, the high computational cost prevents MD simulations from being widely used for IDPs conformational sampling. In recent years, significant progress has been made in artificial intelligence, which makes it possible to solve the conformational reconstruction problem of IDP with fewer computational resources. Here, based on short MD simulations of different IDPs systems, we use variational autoencoders (VAEs) to achieve the generative reconstruction of IDPs structures and include a wider range of sampled conformations from longer simulations. Compared with the generative autoencoder (AEs), VAEs add an inference layer between the encoder and decoder in the latent space, which can cover the conformational landscape of IDPs more comprehensively and achieve the effect of enhanced sampling. Through experimental verification, the Cα RMSD between VAE-generated and MD simulation sampling conformations in the 5 IDPs test systems was significantly lower than that of AE. The Spearman correlation coefficient on the structure was higher than that of AE. VAE can also achieve excellent performance regarding structured proteins. In summary, VAEs can be used to effectively sample protein structures.

[Case-control study on locking plates fixation for the treatment of Neer 3-and 4-part proximal humerus fractures].

OBJECTIVE: To compare therapeutic effects of locking plates for the treatment of Neer 3-and 4-part proximal humerus fractures. METHODS: From January 2009 to June 2011, 64 patients with Neer 3-and 4-part proximal humerus fractures were treated with locked plate fixation. There were 39 patients in the 3-part group including 16 males and 23 females, with an average age of (55.12 +/- 12.52) years old; and 25 patients in the 4-part fractures group including 9 males and 16 females,with an average age of (57.92 +/- 13.14) years old. The American Shoulder and Elbow Surgeons score (ASES), visual analogue scale (VAS) and complications were documented for analysis before and after treatment. RESULTS: All the patients had incision healing at the first stage. All the patients were followed up, and the duration ranged from 12 to 30 months, with a mean of 16.5 months. Comparably better shoulder function recovery was achieved in the 3-part fractures group with regard to the ASES (76.14 +/- 14.10 in the 3-part fractures group vs. 65.93 +/- 11.82 in the 4-part fractures group, P < 0.05). Moreover,a statistical difference (P < 0.05) was observed regarding the VAS pain score (2.12 +/- 1.63 in the 3-part fractures group vs. 3.90 +/- 2.21 in the 4-part fractures group). For the complications rate,no statistical difference was noted between 3-part fractures group and 4-part fractures group (20.51% vs. 36.00%). CONCLUSION: The clinical outcomes of the 3-part proximal humerus fractures is better than the 4-part fractures proximal humerus fractures treated with locking plate. Complex proximal humeral fractures treated with locking plates can be achieved a satisfactory outcome when attention is paid to anatomic reduction, stable fixation, proper screws and plate placement, and reasonable functional exercise postoperative.

Antimicrobial resistance and molecular epidemiological characteristics of clinical isolates of Staphylococcus aureus in Changsha area.

BACKGROUND: Increasing prevalence of Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA) has been reported in China. In this study, we investigated the drug resistance characteristic, genetic background, and molecular epidemiological characteristic of S. aureus in Changsha. METHODS: Between January 2006 and December 2008, 293 clinical isolates of S. aureus were collected from 11 hospitals in Changsha and identified by the Vitek-2 system. All the isolates were verified as MRSA by PCR amplification of both femA and mecA genes. K-B disk method was used to test drug sensitivity of S. aureus to antibiotics. Pulsed-field gel electrophoresis (PFGE) was performed for genotypic and homologous analysis of 115 isolates randomly selected from the original 293 clinical S. aureus isolates. RESULTS: S. aureus was highly resistant to penicillin, ampicillin, erythromycin, and clindamycin with resistant rates of 96.6%, 96.6%, 77.1%, and 67.2% respectively. All the isolates were susceptible to tecoplanin, vancomycin, and linezolid. MRSA accounted for 64.8% (190/293) of all the S. aureus strains. The 115 S. aureus isolates were clustered into 39 PFGE types by PFGE typing, with 13 predominant patterns (designated types A to M) accounting for 89 isolates. The most prevalent PFGE type was type A (n = 56, 48.7%) and 100.0% of type A strains were MRSA. PFGE type A included 13 subtypes, and the most prevalent subtype was subtype A1 (46.4%, 26/56). Strains with PFGE type A were isolated from eight hospitals (8/11), and both subtypes A1 and A4 strains were isolated in a university hospital. CONCLUSIONS: Clinical isolates of S. aureus in Changsha were resistant to multiple traditional antibiotics. There was an outbreak of PFGE type A MRSA in this area and the A1 subtype was the predominant epidemic clone. Dissemination of the same clone was an important reason for the wide spread of MRSA.

The use of pleural fluid procalcitonin and C-reactive protein in the diagnosis of parapneumonic pleural effusions: a systemic review and meta-analysis.

BACKGROUND: We aimed to perform a systematic review and meta-analysis of the diagnostic performance of pleural fluid procalcitonin (PCT) or C-reactive protein (CRP) in differentiating parapneumonic effusion in patients with pleural effusion. METHODS: We searched the EMBASE, MEDLINE, and Cochrane database in December 2011. Original studies that reported the diagnostic performance of PCT alone or compared with that of other biomarkers for differentiating the characteristics of pleural effusion were included. RESULTS: We found 6 qualifying studies including 780 patients with suspected parapneumonic effusion and 306 confirmed cases of parapneumonic effusion. Six studies examined the diagnostic performance of pleural fluid PCT, 3 also tested for serum PCT, and another 3 tested for serum CRP. The bivariate pooled sensitivity and specificity were as follows 0.67 (95% confidence interval [CI], 0.54-0.78) and 0.70 (95% CI, 0.63-0.76), respectively, for pleural fluid PCT; 0.65 (95% CI, 0.55-0.74) and 0.68 (95% CI, 0.62-0.74), respectively, for serum PCT; and 0.54 (95% CI, 0.47-0.61) and 0.77 (95% CI, 0.72-0.81), respectively, for serum CRP. There was evidence of significant heterogeneity (I(2)=55.0%) for pleural fluid or serum PCT but not for CRP (I(2)=0.0%). CONCLUSION: The existing literature suggests that both pleural fluid and serum PCT tests have low sensitivity and specificity for differentiating parapneumonic effusion from other etiologies of pleural effusion. Compared with PCT, serum CRP has higher specificity and a higher positive likelihood ratio, and thus, it has a higher rule-in value than PCT.