Prediction model for spinal cord injury in spinal tuberculosis patients using multiple machine learning algorithms: a multicentric study.

Spinal cord injury (SCI) is a prevalent and serious complication among patients with spinal tuberculosis (STB) that can lead to motor and sensory impairment and potentially paraplegia. This research aims to identify factors associated with SCI in STB patients and to develop a clinically significant predictive model. Clinical data from STB patients at a single hospital were collected and divided into training and validation sets. Univariate analysis was employed to screen clinical indicators in the training set. Multiple machine learning (ML) algorithms were utilized to establish predictive models. Model performance was evaluated and compared using receiver operating characteristic (ROC) curves, area under the curve (AUC), calibration curve analysis, decision curve analysis (DCA), and precision-recall (PR) curves. The optimal model was determined, and a prospective cohort from two other hospitals served as a testing set to assess its accuracy. Model interpretation and variable importance ranking were conducted using the DALEX R package. The model was deployed on the web by using the Shiny app. Ten clinical characteristics were utilized for the model. The random forest (RF) model emerged as the optimal choice based on the AUC, PRs, calibration curve analysis, and DCA, achieving a test set AUC of 0.816. Additionally, MONO was identified as the primary predictor of SCI in STB patients through variable importance ranking. The RF predictive model provides an efficient and swift approach for predicting SCI in STB patients.

Which surgery is better for obese patients with lumbar degenerative diseases: open TLIF or Endo-LIF? A retrospective matched case-control study.

OBJECTIVE: This study aimed to evaluate short-term clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (Endo-LIF) in the treatment of obese patients with lumbar degenerative diseases (LDD). METHODS: Patients who underwent single-level lumbar fusion surgery from July 2020 to July 2022 were retrospectively analyzed in this study. The main inclusion criterion was a body mass index (BMI) ≥30kg/m2. A matched case-control design was conducted to compare the short-term outcomes between the Endo-LIF and transforaminal lumbar interbody fusion (TLIF) in obese patients. Cases were defined as those who underwent Endo-LIF, and controls were matched from those patients with open TLIF according to corresponding matched criteria. Surgeon satisfaction was evaluated by questionnaires at the end of each surgery, patient satisfaction and their willingness to undergo the same surgery again were collected. RESULTS: Two groups of patients were successfully completed surgery. In comparison with the open TLIF group, the Endo-LIF group had significantly less blood loss, less time to postoperative ambulation, less postoperative complications and shorter hospitalization days, but longer operation time and x-ray exposure times. The satisfaction of surgeons and patients in Endo-LIF group significantly were superior to open TLIF group. CONCLUSION: Endo-LIF is a safe and effective surgery in the treatment of obese patients. Although this procedure needs longer operation time and x-ray exposure times, it still maybe a promising option for obese patients with LDD.

An In Situ Prepared Comb-like Polycaprolactone-Based Gel Electrolyte for High-Performance Lithium Metal Batteries.

Herein, we present the synthesis and electrochemical performance of a comb-like polycaprolactone-based gel electrolyte from acrylate terminated polycaprolactone oligomers and liquid electrolyte for high-voltage lithium metal batteries. The ionic conductivity of this gel electrolyte at room temperature was measured to be 8.8 × 10-3 S cm-1, which is an exceptionally high value that is more than sufficient for the stable cycling of solid-state lithium metal batteries. The Li+ transference number was detected to be 0.45, facilitating the prohibition of concentration gradients and polarization, thereby prohibiting lithium dendrite formation. In addition, the gel electrolyte exhibits high oxidation voltage up to 5.0 V vs. Li+/Li and perfect compatibility against metallic lithium electrodes. The superior electrochemical properties provide the LiFePO4-based solid-state lithium metal batteries with excellent cycling stability, displaying a high initial discharge capacity of 141 mAh g-1 and an extraordinary capacity retention exceeding 74% of its initial specific capacity after being cycled for 280 cycles at 0.5C at room temperature. This paper presents a simple and effective in situ preparation process yielding an excellent gel electrolyte for high-performance lithium metal battery applications.

Dynamic covalent crosslinked hyaluronic acid hydrogels and nanomaterials for biomedical applications.

Hyaluronic acid (HA), one of the main components of the extracellular matrix (ECM), is extensively used in the design of hydrogels and nanoparticles for different biomedical applications due to its critical role in vivo, degradability by endogenous enzymes, and absence of immunogenicity. HA-based hydrogels and nanoparticles have been developed by utilizing different crosslinking chemistries. The development of such crosslinking chemistries indicates that even subtle differences in the structure of reactive groups or the procedure of crosslinking may have a profound impact on the intended mechanical, physical and biological outcomes. There are widespread examples of modified HA polymers that can form either covalently or physically crosslinked biomaterials. More recently, studies have been focused on dynamic covalent crosslinked HA-based biomaterials since these types of crosslinking allow the preparation of dynamic structures with the ability to form in situ, be injectable, and have self-healing properties. In this review, HA-based hydrogels and nanomaterials that are crosslinked by dynamic-covalent coupling (DCC) chemistry have been critically assessed.

Impact of Hydrogel Cross-Linking Chemistry on the in Vitro and in Vivo Bioactivity of Recombinant Human Bone Morphogenetic Protein-2.

Designing strategies to deliver functional proteins at physiologically relevant concentrations using chemically cross-linked biocompatible hydrogels is a major field of research. However, the impact of cross-linking chemistry on the encapsulated protein bioactivity is rarely studied. Here we examine the two well-known cross-linking reactions namely; hydrazone cross-linking chemistry and thiol-Michael addition reaction to form hyaluronic acid (HA) hydrogels. As a therapeutic protein, we employed recombinant human bone morphogenetic protein-2 (rhBMP-2) for this study. Incubation of rhBMP-2 with HA functionalized with a thiol diminished phosphorylation of Smad 1/5/8, a signal transducer for osteogenic differntiation, whereas an aldehyde functionalized HA had no effect. This indicates that thiol functionalized polymers indeed has an impact on protein function. To validate this result in an in vivo setting we performed BMP-2 induced bone formation in a rat ectopic model. These experiments revealed that the hydrazone-cross-linked HA-hydrogel induced significantly higher bone formation (18.90 ± 4.25 mm3) as compared to the HA-thiol-Michael hydrogels (1.25 ± 0.52 mm3) after 8 weeks as determined by micro-computed tomography. The histological examination of the neo-bone indicated that hydrazone-hydrogels promoted a better quality of bone formation with improved mineralization and collagen formation as compared to the thiol-Michael hydrogels. We believe such a direct comparison of two cross-linking chemistries will provide new insight for developing biomaterials for protein delivery for in vivo applications.

Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation.

Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.

Saline Accelerates Oxime Reaction with Aldehyde and Keto Substrates at Physiological pH.

We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration-dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most biofriendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

Early warning for human mental sub-health based on fMRI data analysis: an example from a seafarers' resting-data study.

Effective mental sub-health early warning mechanism is of great significance in the protection of individual mental health. The traditional mental health assessment method is mainly based on questionnaire surveys, which may have some uncertainties. In this study, based on the relationship between the default mode network (DMN) and the mental health status, we proposed a human mental sub-health early warning method by utilizing two-fold support vector machine (SVM) model, where seafarers' fMRI data analysis was utilized as an example. The method firstly constructed a structural-functional DMN template by combining the anatomical automatic labeling template with the functional DMN extracted by independent component analysis. Then, it put forward a two-fold SVM-based classifier, with one-class SVM utilized for the training of the initial classifier and two-class SVM utilized to refine the classification performance, to identify seafarers' mental health status by utilizing the correlation coefficients (CCs) among the areas of structural-functional DMN as the features. The experimental results showed that the proposed model could discriminate the seafarers with DMN function alteration from the healthy control (HC) effectively, and further the results demonstrated that when compared with the HC group, the brain functional disorders of the mental sub-healthy seafarers mainly manifested as follows: the functional connectivity of DMN had obvious alteration; the CCs among the different DMN regions were significant lower; the regional homogeneity decreased in parts of the prefrontal cortex and increased in multi-regions of the parietal, temporal and occipital cortices; the fractional amplitude of low-frequency fluctuation decreased in parts of the prefrontal cortex and increased in parts of the parietal cortex. All of the results showed that fMRI-based analysis of brain functional activities could be effectively used to distinguish the mental health and sub-health status.

Insights into the mechanism and catalysis of oxime coupling chemistry at physiological pH.

The dynamic covalent-coupling reaction involving α-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of α-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a ∼14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

Cycloartane triterpenoids and their glycosides from the rhizomes of Cimicifuga foetida.

A phytochemical study on the rhizomes of Cimicifuga foetida resulted in the isolation of two new cycloartane triterpenoids (1 and 2), eight new cycloartane glycosides (3-10), and six known cycloartane glycoside analogues (11-16). The structures of 1-10 were determined by application of spectroscopic methods, with the absolute configuration of 1 determined by X-ray crystallography. Compounds 1-6, as three pairs of epimers at C-10 and C-24, belong to a seven-membered-ring variant of 9,10-seco-9,19-cycloartane triterpenoids, and glycosides 3-10 were found to be 3-O-ß-D-xylopyranosides. The cytotoxicity of the isolates was evaluated against five selected human tumor cell lines, and the known compounds 15 and 16 showed cytotoxicity against the hepatocellular carcinoma SMMC-7721 cell line with IC50 values of 5.5 and 6.3 µM, respectively.

Mild and efficient strategy for site-selective aldehyde modification of glycosaminoglycans: tailoring hydrogels with tunable release of growth factor.

Aldehydes have been used as an important bioorthogonal chemical reporter for conjugation of large polymers and bioactive substances. However, generating aldehyde functionality on carbohydrate-based biopolymers without changing its native chemical structure has always persisted as a challenging task. The common methods employed to achieve this require harsh reaction conditions, which often compromise the structural integrity and biological function of these sensitive molecules. Here we report a mild and simple method to graft aldehydes groups on glycosaminoglycans (GAGs) in a site-selective manner without compromising the structural integrity of the biopolymer. This regio-selective modification was achieved by conjugating the amino-glycerol moiety on the carboxylate residue of the polymer, which allowed selective cleavage of pendent diol groups without interfering with the C2-C3 diol groups of the native glucopyranose residue. Kinetic evaluation of this reaction demonstrated significant differences in second-order reaction rate for periodate oxidation (by four-orders of magnitude) between the two types of vicinal diols. We employed this chemistry to develop aldehyde modifications of sulfated and nonsulfated GAGs such as hyaluronic acid (HA), heparin (HP), and chondroitin sulfate (CS). We further utilized these aldehyde grafted GAGs to tailor extracellular matrix mimetic injectable hydrogels and evaluated its rheological properties. The composition of the hydrogels was also found to modulate release of therapeutic protein such as FGF-2, demonstrating controlled release (60%) for over 14 days. In short, our result clearly demonstrates a versatile strategy to graft aldehyde groups on sensitive biopolymers under mild conditions that could be applied for various bioconjugation and biomedical applications such as drug delivery and regenerative medicine.

Poly[[[silver(I)-µ-1,4-bis-[(imidazol-1-yl)meth-yl]benzene-κN:N-silver(I)-µ-1,4-bis-[(imidazol-1-yl)meth-yl]benzene-κN:N] 4,4'-diazenediyldibenzoate] dihydrate].

In the title compound, [Ag(2)(C(14)H(14)N(4))(2)](C(14)H(8)N(2)O(4))·2H(2)O, each of the two unique Ag(+) ions is two-coordinated by two N atoms from two different 1,4-bis-[(imidazol-1-yl)meth-yl]benzene ligands in an almost linear fashion [N-Ag-N = 170.34 (10) and 160.25 (10)°]. The 4,4'-diazenediyldibenzoate anions do not coordinate to Ag. O-H⋯O hydrogen bonds stabilize the crystal structure.

[Mortality of HIV infected clients treated with methadone maintenance treatment in Yili Kazakh autonomous prefecture].

OBJECTIVE: To investigate the mortality of HIV infected clients from methadone maintenance treatment (MMT) clinics in Yili Kazakh autonomous prefecture as well as the factors associated with mortality of HIV infected clients. METHODS: A retrospective cohort study was performed. Data of 860 cases were collected from National Methadone Maintenance Treatment database, National AIDS/HIV database and antiretroviral therapy (ART) treatment database for adults. Information collected included demographic information of HIV infected clients, methadone daily treatment information, CD4 testing information, ART treatment information and death information. Recruiting began from August, 2005 through May, 2011. Cox proportional regression was used to identify factors associated with mortality. The proportional hazard assumption was assessed using Schoenfeld's residuals test. Missing values were imputed using the multiple linear regression method. R software (version 2.13.0) was used to perform data analysis. RESULTS: A total of 860 HIV positive MMT clients were analyzed. The methadone dose for study subjects was (38.2 ± 20.7) mg/d. 27.8% (239/860) of study subjects participated in ART treatment, 38.7% (333/860) had never tested for CD4 count. The age for study subjects was (32.9 ± 6.4) years old. Among all these subjects, 67.3% (579/860) were married. During the observation period, 151 deaths were observed in 2192.9 person years. The average observation time was 2.6 year for each subject. The all-cause mortality rate was 68.9‰. Cox proportion model showed that ART treatment (HR = 0.53, 95%CI: 0.32 - 0.88), baseline CD4 count at 200 - 350 cells/µl (HR = 0.35, 95%CI: 0.20 - 0.60), baseline CD4 count more than 350 cells/µl (HR = 0.16, 95%CI: 0.09 - 0.29), and marriage (HR = 0.55, 95%CI: 0.37 - 0.82) were associated with less mortality compared with control group. Age (more than 45 years old) (HR = 5.20, 95%CI: 2.60 - 10.20) and sharing needles (HR = 1.40, 95%CI: 1.02 - 2.00) were risk factors associated with death. CONCLUSION: High mortality rate was observed among HIV infected clients. Methadone clinic should provide ART treatment or ART referral services.