Two missense variants in UHRF1BP1 are independently associated with systemic lupus erythematosus in Hong Kong Chinese

UHRF1BP1 encodes a highly conserved protein with unknown function. Previously, a coding variant in this gene was found to be associated with systemic lupus erythematosus (SLE) in populations of European ancestry (rs11755393, R454Q, P=2.22 x 10??, odds ratio=1.17). In this study, by a combination of genome-wide study and replication involving a total of 1230 patients and 3144 controls, we confirmed the association of this coding variant to SLE in Hong Kong Chinese. We also identified another coding variant in this gene that independently contributes to SLE susceptibility (rs13205210, M1098T, P=4.44 x 10??, odds ratio=1.49). Cross-population confirmation establishes the involvement of this locus in SLE and indicates that distinct alleles are contributing to disease susceptibility.     

Deep Learning-Assisted Diagnosis of Pediatric Skull Fractures on Plain Radiographs

ObjectiveTo develop and evaluate a deep learning-based artificial intelligence (AI) model for detecting skull fractures on plain radiographs in children.Materials and MethodsThis retrospective multi-center study consisted of a development dataset acquired from two hospitals (n = 149 and 264) and an external test set (n = 95) from a third hospital. Datasets included children with head trauma who underwent both skull radiography and cranial computed tomography (CT). The development dataset was split into training, tuning, and internal test sets in a ratio of 7:1:2. The reference standard for skull fracture was cranial CT. Two radiology residents, a pediatric radiologist, and two emergency physicians participated in a two-session observer study on an external test set with and without AI assistance. We obtained the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity along with their 95% confidence intervals (CIs).ResultsThe AI model showed an AUROC of 0.922 (95% CI, 0.842–0.969) in the internal test set and 0.870 (95% CI, 0.785–0.930) in the external test set. The model had a sensitivity of 81.1% (95% CI, 64.8%–92.0%) and specificity of 91.3% (95% CI, 79.2%–97.6%) for the internal test set and 78.9% (95% CI, 54.4%–93.9%) and 88.2% (95% CI, 78.7%–94.4%), respectively, for the external test set. With the model’s assistance, significant AUROC improvement was observed in radiology residents (pooled results) and emergency physicians (pooled results) with the difference from reading without AI assistance of 0.094 (95% CI, 0.020–0.168; p = 0.012) and 0.069 (95% CI, 0.002–0.136; p = 0.043), respectively, but not in the pediatric radiologist with the difference of 0.008 (95% CI, -0.074–0.090; p = 0.850).ConclusionA deep learning-based AI model improved the performance of inexperienced radiologists and emergency physicians in diagnosing pediatric skull fractures on plain radiographs.     

腔隙性脑梗塞患者脑内微出血的发生、分布及其意义

目的 探讨脑内微出血在腔隙性梗塞病人中的发生率及在脑内各区域的分布情况,以及与其他微小血管病变包括脑白质改变和腔隙性梗塞之间的关系。方法 连续入选腔隙性脑梗塞病人82例。记录一般临床资料、实验室检查及神经精神功能评分包括入院时的美国国立卫生研究院卒中评分(NIHSS)和发病三个月时的Barthel生活指数(BI)和简易精神状态量表(MMSE)。所有病人均进行头颅MR检查观察脑内微出血的数目及部位,脑白质改变的程度和腔隙性脑梗塞的数目及部位。数据处理均采用SPSS软件进行。结果 22例患者(27％)存在脑内微出血,数目由1～42个,分布于脑内不同部位包括皮层-皮层下、丘脑基底节区、小脑和脑干。微出血的数目与腔隙性梗塞的数目以及脑白质改变的程度显著相关(r=0.297,0.552;P=0.007,<0.001)。3个月时微出血组病人的MMSE和BI有低于无微出血组病人的趋势(22.56 vs 24.53,16.71 vs 19.11),但无统计学差异(P=0.162,0.052)。结论 脑内微出血在腔隙性脑梗塞中发生率较高,且与脑白质改变的严重程度以及腔隙性梗塞的数目相关。提示脑内微出血是另外一种微小血管病损的标志,可能代表着更为严重的小血管壁的损害,更为直接地提示出血倾向,在腔隙性脑梗塞的治疗及预防过程中应予以相应的重视。     

Understanding the role of tumor stem cells in glioblastoma multiforme: a review article

It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.     

Water-free microencapsulation of proteins within PLGA microparticles by spray drying using PEG-assisted protein solubilization technique in organic solvent

Poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles encapsulating therapeutic proteins were prepared under a water-free formulation condition. Bovine serum albumin (BSA) and recombinant human growth hormone (rhGH) were homogeneously solubilized as nano-scale complexes in methylene chloride phase by using polyethylene glycol (PEG) as a complex-forming agent. The organic phase containing dissolved PLGA and PEG/protein complexes was directly spray dried to obtain PLGA microparticles encapsulating proteins. They exhibited sustained release profiles of BSA and rhGH up to 30 days with reduced initial bursts. The released protein molecules from the microparticles maintained structural integrity without aggregation, suggesting that the current single-step protein microencapsulation method without using water could be potentially applied for sustained delivery of a wide range of therapeutic protein drugs that are not soluble in organic solvents.     

Drug-related problems in hospitalized patients with HIV infection.

PURPOSE: The type and number of drug-related problems that commonly occur in hospitalized patients with HIV were studied. METHODS: The medical records of HIV-infected patients who were receiving antiretroviral therapy at the time of hospital admission between January 1, 2005, and August 31, 2006, were reviewed. Patients age 18 years or older who had received at least one dose of an antiretroviral for an HIV-related indication during their hospitalization were included in the study. Patients' medical records were evaluated to identify drug-related problems and adverse drug events secondary to antiretroviral therapy. RESULTS: Eighty-three patients were eligible for study inclusion. A total of 176 drug-related problems were identified. The most common drug-related problem identified among medication orders reviewed was inappropriate dosing. Of the 251 orders for antiretroviral agents, 57 drugs were inappropriately dosed. The most common drug-related problems among patients were drug-drug interactions and incomplete antiretroviral regimens. There was no significant difference in the mean length of stay between patients with or without drug-related problems. Admission by physicians who were not infectious diseases specialists was an independent risk factor for having at least one drug-related problem during hospitalization (odds ratio, 3.83; 95% confidence interval, 1.08-13.54). CONCLUSION: A majority of HIV-infected patients at one institution had at least one drug-related problem at hospital admission. The most common problem observed among the medication orders reviewed was inappropriate dosing. The most common drug-related problems observed among patients were drug-drug interactions and incomplete antiretroviral regimens.