Quantitative evaluation of recall and precision of CAT Crawler,a search engine specialized on retrieval of Critically Appraised Topics

Background

Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository.

Methods

A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated.

Results

While achieving an identical recall, the meta-search engine showed a precision of 77.26% (±14.45) compared to the individual search engines' 52.65% (±12.0) (p < 0.001).

Conclusion

The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians.

     

Butyrate increases production of human chimeric IgG in CHO-K1 cells whilst maintaining function and glycoform profile

The influence of sodium butyrate on the production and glycosylation of recombinant mouse/human chimeric antibody by transfected CHO-K1 cells was investigated. We selected cells expressing 'wild-type' antibody with a human IgG3 heavy chain and a mutant of this molecule in which Phe 243 is replaced by Ala. These proteins have previously been shown to exhibit very different glycoform profiles with the mutant IgG being comprised of glycoforms having a high galactose and sialic acid content. Cell culture with 0-5 mM butyrate was shown to effect a 2-4-fold increase in antibody production whilst the induction of apoptosis was observed in a dose-dependent manner. The optimal butyrate concentration was observed to be 2 mM. The glycoform profile of each antibody produced in the presence of butyrate was analyzed by HPAEC-PAD and shown to be unchanged, relative to that produced in the absence of butyrate. Biological activity was evaluated by the ability of the antibodies to trigger superoxide generation, through Fc gamma RI, and shown to be independent of production in the presence or absence of butyrate. A similar increase in production was observed for a high antibody-producing cell line when expanded in a hollow fibre bioreactor under low-serum conditions (1%). These results demonstrated that butyrate is of value for increasing the productivity of CHO-K1 for recombinant IgG and does not compromise either glycosylation or biological activity.     

Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain‐of‐function variant: Initial experience

Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain‐of‐function mutations in the regulatory (SUR2) and pore‐forming (Kir6.1) subunits of K_ATP channels, respectively, suggesting that channel‐blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg^–1 kg^–1 day^–1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg^?1 kg^?1day^?1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.     

人FascDNA的克隆及其在大肠杆菌中表达的研究

为获得高质量及充足的Ｆａｓ蛋白，采用ＰＣＲ技术调整Ｆａｓ基因的开放阅读框架，使之与生物素化蛋白基因阅读框架一致；缺失了ＦａｓｃＤＮＡ基因的起始密码子并增加一个大肠杆菌偏性终止密码子，构建ＦａｓｃＤＮＡ和生物素化融合原核表达质粒ＰｉｎＰｏｉｎｔ－Ｆａｓ。将重组质粒转入大肠杆菌ＨＢ１０１，经５００ｍｍｏｌＩＰＴＧ在３７℃条件下诱导４ｈ，ＳＤＳ－ＰＡＧＥ及Ｗｅｓｔｅｒｎ印迹检测融合蛋白在大肠杆菌得以高效表达，表达量为细菌总蛋白的１３．８％。用亲和层析树脂对生物素化融合蛋白进行亲和层析纯化，得到Ｆａｓ重组的蛋白，且表达的Ｆａｓ融合蛋白具有抗体结合活性。此蛋白的表达成功将解决Ｆａｓ膜蛋白不易提取的难题，为深入研究Ｆａｓ提供了良好材料来源     

维生素A阻抑大鼠实验性肝纤维化的病理研究

利用光镜、电镜、免疫组化和形态学定量技术动态研究维生素A对大鼠四氯化碳肝纤维化的抑制作用。结果表明,维生素A可减少四氯化碳中毒大鼠肝内纤维连接蛋白和Ⅰ、Ⅲ型胶原沉积,抑制贮脂细胞向成纤维细胞转化,并可明显地减轻肝纤维化程度。本文还对维生素A抑制肝纤维化的机理及意义作了初步探讨。     

Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow

Our laboratory has characterized a population of stromal cells obtained from adipose tissue termed processed lipoaspirate cells (PLAs). PLAs, like bone-marrow derived mesenchymal stem cells (BM-MSCs), have the capacity to differentiate along the adipogenic, osteogenic, chondrogenic, and myogenic lineages, In order to better characterize these two multi-lineage populations, we examined the surface phenotype of both bone marrow and adipose tissue-derived cells from five patients undergoing surgery. PLA and BM-MSC cells were isolated, subcultivated, and evaluated for cell surface marker expression using flow cytometry. PLA and BM-MSC cells both expressed CD13, CD29, CD44, CD90, CD105, SH-3, and STRO-1. Differences in expression were noted for cell adhesion molecules CD49d (Integrin alpha4), CD54 (ICAM-1), CD34, and CD106 (VCAM-1). While markedly similar, the surface phenotypes of PLA and BM-MSC cells are distinct for several cell adhesion molecules implicated in hematopoietic stem cell homing, mobilization, and proliferation.     

“Smart” Materials for Biosensing Devices: Cell-Mimicking Supramolecular Assemblies and Colorimetric Detection of Pathogenic Agents

Mimicking cell membrane and the biomolecular recognition associated with membranes represents a great technical challenge, yet it has opened doors to innovative diagnostic and therapeutic methods. Our work has focused on design and synthesis of a class of smart materials exploiting biological principals for use in biosensors: these materials are functional polymeric assemblies that mimic the cell membrane and conveniently report the presence of pathogens with a color change. Biologically active cell membrane components are incorporated into conjugated polymers with desirable optical properties and the binding of the target molecules onto the material triggers conformational and electronic shifts that are reflected in a chromatic change (a so-called biochromic shift) that is conveniently observed and recorded. Langmuir–Blodgett thin films and vesicle bilayers provide ideal configurations for precise delivery of the biological binding entity to the sensing interface, and for control of molecular orientation for effective biomolecular interaction. Polydiacetylenic membrane-mimicking materials containing cell surface receptor gangliosides and sialic acid residues, respectively were formulated into these architectures and used for colorimetric detection of bacterial toxins and influenza virus. One advantage of these biochromic conjugated polymer (BCP) sensors is that their molecular recognition and signal transduction functionalities are resident in a single functional unit, making them amenable to convenient microfabrication and use.