Extracting timing and status descriptors for colonoscopy testing from electronic medical records

Colorectal cancer (CRC) screening rates are low despite confirmed benefits. The authors investigated the use of natural language processing (NLP) to identify previous colonoscopy screening in electronic records from a random sample of 200 patients at least 50 years old. The authors developed algorithms to recognize temporal expressions and ‘status indicators’, such as ‘patient refused’, or ‘test scheduled’. The new methods were added to the existing KnowledgeMap concept identifier system, and the resulting system was used to parse electronic medical records (EMR) to detect completed colonoscopies. Using as the ‘gold standard’ expert physicians'' manual review of EMR notes, the system identified timing references with a recall of 0.91 and precision of 0.95, colonoscopy status indicators with a recall of 0.82 and precision of 0.95, and references to actually completed colonoscopies with recall of 0.93 and precision of 0.95. The system was superior to using colonoscopy billing codes alone. Health services researchers and clinicians may find NLP a useful adjunct to traditional methods to detect CRC screening status. Further investigations must validate extension of NLP approaches for other types of CRC screening applications.Colorectal cancer (CRC) is the third most common cancer found in men and women in the USA, and is the second leading cause of cancer deaths.¹ Screening for CRC is recommended for average-risk individuals aged 50 years and older.² Current screening rates, however, are suboptimal; recent national studies report that only 40–60% of eligible patients receive proper screening.^{1 3}Whereas computerized decision support tools have the potential to improve CRC screening rates, the critical challenge is to identify quickly and accurately patients in need of screening. Current methods for determining CRC screening status (patient self-report, physician report, billing data, and manual chart abstraction) are time-consuming, expensive, and often inaccurate. Studies have shown that billing data underestimated CRC screening rates.⁴ Manual chart abstraction is expensive, and references to completed CRC screening tests are often located within the text of clinic notes, making them difficult to find. An Institute of Medicine report highlighted the need for automated data collection systems that could process natural language clinical texts to address challenges such as these.⁵This study investigated the use of a natural language processing (NLP) system to detect the timing and receipt of colonoscopies, the most commonly recommended CRC screening test at many institutions, including the study institution. The authors developed new algorithms to detect the timing and status of colonoscopy references within Vanderbilt Medical Center electronic medical record (EMR) system documents. Vanderbilt''s EMR comprises an integrated longitudinal system that receives data from more than 100 diverse sources such as laboratory and radiology reports, typed and dictated notes, interdisciplinary clinician-maintained problem lists, and inter- and intra-office messaging records.     

实验动物皮肤病原真菌检测方法的改良

目的对实验动物皮肤病原真菌2种培养方法进行了比较。方法将采集到的3只皮肤真菌感染病兔样品经由沙氏平皿法和沙氏试管斜面培养法分别进行培养。结果在3只真菌感染病兔中应用试管斜面法我们只检测到1例皮肤病原真菌阳性,而采用沙氏平皿法3例阳性全部检出。结论结合临床检测经验,我们认为本研究的沙氏平皿法优于沙氏试管斜面法,在实验动物皮肤病原真菌常规检测中具有推广应用价值。     

Polyamines are traps for reactive intermediates in furan metabolism

Furan is toxic and carcinogenic in rodents. Because of the large potential for human exposure, furan is classified as a possible human carcinogen. The detailed mechanism by which furan causes toxicity and cancer is not yet known. Since furan toxicity requires cytochrome P450-catalyzed oxidation of furan, we have characterized the urinary and hepatocyte metabolites of furan to gain insight into the chemical nature of the reactive intermediate. Previous studies in hepatocytes indicated that furan is oxidized to the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), which reacts with glutathione (GSH) to form 2-(S-glutathionyl)succinaldehyde (GSH-BDA). This intermediate forms pyrrole cross-links with cellular amines such as lysine and glutamine. In this article, we demonstrate that GSH-BDA also forms cross-links with ornithine, putrescine, and spermidine when furan is incubated with rat hepatocytes. The relative levels of these metabolites are not completely explained by hepatocellular levels of the amines or by their reactivity with GSH-BDA. Mercapturic acid derivatives of the spermidine cross-links were detected in the urine of furan-treated rats, which indicates that this metabolic pathway occurs in vivo. Their detection in furan-treated hepatocytes and in urine from furan-treated rats indicates that polyamines may play an important role in the toxicity of furan.     

栀蒡热毒平有效组分中栀子苷、牛蒡子苷和黄芩苷在大鼠体内血药浓度测定

目的 建立大鼠血浆中栀蒡热毒平方有效组分中栀子苷、牛蒡子苷和黄芩苷的HPLC血药浓度测定方法.方法 血浆样品采用甲醇-乙腈(1∶ 1)沉淀蛋白,HPLC测定血药浓度.色谱柱为Diamonsil C18柱(4.6 mm×150 mm, 5 μm),流动相乙腈-0.2%磷酸水梯度洗脱,流速1.0 mL/min,检测波长238 nm和278 nm.结果 各成分的最低检测浓度(S/N＞3)在0.23~0.32 mg/L,平均回收率均在85%以上,日内、日间精密度及稳定性的RSD均小于10%.结论 该方法简便、准确,可作为栀蒡热毒平方血药浓度定量分析方法.     

Prediction and <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation of Selected Protease Inhibitor Antiviral Drugs as Inhibitors of Carboxylesterase 1: A Potential Source of Drug-Drug Interactions

Purpose  

To predict and determine whether the protease inhibitors (PIs) nelfinavir, amprenavir, atazanavir, ritonavir, and saquinavir could serve as metabolic inhibitors of the human CES1 (hCES1) using both molecular modeling techniques and in vitro inhibition assays.     

Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer

Background and objective

With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of disease mutation clusters on protein domains by incorporating domain functional annotations to assist in the functional characterization of novel variants.

Methods

Disease mutations aggregated from multiple databases were mapped to domains, and were classified as either cancer- or non-cancer-related. The statistical method for identifying significantly disease-associated domain positions was applied to both sets of mutations and to randomly generated mutation sets for comparison. To leverage the known function of protein domain regions, the method optionally distributes significant scores to associated functional feature positions.

Results

Most disease mutations are localized within protein domains and display a tendency to cluster at individual domain positions. The method identified significant disease mutation hotspots in both the cancer and non-cancer datasets. The domain significance scores (DS-scores) for cancer form a bimodal distribution with hotspots in oncogenes forming a second peak at higher DS-scores than non-cancer, and hotspots in tumor suppressors have scores more similar to non-cancers. In addition, on an independent mutation benchmarking set, the DS-score method identified mutations known to alter protein function with very high precision.

Conclusion

By aggregating mutations with known disease association at the domain level, the method was able to discover domain positions enriched with multiple occurrences of deleterious mutations while incorporating relevant functional annotations. The method can be incorporated into translational bioinformatics tools to characterize rare and novel variants within large-scale sequencing studies.     

IL-17 signaling in host defense against Candida albicans

The discovery of the Th17 lineage in 2005 triggered a major change in how immunity to infectious diseases is viewed. Fungal infections, in particular, have long been a relatively understudied area of investigation in terms of the host immune response. Candida albicans is a commensal yeast that colonizes mucosal sites and skin. In healthy individuals, it is non-pathogenic, but in conditions of immune deficiency, this organism can cause a variety of infections associated with considerable morbidity. Candida can also cause disseminated infections that have a high mortality rate and are a major clinical problem in hospital settings. Although immunity to Candida albicans was long considered to be mediated by Th1 cells, new data in both rodent models and in humans have revealed an essential role for the Th17 lineage, and in particular its signature cytokine IL-17.     

Catecholamines increase conjugative gene transfer between enteric bacteria

The ability of pathogenic bacteria to sense and respond to periods of host stress is critical to their lifestyle. Adrenaline and norepinephrine are catecholamines that mediate acute host stress in vertebrates and invertebrates. Catecholamines are also used as environmental cues to enhance growth, motility and virulence of bacterial pathogens via specific binding receptors. Incidence of multidrug resistant and highly virulent bacterial pathogens is on the rise, and majority of the genes for antimicrobial resistance (AMR) and virulence are carried on horizontally transferable genetic elements. Conjugation machinery offers an efficient method for acquisition of AMR and virulence genes, which may be responsible for propelling the evolution of pathogenic bacteria. Here we show that norepinephrine (NE) at physiological concentrations enhances horizontal gene transfer (HGT) efficiencies of a conjugative plasmid from a clinical strain of Salmonella Typhimurium to an Escherichia coli recipient in vitro. Expressions of plasmid encoded transfer (tra) genes necessary for conjugation were also significantly upregulated in the presence of NE. Phentolamine, an α-adrenergic receptor antagonist, negated the effects of NE on conjugation more strongly than propranolol, a β-adrenergic receptor antagonist. This study for the first time provides evidence that innate mediators of acute host stress may influence evolution and adaptation of bacterial pathogens.     

Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4-/CD8-γδ T-cell large granular lymphocytic leukemia

γδ T-cell large granular lymphocytic (T-LGL) leukemia of the CD4-/CD8- subtype is rare, and data are limited in the literature. This study evaluated the clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 7 cases of CD4-/CD8- γδ T-LGL leukemia. Although this variant shares several clinical and morphologic features with the more common T-LGL leukemias, the incidences of autoimmune hemolytic anemia and pure red cell aplasia are higher. Another striking feature observed in our study was the lack of increased large granular lymphocytes in the peripheral blood in the majority of cases despite prominent bone marrow or splenic involvement. CD4-/CD8- γδ T-LGL leukemia also displays an immunophenotype and pattern of splenic involvement overlapping with hepatosplenic T-cell lymphoma. Clinically, this variant of T-LGL leukemia shows an overall indolent course, but treatment is often required in the initial stages of the disease. Awareness of these features is important for early recognition and accurate diagnosis of patients with CD4-/CD8- γδ T-LGL leukemia.