Effects of the epigenetic drug MS-275 on the release and function of exosome-related immune molecules in hepatocellular carcinoma cells

Background

Tumor-derived exosomes have been viewed as a source of tumor antigens that can be used to induce anti-tumor immune responses. In the current study, we aim to investigate the regulatory effect of the epigenetic drug MS-275 on hepatoma G2 (HepG2) cell-derived exosomes, especially for their immunostimulatory properties and alteration of some non-specific immune protein expression, such as heat shock protein (HSP) 70, major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) and MICB.

Methods

MS-275 was used to modulate the secretion of exosomes in human HepG2 cells, and exosomes from untreated HepG2 cells served as negative controls. RT-PCR was used to test the expression of HSP70, MICA and MICB in HepG2 cells. Immunogold labeling of exosomes and western blotting analysis were carried out to compare the expression of HSP70, MICA and MICB proteins in exosomes with or without MS-275 treatment. A natural killer (NK) cell cytotoxicity assay and peripheral blood mononuclear cell (PBMC) proliferation assay were used to evaluate the effect of MS-275 on the immunostimulatory ability of exosomes.

Results

Immunogold labeling and western blot analysis showed that modification of MS-275 increased the expression of HSP70 and MICB in exosomes. RT-PCR showed the mRNA levels of HSP70 and MICB were upregulated in HepG2 cells and were consistent with their protein levels in exosomes. The exosomes modified by MS-275 could significantly increase the cytotoxicity of NK cells and proliferation of PBMC (P < 0.05).

Conclusions

The non-specific immune response of exosomes derived from HepG2 cells could be enhanced with treatment by the histone deacetylase inhibitor (HDACi) drug MS-275; this could provide a potential tumor vaccine strategy against liver cancer.     

Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants

Objective

Although trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome.

Materials and methods

An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer''s disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism.

Results

Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001).

Discussion

The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein–protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP).

Conclusion

These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as ‘unique personal variants’. They also provide insight for identifying novel targets, for repositioning drugs, and for personal therapeutics.     

Bi-directional semantic similarity for gene ontology to optimize biological and clinical analyses

Background

Semantic similarity analysis facilitates automated semantic explanations of biological and clinical data annotated by biomedical ontologies. Gene ontology (GO) has become one of the most important biomedical ontologies with a set of controlled vocabularies, providing rich semantic annotations for genes and molecular phenotypes for diseases. Current methods for measuring GO semantic similarities are limited to considering only the ancestor terms while neglecting the descendants. One can find many GO term pairs whose ancestors are identical but whose descendants are very different and vice versa. Moreover, the lower parts of GO trees are full of terms with more specific semantics.

Methods

This study proposed a method of measuring semantic similarities between GO terms using the entire GO tree structure, including both the upper (ancestral) and the lower (descendant) parts. Comprehensive comparison studies were performed with well-known information content-based and graph structure-based semantic similarity measures with protein sequence similarities, gene expression-profile correlations, protein–protein interactions, and biological pathway analyses.

Conclusion

The proposed bidirectional measure of semantic similarity outperformed other graph-based and information content-based methods.     

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice

Objective

To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl₄ intoxicated Swiss albino mice.

Methods

First group of mice (n=5) received CCl₄ treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl₄ (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups.

Results

The result of present study suggested that CCl₄ administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl₄ intoxicated mice. Apart from damaging the liver system, CCl₄ also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl₄ on the non specific host response in the peritoneal macrophages of CCl₄ intoxicated mice.

Conclusions

In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.     

Integrated gene network analysis and text mining revealing PIK3R1 regulated by miR-127 in human bladder cancer

Background

Cancer is the result of a complex multistep process that involves the accumulation of sequential alterations of several genes, including those encoding microRNAs (miRNAs) that have critical roles in the regulation of gene expression.In this study, we aimed to predict potential mechanisms of bladder cancer related miRNAs and target genes by bioinformatics analyses.

Methods

Here we used the method of text mining to identify nine miRNAs in bladder cancer and adopted protein-protein interaction analysis to identify interaction sites between these miRNAs and related-target genes.

Results

There are two relationship types between bladder cancer and its related miRNAs: causal and unspecified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment test showed that there were three pathways related to four miRNA targeted genes. The remaining five miRNAs annotated to disease are not enriched in the KEGG pathways. Of these, PIK3R1 is the overlapping gene among 38 genes in the cancer and bladder cancer pathways.

Conclusions

These findings provide new insights into the role of miRNAs in the pathway of cancer and give us a hypothesis that miR-127 might play a similar role in regulation and control of PIK3R1.     

Profiles of the auditory epithelia related microRNA expression in neonatal and adult rats

Background

The impact of miRNA differential expression on the auditory epithelium stem cell development in postnatal rats is not clear. The present study was designed to analyze miRNA expression in the organ of Corti of neonatal and adult rats.

Methods

The cochleae of newborn (P0) and adult (P30) Sprague-Dawley rats were dissected in cold PBS to collect the sensory epithelia. Small RNAs were extracted using the mirVana RNA Isolation kit. Then, miRNA expression profiling was performed with RNAs from three newborns and three adult rats utilizing the TaqMan Array Rodent MicroRNA Panel.

Results

Eighteen miRNAs were found be differentially expressed, 16 were unregulated in mature cochleae with the fold changes ranging from 17 to 600 folds. The expression levels of two miRNAs were reduced in the mature rat cochleae. GO analysis and signaling pathway analysis revealed the potential involvement of the miRNAs in the regulation of Wnt and TGF-β signaling pathways in hair cell development.

Conclusions

Our results provided novel insights into the functional significance of miRNAs in the basilar membrane cells development, and revealed the potential importance of miRNAs in the hair cell by regulation of Wnt and TGF-β signaling.     

Can poison control data be used for pharmaceutical poisoning surveillance?

Objective

To determine the association between the frequencies of pharmaceutical exposures reported to a poison control center (PCC) and those seen in the emergency department (ED).

Design

A statewide population-based retrospective comparison of frequencies of ED pharmaceutical poisonings with frequencies of pharmaceutical exposures reported to a regional PCC. ED poisonings, identified by International Classification of Diseases, Version 9 (ICD-9) codes, were grouped into substance categories. Using a reproducible algorithm facilitated by probabilistic linkage, codes from the PCC classification system were mapped into the same categories. A readily identifiable subset of PCC calls was selected for comparison.

Measurements

Correlations between frequencies of quarterly exposures by substance categories were calculated using Pearson correlation coefficients and partial correlation coefficients with adjustment for seasonality.

Results

PCC reported exposures correlated with ED poisonings in nine of 10 categories. Partial correlation coefficients (r_p) indicated strong associations (r_p>0.8) for three substance categories that underwent large changes in their incidences (opiates, benzodiazepines, and muscle relaxants). Six substance categories were moderately correlated (r_p>0.6). One category, salicylates, showed no association.

Limitations

Imperfect overlap between ICD-9 and PCC codes may have led to miscategorization. Substances without changes in exposure frequency have inadequate variability to detect association using this method.

Conclusion

PCC data are able to effectively identify trends in poisonings seen in EDs and may be useful as part of a pharmaceutical poisoning surveillance system. The authors developed an algorithm-driven technique for mapping American Association of Poison Control Centers codes to ICD-9 codes and identified a useful subset of poison control exposures for analysis.     

Evaluation of anti-apoptotic activity of different dietary antioxidants in renal cell carcinoma against hydrogen peroxide

Objective

To evaluate the anti-apoptotic and radical scavenging activities of dietary phenolics, namely ascorbic acid,α-tocopherol acetate, citric acid, salicylic acid, and estimate H₂O₂-induced apoptosis in renal cell carcinoma cells.

Methods

The intracellular antioxidant potency of antioxidants was investigated. H₂O₂-induced apoptosis in RCC-26 was assayed with the following parameters: cell viability (% apoptosis), nucleosomal damage and DNA fragmentation, bcl-2 levels and flow cytometery analysis (ROS production evaluation).

Results

The anticancer properties of antioxidants such as ascorbic acid, α-tocopherol acetate, citric acid, salicylic acid with perdurable responses were investigated. It was observed that these antioxidants had protective effect (anti-apoptotic activity) against hydrogen peroxide (H₂O₂) in renal cell carcinoma (RCC-26) cell line.

Conclusions

This study reveals and proves the anticancer properties. However, in cancer cell lines anti-apoptotic activity can indirectly reflect the cancer promoter activity through radicals scavenging, and significantly protect nucleus and bcl-2.     

Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin

Objective

To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.

Methods

The cytotoxic properties, 50% inhibition concentration (IC₅₀) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.

Results

Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC₅₀ value of 11 µmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.

Conclusions

Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC₅₀ of 11 µmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.     

Genetic analysis of maturity and flowering characteristics in maize (Zea mays L.)

Objective

To elucidate the pattern of inheritance and determine the relative magnitude of various genetic effects for maturity and flowering attributes in subtropical maize.

Methods

Four white grain maize inbred lines from flint group of corn, two with late maturity and two with early maturity, were used. These contrasting inbred lines were crossed to form four crosses. Six generations (P₁, P₂, F₁, F₂, BC₁, and BC₂) were developed for each individual cross. These were evaluated in triplicate trial for two consecutive years.

Results

Both dominance gene action and epistatic interaction played major role in governing inheritance of days to pollen shedding, 50% silking, anthesis silking interval and maturity.

Conclusions

Preponderance of dominance gene action for these traits indicated their usefulness in hybrid programs of subtropical maize.     

Research and applications: The intended and unintended consequences of communication systems on general internal medicine inpatient care delivery: a prospective observational case study of five teaching hospitals

Background

Effective clinical communication is critical to providing high-quality patient care. Hospitals have used different types of interventions to improve communication between care teams, but there have been few studies of their effectiveness.

Objectives

To describe the effects of different communication interventions and their problems.

Design

Prospective observational case study using a mixed methods approach of quantitative and qualitative methods.

Setting

General internal medicine (GIM) inpatient wards at five tertiary care academic teaching hospitals.

Participants

Clinicians consisting of residents, attending physicians, nurses, and allied health (AH) staff working on the GIM wards.

Methods

Ethnographic methods and interviews with clinical staff (doctors, nurses, medical students, and AH professionals) were conducted over a 16-month period from 2009 to 2010.

Results

We identified four categories that described the intended and unintended consequences of communication interventions: impacts on senders, receivers, interprofessional collaboration, and the use of informal communication processes. The use of alphanumeric pagers, smartphones, and web-based communication systems had positive effects for senders and receivers, but unintended consequences were seen with all interventions in all four categories.

Conclusions

Interventions that aimed to improve clinical communications solved some but not all problems, and unintended effects were seen with all systems.     

Health Professionals Expose TB Patients to Stigmatization in Society: Insights from Communities in an Urban District in Ghana

Objectives

To determine how the activities and attitudes of health professionals expose TB patients to stigmatization in the community.

Design

Qualitative research approach using individual interviews and focus groups

Setting

Shama Ahanta East Metropolitan district in the western region of Ghana

Participants

Members in nine communities in the district

Outcome measures

Words and statements that depict how activities and attitudes of health professionals may expose TB patients to stigmatization

Results

Five interrelated ways by which activities and attitudes of health professionals may expose TB patients to stigmatization in the community were identified in data: TB control practices; fear-based responses to TB; inappropriate health education messages; medical licensing for sellers; and prohibition of burial rites.

Conclusions

The findings may explain the diagnostic delay and low TB case detection rate in Ghana. This calls for intensification of education on TB and regular organization of refresher courses and possibly retraining of health professionals in TB control and management. When health professionals are seen to be treating TB patients as ‘normal’ individuals, it has the potential of changing the society''s perception about the disease.     

Antiglycation,antioxidant and toxicological potential of polyphenol extracts of alligator pepper,ginger and nutmeg from Nigeria

Objective

To evaluate the antioxidant and antiglycation potential of polyphenols from three spices; alligator pepper, ginger and nutmeg.

Methods

Polyphenol extracts of these spices were subjected to brine-shrimp lethality assay, phytotoxicity test, DPPH and superoxide anion radical scavenging as well as BSA-glucose antiglycation assay.

Results

Results obtained showed that polyphenol extract of ginger has the highest antioxidant potential with IC₅₀ 0.075 and 0.070 mg/mL for DPPH and superoxide anion radical scavenging assay while alligator pepper displayed highest antiglycation activity with IC₅₀ 0.125 mg/mL. However, nutmeg extract exhibited weakest cytotoxic and phytotoxic potential with LD₅₀ 4359.70 and 1490 µg/mL respectively.

Conclusions

It can be concluded that the polyphenol extracts of alligator pepper, ginger and nutmeg displayed good antioxidant as well as antiglycation potential and are safe for consumption.     

Analysis of chemical composition and bioactive property evaluation of Indian propolis

Objective

To analyze the chemical composition and to evaluate the bioactive potential of hydroalocoholic extract of propolis.

Methods

Ethanol extract of propolis was analyzed by GC-MS, HPTLC and HPLC methods and in vitro antioxidant, anticholinesterase and cytotoxicity assay were performed.

Results

GC-MS analysis revealed the presence of fatty acids, alcohols, and quercetin. Quercetin was identified and quantified by HPTLC and HPLC methods. Dose dependent DPPH and hydroxyl radical scavenging activity of hydroalcoholic extract of propolis was calculated as 16.20 and 34.33 µg/mL respectively. Inhibition of lipid peroxidation was significant and the IC₅₀ value was calculated as 55.56µg/mL. Anticholinesterase activity was less observed. The cytotoxic activity against both breast (MCF-7) and lung cancer (A543) cell lines were significant and the IC₅₀ value was calculated as 10 and 13 µg/mL respectively.

Conclusions

These findings showed that bioactive compounds present in propolis will alleviate many diseases and can be used for better human health.     

Reanalysis of the gene expression profile in chronic pancreatitis via bioinformatics methods

Background

Diagnosis at an early stage of chronic pancreatitis (CP) is challenging. It has been reported that microRNAs (miRNAs) are increasingly found and applied as targets for the diagnosis and treatment of various cancers. However, to the best of our knowledge, few published papers have described the role of miRNAs in the diagnosis of CP.

Method

We downloaded gene expression profile data from the Gene Expression Omnibus and identified differentially expressed genes (DEGs) between CP and normal samples of Harlan mice and Jackson Laboratory mice. Common DEGs were filtered out, and the semantic similarities of gene classes were calculated using the GOSemSim software package. The gene class with the highest functional consistency was selected, and then the Lists2Networks web-based system was used to analyse regulatory relationships between miRNAs and gene classes. The functional enrichment of the gene classes was assessed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway annotation terms.

Results

A total of 405 common upregulated DEGs and 7 common downregulated DEGs were extracted from the two kinds of mice. Gene cluster D was selected from the common upregulated DEGs because it had the highest semantic similarity. miRNA 124a (miR-124a) was found to have a significant regulatory relationship with cluster D, and DEGs such as CHSY1 and ABCC4 were found to be regulated by miR-124a. The GO term of response to DNA damage stimulus and the pathway of Escherichia coli infection were significantly enriched in cluster D.

Conclusion

DNA damage and E. coli infection might play important roles in CP pathogenesis. In addition, miR-124a might be a potential target for the diagnosis and treatment of CP.     

Identification of the major allergen of Macrobrachium rosenbergii (giant freshwater prawn)

Objective

To characterize the major allergens of Macrobrachium rosenbergii (giant freshwater prawn).

Methods

Raw and cooked extracts of the giant freshwater prawn were prepared. The IgE reactivity pattern was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting technique with the sera of 20 skin prick test (SPT) positive patients. The major allergen identified was then characterized using the proteomics approach involving a combination of two-dimensional (2-DE) electrophoresis, mass spectrometry and bioinformatics tools.

Results

SDS-PAGE of the raw extract showed 23 protein bands (15–250 kDa) but those ranging from 40 to 100 kDa were not found in the cooked extract. From immunoblotting experiments, raw and cooked extracts demonstrated 11 and 5 IgE-binding proteins, respectively, with a molecular mass ranging from 15 to 155 kDa. A heat-resistant 36 kDa protein was identified as the major allergen of both extracts. In addition, a 42 kDa heat-sensitive protein was shown to be a major allergen of the raw extract. The 2-DE gel fractionated the prawn proteins to more than 50 different protein spots. Of these, 10 spots showed specific IgE reactivity with patients'' sera. Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis led to identification of 2 important allergens, tropomyosin and arginine kinase.

Conclusions

It can be concluded that the availability of such allergens would help in component-based diagnosis and therapy of prawn allergies.     

Kikuchi-Fugimoto Disease (Cervical Subacute Necrotising Lymphadenitis): An important benign disease often masquerading as lymphoma

Objectives

We describe a rare cause of posterior triangle cervical lymphadenopathy in a third decade female, outline the clinical and histopathological features and discuss excision biopsy as the investigation of choice in this age group, with lymphoma as the diagnosis of exclusion.

Case report

A thirty-four year old female was referred to our Head and Neck clinic with a one-month history of left posterior triangle lymphadenopathy. She reported no other symptoms and haematological investigations were normal. She was “Red Flagged” as a possible lymphoma. Excision biopsy revealed extensive histiocytic necrotising lymphadenitis providing a diagnosis of Kikuchi-Fujimoto disease.

Conclusions

Persistent posterior triangle lymphadenopathy in the 16-40 year old age group warrants “Red Flag” referral to rule out serious pathology such as HIV, metastatic cancer or lymphoma. When the ENT examination and haematological work up is negative, we advocate proceeding straight to excision biopsy as the quickest way to obtain a diagnosis, which sometimes comes up with the unexpected as in this rare case of Kikuchi-Fujimoto disease.     

Cancer risk in HIV-infected individuals on HAART is largely attributed to oncogenic infections and state of immunocompetence

Objectives

To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy.

Methods

Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk.

Results

1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin''s disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p < 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p < 0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p < 0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer.

Conclusions

HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.     

Analytical characterization and structure elucidation of metabolites from Aspergillus ochraceus MP2 fungi

Objective

To isolate and characterize the bioactive secondary metabolites from Aspergillus ochraceus (A. ochraceus) MP2 fungi.

Methods

The anti bacterial activity of marine sponge derived fungi A. ochraceus MP2 was thoroughly investigated against antagonistic human pathogens. The optimum inhibitory concentration of the fungi in the elite solvent was also determined. The promising extracts that showed good antimicrobial activity were subjected to further analytical separation to get individual distinct metabolites and the eluants were further identified by GC MS instrumental analysis. The molecular characterization of the elite fungal strains were done by isolating their genomic DNA and amplify the internal transcribed spacer (ITS) region of 5.8s rRNA using specific ITS primer. The novelty of the strain was proved by homology search tools and elite sequences was submitted to GENBANK.

Results

Three bioactive compounds were characterized to reveal their identity, chemical formula and structure. The first elutant was identified asα- Campholene aldehyde with chemical formula C₁₀ H₁₆ O and molecular weight 152 Da. The second elutant was identified as Lucenin-2 and chemical formula C₂₇ H₃₀ O₁₆ and molecular weight 610 Da. The third elutant was identified as 6-Ethyloct- 3-yl- 2- ethylhexyl ester with Chemical formula C₂₆ H₄₂ O₄ with molecular weight 418 Da.

Conclusions

The isolated compounds showed significant antimicrobial activity against potential human pathogens. Microbial secondary metabolites represent a large source of compounds endowed with ingenious structures and potent biological activities.     

Research and applications: N-gram support vector machines for scalable procedure and diagnosis classification,with applications to clinical free text data from the intensive care unit

Background

Existing risk adjustment models for intensive care unit (ICU) outcomes rely on manual abstraction of patient-level predictors from medical charts. Developing an automated method for abstracting these data from free text might reduce cost and data collection times.

Objective

To develop a support vector machine (SVM) classifier capable of identifying a range of procedures and diagnoses in ICU clinical notes for use in risk adjustment.

Materials and methods

We selected notes from 2001–2008 for 4191 neonatal ICU (NICU) and 2198 adult ICU patients from the MIMIC-II database from the Beth Israel Deaconess Medical Center. Using these notes, we developed an implementation of the SVM classifier to identify procedures (mechanical ventilation and phototherapy in NICU notes) and diagnoses (jaundice in NICU and intracranial hemorrhage (ICH) in adult ICU). On the jaundice classification task, we also compared classifier performance using n-gram features to unigrams with application of a negation algorithm (NegEx).

Results

Our classifier accurately identified mechanical ventilation (accuracy=0.982, F₁=0.954) and phototherapy use (accuracy=0.940, F₁=0.912), as well as jaundice (accuracy=0.898, F₁=0.884) and ICH diagnoses (accuracy=0.938, F₁=0.943). Including bigram features improved performance on the jaundice (accuracy=0.898 vs 0.865) and ICH (0.938 vs 0.927) tasks, and outperformed NegEx-derived unigram features (accuracy=0.898 vs 0.863) on the jaundice task.

Discussion

Overall, a classifier using n-gram support vectors displayed excellent performance characteristics. The classifier generalizes to diverse patient populations, diagnoses, and procedures.

Conclusions

SVM-based classifiers can accurately identify procedure status and diagnoses among ICU patients, and including n-gram features improves performance, compared to existing methods.