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Evidence-based dietary information represented as unstructured text is a crucial information that needs to be accessed in order to help dietitians follow the new knowledge arrives daily with newly published scientific reports. Different named-entity recognition (NER) methods have been introduced previously to extract useful information from the biomedical literature. They are focused on, for example extracting gene mentions, proteins mentions, relationships between genes and proteins, chemical concepts and relationships between drugs and diseases. In this paper, we present a novel NER method, called drNER, for knowledge extraction of evidence-based dietary information. To the best of our knowledge this is the first attempt at extracting dietary concepts. DrNER is a rule-based NER that consists of two phases. The first one involves the detection and determination of the entities mention, and the second one involves the selection and extraction of the entities. We evaluate the method by using text corpora from heterogeneous sources, including text from several scientifically validated web sites and text from scientific publications. Evaluation of the method showed that drNER gives good results and can be used for knowledge extraction of evidence-based dietary recommendations.

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by recurrent life-threatening oedemas and/or abdominal pain and caused by mutations affecting the C1 inhibitor gene, SERPING1. We sought to investigate the spectrum of SERPING1 mutations in Serbia and the possible genotype-phenotype association. C1-INH-HAE was diagnosed on the basis of clinical and laboratory criteria in 40 patients from 27 families; four were asymptomatic. Mutational analysis of the SERPING1 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in SERPING1 were identified in all patients. In C1-INH-HAE type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations (c.300C>T and c.1184_1185insTA) are reported here for the first time. All C1-INH-HAE type II patients from three families harboured the same substitution (c.1396C>T). Based on the type of mutation identified in the SERPING1 gene, patients were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at Arg444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) oedema, and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. Furthermore, it appears that mutations with a clear effect on C1-INH function might be responsible for a more severe disease phenotype.

BACKGROUND: We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. METHODS: In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. RESULTS: We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. CONCLUSIONS: Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific.

Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by swelling of the face, lips, tongue, larynx, genitalia, or extremities, with abdominal pain caused by intra-abdominal edema. HAE is caused by mutations affecting the C1 inhibitor gene, SERPING1, resulting in low levels of C1 inhibitor (Type I HAE) or normal levels of ineffective C1 inhibitor (Type II HAE). A nationwide survey identified nine unrelated families with HAE in Slovenia, among whom 17 individuals from eight families were recruited for genetic analyses. A diagnosis of HAE was established in the presence of clinical and laboratory criteria (low C1 inhibitor antigenic levels and/or function), followed up by a positive family history. Genetic studies were carried out using PCR and sequencing to detect SERPING1 mutations in promoter, noncoding exon 1, the 7 coding exons, and exon-intron boundaries. Multiplex ligation-dependent probe amplification was performed in order to search for large deletions/duplications in SERPING1 gene. A mutation responsible for HAE was identified in patients from seven families with the disease. In HAE type I families, one previously reported substitution (Gln67Stop, c.265C>T) and four novel mutations were identified. The new mutations included two missense substitutions, Ser128Phe (c.449C>T), and Glu429Lys (c.1351G>A), together with two frameshift mutations, indel (c.49delGinsTT) and deletion (c.593_594delCT). Both families with HAE type II harbored the two well-known substitutions affecting the arginyl residue at the reactive center in exon 8, Arg444Cys (c.1396C>T) and Arg444His (c.1397G>A), respectively. In one patient only the homozygous variant g.566T>C (c.-21T>C) was identified. Our study identified four novel mutations in the Slovenian HAE population, highlighting the heterogeneity of mutations in the SERPING1 gene causing C1 inhibitor deficiency and HAE. In a single patient with HAE a homozygous variant g.566T>C (c.-21T>C) might be responsible for the disease.

Angiogenesis is a critical event in the development, progression, and spread of various human cancers, including lung cancer. Molecular mechanisms that underlie the complex regulation of angiogenic processes are poorly understood. However, an increasing body of evidence indicates miRNAs as important regulators of tumor angiogenesis. Forceps biopsies were collected from tumor tissue, surrounding tissue, and non-tumor tissue from 50 NSCLC patients. Lung tissue samples from individuals with no clinical evidence of a cancerous disease served as controls. Immunohistochemical staining for Factor VIII was used to evaluate microvessel density (MVD). TaqMan® primer-probe sets were used in quantitative real-time RT-PCR reactions to determine expression levels of let-7b, miR-126, miR-9, and miR-19a. We demonstrated significantly higher MVD and decreased expression levels of let-7b and miR-126 in tumor tissue and surrounding tissue in comparison to corresponding non-tumor tissue or lung tissue from the control group. In addition, no differences in MVD and expression levels of both miRNAs between tumor tissue and surrounding tissue from NSCLC patients were observed. Low expression of both miRNAs correlated with high MVD and worse progression-free survival and overall survival. These observations strongly suggest similar molecular alternations within tumor tissue and surrounding tissue that comprise a specific microenvironment. Low expression of let-7b and miR-126 seems to have a possible anti-angiogenic role in lung tumor tissue and significantly correlates with worse survival outcomes for lung cancer patients. Moreover, the regulation of let-7b and miR-126 expression could have therapeutic potential because it could reduce tumor angiogenesis and therefore suppress tumor growth in lung cancer patients.

BackgroundAllergy to bee and wasp venom can lead to life-threatening systemic reactions. The identification of the culprit species is important for allergen-specific immunotherapy.ObjectivesTo determine a panel of recombinant bee and wasp allergens which is suitable for the identification of bee or wasp as culprit allergen sources and to search for molecular surrogates of clinical severity of sting reactions.MethodsSera from eighty-seven patients with a detailed documentation of their severity of sting reaction (Mueller grade) and who had been subjected to titrated skin testing with bee and wasp venom were analyzed for bee and wasp-specific IgE levels by ImmunoCAPTM. IgE-reactivity testing was performed using a comprehensive panel of recombinant bee and wasp venom allergens (rApi m 1, 2, 3, 4, 5 and 10; rVes v 1 and 5) by ISAC chip technology, ImmunoCAP and ELISA. IgG4 antibodies to rApi m 1 and rVes v 5 were determined by ELISA and IgE/IgG4 ratios were calculated. Results from skin testing, IgE serology and IgE/IgG4 ratios were compared with severity of sting reactions.ResultsThe panel of rApi m 1, rApi m 10, rVes v 1 and rVes v 5 allowed identification of the culprit venom in all but two of the 87 patients with good agreement to skin testing. Severities of sting reactions were not associated with results obtained by skin testing, venom-specific IgE levels or molecular diagnosis. Severe sting reactions were observed in patients showing < 1 ISU and < 2kUA/L of IgE to Api m 1 and/or Ves v 5.ConclusionWe identified a minimal panel of recombinant bee and wasp allergens for molecular diagnosis which may permit identification of bee and/or wasp as culprit insect in venom-sensitized subjects. The severity of sting reactions was not associated with parameters obtained by molecular diagnosis.