Biomedical word sense disambiguation with ontologies and metadata: automation meets accuracy

Background  

Ontology term labels can be ambiguous and have multiple senses. While this is no problem for human annotators, it is a challenge to automated methods, which identify ontology terms in text. Classical approaches to word sense disambiguation use co-occurring words or terms. However, most treat ontologies as simple terminologies, without making use of the ontology structure or the semantic similarity between terms. Another useful source of information for disambiguation are metadata. Here, we systematically compare three approaches to word sense disambiguation, which use ontologies and metadata, respectively.     

The future in and of criticality assessments

In recent literature, the concept of criticality aspires to provide a multifaceted risk assessment of resource supply shortage. However, most existing methodologies for the criticality assessment of raw materials are restricted to a fixed temporal and spatial reference system. They provide a snapshot in time of the equilibrium between supply and demand/economic importance and do not account for temporal changes of their indicators. The static character of criticality assessments limits the use of criticality methodologies to short‐term policy making of raw materials. In the current paper, we argue for an enhancement of the criticality framework to account for three key dynamic characteristics, namely changes of social, technical, and economic features; consideration of the spatial dimension in site‐specific assessments; and impact of changing governance frameworks. We illustrate how these issues were addressed in studies outside of the field of criticality and identify the dynamic parameters that influence resource supply and demand based on a review of studies that belong to the general field of resource supply and demand. The parameters are grouped in seven categories: extraction, social, economic, technical, policy, market dynamics, and environmental. We explore how these parameters were considered in the reviewed studies and propose ways and specific examples of addressing the dynamic effects in the criticality indicators. Furthermore, we discuss the current work on future scenarios to provide reference points for indicator benchmarks. The insights and guidelines derived from the review and our recommendations for future research set the foundations for an enhanced dynamic and site‐specific criticality assessment framework.     

TRP channel–associated factors are a novel protein family that regulates TRPM8 trafficking and activity

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.     

Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab

Objective

In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses.

Design

Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0–1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy.

Results

Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects.

Conclusions

Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment.     

The in vivo preventive and therapeutic properties of curcumin in bile reflux‐related oncogenesis of the hypopharynx

Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre‐clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF‐κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF‐κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 μmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF‐κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile‐induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF‐κB, and shaping future translational development of effective targeted therapies using topical non‐pharmacologic inhibitors of NF‐κB.     

Cloning and characterization of the trout perforin

The pore-forming protein, perforin is one of the effectors of cell-mediated killing. A perforin cDNA clone was isolated from rainbow trout (Oncorhynchus mykiss) after screening of a spleen cDNA library. The full-length cDNA is 2070 bp in size, encoding for a polypeptide of 589 amino acids. The predicted amino acid sequence of the trout perforin is 64, 58 and 40% identical to those of Japanese flounder, zebrafish and human perforins, respectively. Although its membrane attack complex/perforin (MACPF) domain is conserved, trout perforin shows low homology to human and trout terminal complement components (C6, C7, C8 and C9), ranging from 19 to 26% identity. Expression analysis reveals that the trout perforin gene is expressed in the blood, brain, heart, kidney, intestine and spleen. Phylogenetic analysis of proteins which belong to the MACPF superfamily clusters the trout perforin in the same group with other known perforins.     

Body composition determinants of metabolic phenotypes of obesity in nonobese and obese postmenopausal women

Objective : Although obesity is typically associated with increased cardiovascular risk, a subset of obese individuals display a normal metabolic profile (“metabolically healthy obese,” MHO) and conversely, a subset of nonobese subjects present with obesity‐associated cardiometabolic abnormalities (“metabolically obese nonobese,” MONO). The aim of this cross‐sectional study was to identify the most important body composition determinants of metabolic phenotypes of obesity in nonobese and obese healthy postmenopausal women. Design and Methods : We studied a total of 150 postmenopausal women (age 54 ± 7 years, mean ± 1 SD). Based on a cardiometabolic risk score, nonobese (body mass index [BMI] ≤ 27) and obese women (BMI > 27) were classified into “metabolically healthy” and “unhealthy” phenotypes. Total and regional body composition was assessed with dual‐energy X‐ray absorptiometry (DXA). Results : In both obese and nonobese groups, the “unhealthy” phenotypes were characterized by frequent bodyweight fluctuations, higher biochemical markers of insulin resistance, hepatic steatosis and inflammation, and higher anthropometric and DXA‐derived indices of central adiposity, compared with “healthy” phenotypes. Indices of total adiposity, peripheral fat distribution and lean body mass were not significantly different between “healthy” and “unhealthy” phenotypes. Despite having increased fat mass, MHO women exhibited comparable cardiometabolic parameters with healthy nonobese, and better glucose and lipid levels than MONO. Two DXA‐derived indices, trunk‐to‐legs and abdominal‐to‐gluteofemoral fat ratio were the major independent determinants of the “unhealthy” phenotypes in our cohort. Conclusions : The “metabolically obese phenotype” is associated with bodyweight variability, multiple cardiometabolic abnormalities and an excess of central relative to peripheral fat in postmenopausal women. DXA‐derived centrality ratios can discriminate effectively between metabolic subtypes of obesity in menopause.