Tumor-infiltrating lymphocytes and breast cancer mortality in racially and ethnically diverse participants of the Northern California Breast Cancer Family Registry.

Stromal tumor-infiltrating lymphocyte (sTIL) enrichment in pretreatment breast tumors has been associated with superior response to neoadjuvant treatment and survival. In a population-based cohort, we studied sTIL-survival associations by race and ethnicity. We assessed associations of continuous sTIL scores and sTIL-enriched breast cancers (defined as percent lymphocytic infiltration of tumor stroma or cell nests at cutoffs of 30%, 50%, and 70%) with clinical and epidemiologic characteristics and conducted multivariable survival analyses. Although we identified no difference in sTIL score by race and ethnicity, higher continuous sTIL score was associated with lower breast cancer-specific mortality only among non-Hispanic White and Asian American but not African American and Hispanic women. This finding suggests that complex factors influence treatment response and survival, given that sTIL enrichment was not associated with a survival advantage among women from minoritized groups, who more often experience health disparities. Further study of patient selection for sTIL-guided treatment strategies is warranted.

CROssBAR: comprehensive resource of biomedical relations with knowledge graph representations.

Systemic analysis of available large-scale biological/biomedical data is critical for studying biological mechanisms, and developing novel and effective treatment approaches against diseases. However, different layers of the available data are produced using different technologies and scattered across individual computational resources without any explicit connections to each other, which hinders extensive and integrative multi-omics-based analysis. We aimed to address this issue by developing a new data integration/representation methodology and its application by constructing a biological data resource. CROssBAR is a comprehensive system that integrates large-scale biological/biomedical data from various resources and stores them in a NoSQL database. CROssBAR is enriched with the deep-learning-based prediction of relationships between numerous data entries, which is followed by the rigorous analysis of the enriched data to obtain biologically meaningful modules. These complex sets of entities and relationships are displayed to users via easy-to-interpret, interactive knowledge graphs within an open-access service. CROssBAR knowledge graphs incorporate relevant genes-proteins, molecular interactions, pathways, phenotypes, diseases, as well as known/predicted drugs and bioactive compounds, and they are constructed on-the-fly based on simple non-programmatic user queries. These intensely processed heterogeneous networks are expected to aid systems-level research, especially to infer biological mechanisms in relation to genes, proteins, their ligands, and diseases.

UniRule: a unified rule resource for automatic annotation in the UniProt Knowledgebase.

MOTIVATION: The number of protein records in the UniProt Knowledgebase (UniProtKB: https://www.uniprot.org) continues to grow rapidly as a result of genome sequencing and the prediction of protein-coding genes. Providing functional annotation for these proteins presents a significant and continuing challenge. RESULTS: In response to this challenge, UniProt has developed a method of annotation, known as UniRule, based on expertly curated rules, which integrates related systems (RuleBase, HAMAP, PIRSR, PIRNR) developed by the members of the UniProt consortium. UniRule uses protein family signatures from InterPro, combined with taxonomic and other constraints, to select sets of reviewed proteins which have common functional properties supported by experimental evidence. This annotation is propagated to unreviewed records in UniProtKB that meet the same selection criteria, most of which do not have (and are never likely to have) experimentally verified functional annotation. Release 2020_01 of UniProtKB contains 6496 UniRule rules which provide annotation for 53 million proteins, accounting for 30% of the 178 million records in UniProtKB. UniRule provides scalable enrichment of annotation in UniProtKB. AVAILABILITY AND IMPLEMENTATION: UniRule rules are integrated into UniProtKB and can be viewed at https://www.uniprot.org/unirule/. UniRule rules and the code required to run the rules, are publicly available for researchers who wish to annotate their own sequences. The implementation used to run the rules is known as UniFIRE and is available at https://gitlab.ebi.ac.uk/uniprot-public/unifire.

Effect of heating oils and fats in containers of different materials on their trans fatty acid content.

BACKGROUND: The nature of the container material and temperature employed for deep-frying can have an influence on the development of trans fatty acids (TFAs) in the fat used. The present study was undertaken to determine the effect of heating vegetable oils and partially hydrogenated vegetable fats with different initial TFA content in stainless steel, Hindalium (an aluminium alloy), cast iron and glass containers. Ground nut oil (oil 1), refined, bleached and deodorised (RBD) palmolein (oil 2) and two partially hydrogenated vegetable oils with low (fat 1) and high (fat 2) TFA content were uniformly heated at 175-185 °C over a period of 12 h. RESULTS: An increase in TFA content to 20 g kg⁻¹ was observed in oil 2 in the cast iron container, while a decrease in TFA content of 20-30 g kg⁻¹ was observed in fat 2 in all containers. The heating process of fats and oils also led to an increase in Butyro refractometer reading and colour values. CONCLUSION: This study showed that the TFA 18:1t content of oil 1, oil 2 and fat 1 increased with repeated or prolonged heating. The cast iron container showed the highest increase in TFA 18:1t for RBD palmolein (oil 2). The amount of linoleic acid trans isomers formed in the heating process was negligible. Fat 2 with high initial TFA content showed a decrease in TFA 18:1 and 18:2 on heating in all containers. Oils heated in glass and stainless steel containers showed less TFA 18:1t formation.

Influence of etoricoxib on anticonvulsant activity of phenytoin and diazepam in experimental seizure models in mice.

OBJECTIVES: Our aim was to investigate the effect of etoricoxib on the anticonvulsant activity of phenytoin and diazepam against seizure models in mice. In addition the acute adverse effect of etoricoxib was assessed with a chimney test. METHODS: The maximal seizure pattern was induced in mice by giving an alternating current of 50 mA for 0.2 s, while chemical seizures were induced by intraperitoneal injection of pentylenetetrazole at its CD97 dose (97% convulsive dose for the clonic phase). Test drug was administered 45 min before the electrical or chemical induction of seizures in combination with conventional antiepileptics. The ability of the test drug to reduce or abolish the extensor phase of maximal electroshock and clonic-type seizures in the chemical induction method was selected as anti-seizure criteria. KEY FINDINGS: Concurrent treatment with etoricoxib at an oral dose of 10 mg/kg reduced the anticonvulsant potency of phenytoin. The protective effects of diazepam against pentylenetetrazole-induced convulsions was significantly increased and the mortality rate was reduced by concurrent treatment with etoricoxib (10 mg/kg p.o.) when compared with diazepam groups. No neurotoxic effect was observed with etoricoxib (10 mg/kg p.o.) and it had no impact on motor coordination in the chimney test in mice. Etoricoxib applied at its highest dose (10 mg/kg) significantly enhanced the free plasma levels of diazepam whereas the free plasma levels of phenytoin were significantly reduced. CONCLUSIONS: The obtained results suggest that the preferential cyclooxygenase-2 inhibitor etoricoxib significantly reduced the anticonvulsant action of phenytoin and significantly increased the beneficial action of diazepam against maximal electroshock and pentylenetetrazole-induced convulsions in a mouse model.

Evaluation of SLS: APG mixed surfactant systems as carrier for solid dispersion.

The present investigation aims at studying the effect of mixed surfactant system of sodium lauryl sulphate (SLS) and alkyl polyglucosides (C(10)APG, C(12)APG and C(12/14)APG) on dissolution rate enhancement of poorly water soluble drug. Aceclofenac--a non-steroidal anti-inflammatory agent was used as a model drug as it has limited water solubility. The influence of the surfactant concentration in various blends on dissolution rate of Solid Dispersion (SD), prepared using solution method with ethanol as the solvent was studied and the advantage of mixed surfactant systems over the individual surfactants was illustrated by differences in the in-vitro dissolution profiles of SD. Physico chemical evaluation (critical micellar concentration, zeta potential and beta-parameter calculations) was carried out to study the mixed surfactant systems. Solid mixtures were characterized by Infrared spectroscopy (FT-IR); X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). It was seen that the dissolution rate of aceclofenac from SD increased with the increase in the APG proportion relative to SLS with the optimum ratio of 0.2 SLS:0.8 APG showing the best effect in all cases. Results obtained from physico-chemical evaluation (the decrease in the value of critical micelle concentration and higher negative value of beta-parameters) suggested the existence of synergism between surfactants blends. The observed results in the dissolution rate enhancement could be attributed to the drug--surfactant interactions as evident from FT-IR, SEM and XRD results.

Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer.

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.