Toward creation of a cancer drug toxicity knowledge base: automatically extracting cancer drug–side effect relationships from the literature

Objective

A comprehensive and machine-understandable cancer drug–side effect (drug–SE) relationship knowledge base is important for in silico cancer drug target discovery, drug repurposing, and toxicity predication, and for personalized risk–benefit decisions by cancer patients. While US Food and Drug Administration (FDA) drug labels capture well-known cancer drug SE information, much cancer drug SE knowledge remains buried the published biomedical literature. We present a relationship extraction approach to extract cancer drug–SE pairs from the literature.

Data and methods

We used 21 354 075 MEDLINE records as the text corpus. We extracted drug–SE co-occurrence pairs using a cancer drug lexicon and a clean SE lexicon that we created. We then developed two filtering approaches to remove drug–disease treatment pairs and subsequently a ranking scheme to further prioritize filtered pairs. Finally, we analyzed relationships among SEs, gene targets, and indications.

Results

We extracted 56 602 cancer drug–SE pairs. The filtering algorithms improved the precision of extracted pairs from 0.252 at baseline to 0.426, representing a 69% improvement in precision with no decrease in recall. The ranking algorithm further prioritized filtered pairs and achieved a precision of 0.778 for top-ranked pairs. We showed that cancer drugs that share SEs tend to have overlapping gene targets and overlapping indications.

Conclusions

The relationship extraction approach is effective in extracting many cancer drug–SE pairs from the literature. This unique knowledge base, when combined with existing cancer drug SE knowledge, can facilitate drug target discovery, drug repurposing, and toxicity prediction.     

Enhancing the evidence base for clinical psychiatry: are practice surveys a useful tool?

Clinical practice guidelines for psychiatry are now being developed, but important deficits in the evidence base are apparent. For many of the new treatments, clinical decisions can be idiosyncratic or based on limited knowledge. There is a need not only to perform properly constructed trials, but also to make immediate use of less rigorous forms of evidence, such as clinical practice surveys. An example is a recent survey of psychiatrists' use of antidepressant drugs. Such surveys are now part of a wider movement towards a more coordinated system of practice-based outcome assessment.     

Diagnosis of a case of thymus area lymphoma

This was a rare case,in which clinical manifestation was a thymus area tumor accompanied by proteinuria,kidney dysfunction and kidney enlargement.Tumor biopsy and bone marrow examination failed to clarify its diagnosis.Renal biopsy revealed diffuse infiltra- tion by atypical lymphoid cells in renal interstitium.Immunoperoxidase studies demonstrated this case was non-Hodgkin's lymphoma (NHL)of the B cell type through the renal biopsy.     

Primary care support for youth mental health: a preliminary evidence base for Ireland’s Mid-West

Background

Mental and substance use disorders are leading causes of morbidity. Prevention/treatment amongst young people are global health priorities. International data have highlighted primary care and general practice as important in addressing these.

Aims

Survey of 128 physicians (GPs) in Ireland’s Mid-West (Counties Limerick, Clare, North Tipperary) to document the spectrum of youth mental health problems, describe strategies adopted by GPs in dealing with these, identify barriers (perceived by GPs) to effective care of young mental health patients and collate GP proposals for improved care of this cohort.

Methods

Self-administered questionnaire on physician and practice demographics, case management and barriers to care in youth mental health.

Results

Thirty-nine GPs (31 %) responded. Mental health and family conflict represented the most frequent reasons why young people attended GPs. Depression, anxiety, family conflict, suicidal thoughts/behaviour, and attention deficit hyperactivity disorder (ADHD) were the most common issues followed by substance abuse and antisocial behaviours. GP referral practices for young people with mental/substance use disorders varied, with distinctions between actual and preferred management due to insufficient access to dedicated youth services and training. GPs stated need for improved access to existing services (i.e., Psychiatry, counseling/psychology, social/educational interventions). A number of GPs surveyed were located, or provided care, in Limerick’s ‘Regeneration Areas’. Young people in these areas predominantly attended GPs due to mental/substance use issues and antenatal care, rather than acute or general medical problems.

Conclusions

GPs play an important role in meeting youth mental health needs in this region and, in particular, in economically deprived urban areas.     

Primary Report of a New Strain of Hemolytic Gemella

A new strain of hemolytic gemella(HG)was Isolated from woundexudates,pleural fluid and sputum of 12 patients.It is similar to thecocci gemella hemolysans in form,staining and growth,but is differentfrom them in respect of the morphological arrangement,mode of repro-duction,and contour of colony.It is aerobic,quick-hemolytic and auto-Iytic.Our study indicates that this strain formerly regarded as a usualbacterium present in the respiratory system is actually a new variant.On the basis of light and electron microscopic observation,identificationof bacteria,determination of antibodies and animal inoculation,a singlepure species of bacteria was obtained from purulent exudate culture.Clinical events proved that this organism is a pathogenic variant strainof hemolytic gemella.     

Oxygenation of Liver Transplants as a Predictor of Success

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Are low cholesterol values associated with excess mortality?

The relation between cholesterol concentration and mortality was studied prospectively over 17 years in 630 New Zealand Maoris aged 25-74. The dead or alive state of each person was determined in 1981. The causes of death were divided into three categories: cancer, cardiovascular disease, and "other." Using univariate and both linear and non-linear multivariate methods of analysis for survivorship data, significant inverse relations with serum cholesterol were found for total mortality in women, for mortality from cancer in men and women, and for other causes of mortality in both men and women. The inverse and non-linear association with total mortality in women remained significant when deaths in the first five years of follow up were excluded. This suggests that the association was not explained by undetected illness causing low cholesterol concentrations at the time of initial examination.     

A complication of becoming a centenarian

About three years ago a blind patient of mine reached his lOOth birthday. He held an open house at his home, a fisherman＇ s cottage perched high up overlooking the whole of Swansea bay. I was invited, as were many others, and even the mayor called in.     

Action of autonomic drugs on the in vivo bladder base and proximal urethra in dog.

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Effect of a novel dietary supplement on pH levels of healthy volunteers： a pilot study

OBJECTIVE： To examine the effects of a greens alkalizing dietary supplement on urinary pH levels in individuals with lower-than-average pH levels. METHODS： The present study investigated the effects of an alkalizing formula （Reserveage Wholeganic GreensTM） on four individuals who had average urinary pH levels below 6.0 for three consecutive days. Following the three-day, baseline period, participants received Reserveage Wholeganic GreensTM for four consecutive days and were instructed to continue to measure their urine pH levels. Paired samples t-tests were used to examine pH levels before and after a four-day treatment period with Reserveage Wholeganic GreensTM. RESULTS： Compared to baseline, mean urine pH levels in all volunteers were significantly higher following the supplementation with Reserveage Wholeganic GreensTM （5.89 ±0.20 vs 5.56 ± 0.23; P〈0.01）. Participants＇ pH levels were also significantly higher than baseline on days 5, 6, and 7 of the treatment period （P 〈 0.05）. Noteworthy, on day 7, participants＇ mean pH levels were significantly higher than at the beginning of the treatment period （6.03 ± 0.15 at day 7 vs 5.65 ± 0.24 at day 4; P 〈 0.01）. CONCLUSION： The findings of this study suggest that supplementation with Reserveage Wholeganic GreensTM has an alkalizing effect on the body and can increase the urine pH levels in individuals with lower-than-average pH levels.     

Aspergilosis of the larynx:a report of 8 cases

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Imaging manifestations of von Hippel-Lindau disease: a report of 3 casesImaging manifestations of von Hippel-Lindau disease: a report of 3 cases

Von Hippel-Lindau (VHL) disease is an autosomal dominant here ditary familial neoplasm syndrome characte rized by development of a variety of benign and malignant tumors in multiple organ systems,such as the brain,kidney,pancreas,adrenalgland,and epididymis,with aprev a lence of one in 39000- 53000.1 4 Hallmarks of the condition in clude retinal angiomas,hem angioblastomas of the cerebellum and the spinal cord,renal cell carcinoma and cysts,and pheochrom ocytomas.In this article,we report imaging findings in three cases of VHLdisease.     

Fast estimation of Michaelis-Menten constant of arylesterase with a pair of medi-um concentrations of substrate

Objective: To investigate the reliability for fast estimation of Michaelis-Menten constant (Km) with calibra-ted specific activity at only two medium concentrations of substrate by both simulation and experimentation with aryles-terase (ArE)as model. Methods: Initial rates were simulated by randomly inserting uniform absolute error, and the experimental initial rates of ArE were determined by measuring the increaser of product absorbance. Calibrated specific activities at two substrate concentrations were obtained by regression analysis, and Km was calculated according to Michaelis-Menten equation. Results: By simulation with calibrated specific activities at two medium substrate concen-trations, Km could be calculated according to Michaelis-Menten equation with reasonable precision and accuracy. By experimentation with substrates of 2-naphthyl acetate, phenyl acetate, and p-nitrophenyl acetate, there were no differ-ences between the mean and SD of Km of ArE for either substrate by this linear kinetic method and the Lineweaver-Burk plot. Conclusion: This linear kinetic method was reliable for fast estimation of the Km of some specified enzyme on its substrate of lower solubility or lower sensitivity for quantification by common methods.     

Verruciform xanthoma of the penis:report of a case

Verruciformxanthoma ,arareandbenignlesionthatwasfirstdescribedbyShafer1　in 1971,occursmainlyintheoralmucosa ,butextra oralinvolvementincludesthevulva,2 ,3　scrotum ,4 ,5　penis ,6 15　analregion16 　andextremities 17,18　Withsessileorpedunculatedgrowththislesionissmall,asymptomatic ,yellow brownorred orangeincolor,andflat Clinically ,verruciformxanthomaislikelytobemisdiagnosedaspapillomasandoccasionallyasverrucousorsquamouscellcarcinoma Ithasabenigncourseandgoodprognosis Wereportacaseofve…     

Investigation of hHB genes in a predigree of congenital monilethrix

Objective： To investigate the gene polymorphism in a pedigree of congenital monilethrix. Methods： Genomic DNA of affected members, the normal members of the pedigree and 50 unrelated normal members who came from different regions were extracted with a whole blood genomic DNA extraction kit and used as a template for the polymerase chain reaction （PCR）-mediated amplification of hHB1 and hHB6 genes. Results： In the pedigree, DNA analysis of patients and normal persons revealed C（447th） in exonl of hHB1 gene and the 52th codon was CCA encoding arginine. But it was a heteropeak of O or C in 50 unrelated normal members, which encodes glycine or arginine. It showed that this change was a single nucleotide polymorphisms （SNP）. Conclusion： A genetic heterogeneity of monilethrix exists in Chinese population. SNP which can result in the change of amino acid sequence is found in a pedigree of congenital monilethrix, and a genetic heterogeneity of monilethrix existed in Chinese population.     

Can an information booklet on an ethnic minority increase the knowledge base of junior doctors?

Many doctors encounter people of different cultural backgrounds for the first time as patients. In Leicester a significant proportion of the area's population comes from a Gujarati and Hindu background. In an attempt to better inform junior doctors about the views and beliefs of their patients, a group of clinicians and administrators developed an information booklet about the beliefs and practices of people from this community. The impact of this booklet on a group of 54 junior doctors' knowledge was investigated over a period of one month. Such an information booklet was found to significantly increase awareness of the cultural background of patients from a minority community and this knowledge was maintained for at least one month after distribution. The study did not investigate impact on attitudes.     

Reappraisal of diagnostic significance of a hepatoma-specific band of serum gamma-glutamyl transferase.

The hepatoma-specific band of serum gamma-glutamyl transferase II (GGT II) and other three markers were evaluated in 77 patients with primary hepatocellular carcinoma (PHC). The positive rate of GGT II (87%) was much higher than that of the increased alpha-fetoprotein (AFP greater than or equal to 400 ng/ml, 54.5%), the increased alpha-1-antitrypsin (AAT greater than or equal to 400 mg/dl, 64.9%) and alkaline phosphatase isoenzyme I (ALP I, 13.0%). In patients with AFP less than 400 ng/ml, the positive rate of GGT II was 95.2%, higher than that of ALP I (22.8%) and AAT (60.0%). The positive rate of GGT II was positively correlated to the volume of PHC (r = 0.324, P less than 0.05), but even in patients with small PHC (less than or equal to 65 cm3), the positive rate of GGT II (78.6%) was higher than that of AFP (50.0%) and AAT (28.6%). The ALP I positivity was only seen in patients with larger PHC. Follow-up study showed that GGT II, like AFP, might occur before liver tumor could be detected by B-mode ultrasonography and computerized tomography. Therefore, GGT II is a valuable marker of PHC, especially in patients whose AFP was negative or slightly increased; GGT II may be useful for relatively early diagnosis of PHC.