Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Molecular roles of short chain fatty acids in colorectal cancer

Colorectal cancer is the third most common malignancy in the western world in respect to incidence and mortality rates. In Australia, colorectal cancer was the second most common registrable cancer in 2001 with 12,844 new cases reported and since 1991 both male and female incidence rates have increased each year by an average of 0.3% and 0.1% respectively. Despite advances in both surgical resection technique, and adjuvant and neo-adjuvant chemo-radiotherapy, unless the cancer is detected at a very early stage, long term and disease-free survival rates are less than 100%. Prevention is the key to achieving long term survival.\ud \ud Low fibre diet is considered to be one of many possible causes of colorectal cancer. It has been suggested that high dietary fibre intake reduces the risk of colorectal cancer by increasing stool bulk and reducing transit time, thus minimising exposure of colorectal mucosa to potential carcinogens, while also altering microbial composition and reducing intraluminal pressure. With advances in molecular biology, the focus of research has shifted from the protective effects of a high fibre diet to the study of short chain fatty acids.\ud \ud Butyrate acid has been implicated as potentially the most significant short chain fatty acid in protecting the colorectal mucosa against colorectal cancer. Butyrate is a product of the bacterial fermentation of undigested dietary fibre in the lumen of the colon and rectum. It is the ligand to the short chain fatty acid receptors GPR43 and GPR41. At the cellular level, butyrate induces apoptosis by inhibition of histone deacetylase activity and induction of p21ᵂᵃᶠ¹/ᶜⁱᵖ¹ expression.\ud \ud The study aims to assess by immunohistochemistry and real-time RT-PCR, the expression of GPR43 and GPR41 in human colorectal mucosa and tumours, and the effects of butyrate on GPR43 and GPR41 in colorectal cancer cell lines. Immunohistochemical staining of paired, same subject normal colorectal mucosa and tumours suggested a significant down regulation of GPR43 and GPR41 in tumours. Butyrate reduced the GPR43 expression across three concentrations in HT-29. In summary, while more research is needed, GPR43 and GPR41 may play a role in mediating the apoptotic effects of butyrate

BRAF mutation: Current and future clinical pathological applications in colorectal carcinoma

The aims are to review the relevance of the BRAF mutations in the clinical settings of colorectal carcinoma. All the literature concerning BRAF mutations and colorectal carcinoma published in PubMed from 2010 to 2018 was reviewed. Multiple variants of BRAF mutations exist in colorectal cancer, the most common type being V600E. The mutation is found in 5 to 15% of colorectal carcinomas and is less common in Asian populations. BRAF mutations are linked with older age, female gender, cigarette smoking and are more common in the right (proximal) portion of the large intestine. BRAF mutations are associated with carcinomas of high histological grade and advanced cancer stages. Often BRAF mutated carcinomas demonstrate adverse histological features such as lymphovascular invasion, perineural invasion, tumour budding and lymph node metastases. BRAF mutations are found in serrated polyposis syndrome and have a negative correlation with hereditary nonpolyposis colorectal cancer (HNPCC). An array of methods of detection of BRAF mutation in colorectal carcinoma are available, such as immunohistochemistry and next generation sequencing, etc. Combinatorial approaches involving anti-BRAF therapies targeting both MAPK signalling as well as the PI3K/mTOR pathway could be a new approach for treatment of metastatic colorectal carcinoma. To conclude, BRAF mutation is important in the pathogenesis of colorectal cancer. Further research on the detection method as well as its role in target therapy will help to improve the management of patients with colorectal cance

Subcutaneous neostigmine appears safe and effective for acute colonic pseudo‐obstruction (Ogilvie's syndrome)

Intravenous neostigmine is a well-established treatment for acute colonic pseudo-obstruction (ACPO). Its use is hampered by the perceived requirement for continuous cardiac monitoring, and patients are often transferred to high-dependency units for close observation during treatment. Subcutaneous neostigmine has the potential to minimize adverse cardiovascular effects while maintaining efficacy. This study aims to assess the safety of subcutaneous neostigmine on ward inpatients with ACPO monitored with standard nursing care.This is a retrospective case series of 30 patients with ACPO who were treated with subcutaneous neostigmine between August 2008 and October 2012. Data were collected prospectively. All patients were diagnosed using clinical examination and radiology and were assessed for contraindications to neostigmine. Patients were treated on regular wards and monitored with standard nursing observations. The main outcomes were time to flatus and bowels working and complications.No serious complications such as clinically evident bradycardia were encountered. Ninety-three percent of patients had clinically successful resolution of ACPO. Two patients (7%) developed caecal tenderness and proceeded to colonoscopic decompression, which was successful in both instances.Subcutaneous neostigmine appears to be safe for the treatment of ACPO. No clinically evident serious adverse events occurred, meaning continuous cardiac monitoring as a routine may not be necessary. In our cohort, we achieved similar success rates compared with reported rates using intravenous neostigmine

JK1 (FAM134B) gene and colorectal cancer: A pilot study on the gene copy number alterations and correlations with clinicopathological parameters

AIMS The aims of the study are to characterize changes in JK-1 (FAM134B) at the DNA level in colorectal adenocarcinoma and adenoma and exploring the possible correlations with clinical and pathological features. METHOD JK-1 gene DNA copy number changes were studied in 211 colorectal carcinomas, 32 colorectal adenoma and 20 colorectal non-cancer colorectal tissue samples by real-time quantitative polymerase chain reaction. The results were correlated with clinical and pathological parameters. RESULTS Colorectal adenomas were more likely to be amplified than deleted with regard to JK-1 (FAM134B) DNA copy number change. The copy number level of JK-1 (FAM134B) DNA in colorectal adenocarcinomas was significantly lower in comparison to colorectal adenomas. Changes in JK-1 (FAM134B) DNA copy number were associated with histological subtypes, and cancer stage. Lower copy numbers were associated with higher tumor stage, lymph node stage and overall pathological stage of cancer. Conversely, higher DNA copy numbers were detected more often in the mucinous adenocarcinoma. CONCLUSIONS This is the first study showing significant correlations of the JK-1 (FAM134B) gene copy number alterations with clinical and pathological features in a large cohort of pre-invasive and invasive colorectal malignancies. The changes in DNA copy number associated with progression of colorectal malignancies reflect that JK-1 (FAM134B) gene could play a role in controlling some steps in development of the invasive phenotypes

Deregulation of miR-126 expression in colorectal cancer pathogenesis and its clinical significance

In this study, we investigated the expression profiles and clinicopathological significance of miR-126 in large cohort of patients with colorectal cancers as well the cellular repercussions of miR-126 in colon cancer cells along with its targets in-vitro. Down regulation of miR-126 expression was associated with histological subtypes, peri-neural tumour infiltration, microsatellite instability and pathological staging of colorectal cancers (p<0.05). Low miR-126 expression was also associated with poorer survival in patients with colorectal cancer. Analysis of matched tissues from the same patient revealed that approximately 70% of the tested patients had similar levels of expression of miR-126 in primary cancer and cancer metastases in both lymph node and distant metastases. In addition, induced overexpression of miR-126 showed reduced cell proliferation, increased apoptosis and decreased accumulation of cells in the G0-G1 phase of the colon cancer cells. Furthermore, SW480(+miR-126) cells showed reduced BCL-2 and increased P53 protein expression. To conclude, deregulation of miR-126 in colorectal cancer at the tissue and cellular levels as well as its correlation with various clinicopathological parameters confirm the cancer suppressive role of miR-126 in colorectal cancer

Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma

The aim of the present study was to isolate and investigate the genetic heterogeneities in single circulating tumour cells (CTCs) from patients with colorectal carcinoma (CRC). Twenty-eight single CTCs were collected from eight patients with CRC using a negative immunomagnetic enrichment method. After validation with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression in 3 colon cancer cell lines, a panel of 19 genes were used to analyse the single CTCs (n = 28), primary colorectal carcinoma tissues (n = 8) and colon carcinoma cells (n = 6) using real-time qPCR. Genetic heterogeneities were assessed by comparing gene expression profiles of single CTCs from the different patients and in the same patient, respectively. Genetic profiling of the single CTCs showed extensive heterogeneities of the selected genes among the CTCs. Hierarchical clustering analyses exhibited two clusters of CTCs with differentially expressed genes, which highlighted different modifications from the primary carcinomas. Further, the genetic heterogeneities were observed between different patients or in the same patient. Finally, AKT1 expression was significantly (p = 0.0129) higher in single CTCs from CRC of advanced pathological stages (III or IV) CRC than in CTCs from CRC of early stages (I or II). Our findings suggest that single-cell genetic analysis can monitor the genetic heterogeneities and guide the personalised therapeutic targets in clinical sectors

Expression pattern of miR-451 and its target MIF (macrophage migration inhibitory factor) in colorectal cancer

Aims To investigate the expression pattern of microRNA-451 (miR-451) in patients with colorectal carcinoma and correlate with the expression of its target gene MIF (macrophage migration inhibitory factor). Methods Matched cancer and non-cancer fresh frozen tissues were prospectively collected from 70 patients (35 men and 35 women) who underwent resection of colorectal adenocarcinoma. These tissues collected were extracted for miR and complementary DNA conversion. Then, miR-451 expressions in these tissues were measured by quantitative real-time PCR. The expression was correlated with clinical and pathological parameters of these patients. In addition, paraffin blocks of 10 colorectal carcinomas with lowest expression of miR-451 were used for the study of MIF protein expression by immunohistochemistry. Results miR-451 was downregulated in majority of the colorectal cancer tissues when compared with their matched normal tissues (84.3%, n=59/70). Downregulation of miR-451 correlates significantly with presence of coexisting adenoma (91.4%, p=0.025). In addition, persistence of cancer or cancer recurrence after surgery showed significant correlation with downregulation of miR-451 (80% vs 0%; p=0.028). There is no significant correlation between miR-451 expression and age, gender of the patients as well as size, grades, pathological stages, presence of lymphovascular permeation, perineural invasion and microsatellite instability status of the colorectal carcinoma (p>0.05). Majority of the cases (80%) with low expression of miR-451 showed high levels of MIF protein expression confirming the inverse relationship between miR-451 and MIF expressions. Conclusions The results showed that miR-451 could play a role in development and progression of colorectal cancer and likely by targeting MIF

Promoter hypermethylation inactivate tumour suppressor FAM134B and is associated with poor prognosis in colorectal cancer

The present study aims to examine promoter methylation status of FAM134B in a large cohort of patients with colorectal adenocarcinomas. The clinical significances and correlations of FAM134B promoter methylation with its expression are also analysed. Methylation-specific high-resolution melt-curve analysis followed by sequencing was used to identify FAM134B promoter methylation in colorectal adenomas (n=32), colorectal adenocarcinomas (n=164), matched adjacent non-neoplastic colorectal mucosae (n=83) and colon cancer cell lines (n=4). FAM134B expression was studied by real-time quantitative polymerase chain reaction, immunohistochemistry, and Western blots. FAM134B promoter methylation was more frequent in adenocarcinomas (52%; 85/164) when compared to that of adenomas (28%; 9/32) and non-neoplastic mucosae (35%; 29/83). Cancer cells exhibited higher methylation when compared to non-neoplastic cells. FAM134B promoter methylation was inversely correlated with low FAM134B copy number and mRNA/protein expressions, whereas in-vitro demethylation has restored FAM134B expression in colon cancer cells. FAM134B promoter methylation was associated with high histological grade (p = 0.025), presence of peri-neural infiltration (p = 0.012), lymphovascular invasion (p = 0.021), lymph node metastasis (p = 0.0001), distant metastasis (p = 0.0001) and advanced pathological stages (p = 0.0001). In addition, FAM134B promoter methylation correlated with cancer recurrence and poor survival rates of patients with colorectal adenocarcinomas. To conclude, FAM134B promoter methylation plays a key role in regulating FAM134B expression in-vitro and in-vivo, which in turn contributes to the prediction of the biological aggressiveness of colorectal adenocarcinomas. Furthermore, FAM134B methylation might act as a marker in predicting clinical prognosis in patients with colorectal adenocarcinomas. This article is protected by copyright. All rights reserved