Identifying protein subcellular localisation in scientific literature using bidirectional deep recurrent neural network

The increased diversity and scale of published biological data has to led to a growing appreciation for the applications of machine learning and statistical methodologies to gain new insights. Key to achieving this aim is solving the Relationship Extraction problem which specifies the semantic interaction between two or more biological entities in a published study. Here, we employed two deep neural network natural language processing (NLP) methods, namely: the continuous bag of words (CBOW), and the bi-directional long short-term memory (bi-LSTM). These methods were employed to predict relations between entities that describe protein subcellular localisation in plants. We applied our system to 1700 published Arabidopsis protein subcellular studies from the SUBA manually curated dataset. The system combines pre-processing of full-text articles in a machine-readable format with relevant sentence extraction for downstream NLP analysis. Using the SUBA corpus, the neural network classifier predicted interactions between protein name, subcellular localisation and experimental methodology with an average precision, recall rate, accuracy and F1 scores of 95.1%, 82.8%, 89.3% and 88.4% respectively (n = 30). Comparable scoring metrics were obtained using the CropPAL database as an independent testing dataset that stores protein subcellular localisation in crop species, demonstrating wide applicability of prediction model. We provide a framework for extracting protein functional features from unstructured text in the literature with high accuracy, improving data dissemination and unlocking the potential of big data text analytics for generating new hypotheses.Rakesh David, Rhys‑Joshua D. Menezes, Jan De Klerk, Ian R. Castleden, Cornelia M. Hooper, Gustavo Carneiro and Matthew Gilliha

Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study

OBJECTIVE: Several lines of evidence suggest that estrogens influence the development of osteoarthritis (OA). The aim of this study was to explore the association of two common polymorphisms within the aromatase (CYP19A1) and estrogen receptor (ER) alpha (ESR1) genes with severe OA of the lower limbs. METHODS: The rs1062033 (CYP19A1) and rs2234693 (ESR1) single nucleotide polymorphisms were genotyped in 5528 individuals (3147 patients with severe hip or knee OA, and 2381 controls) from four centres in Spain and the United Kingdom. Gene expression was measured in femoral bone samples from a group of patients. RESULTS: In the global analysis, both polymorphisms were associated with OA, but there was a significant sex interaction. The GG genotype at rs1062033 was associated with an increased risk of knee OA in women [odds ratio (OR) 1.23; P=0.04]. The CC genotype at rs2234693 tended to be associated with reduced OA risk in women (OR 0.76, P=0.028, for knee OA; OR=0.84, P=0.076 for hip OA), but with increased risk of hip OA in men (OR 1.28; P=0.029). Women with unfavourable genotypes at both loci had an OR of 1.61 for knee OA (P=0.006). The rs1062033 genotype associated with higher OA risk was also associated with reduced expression of the aromatase gene in bone. CONCLUSIONS: Common genetic variations of the aromatase and ER genes are associated with the risk of severe OA of the large joints of the lower limb in a sex-specific manner. These results are consistent with the hypothesis that estrogen activity may influence the development of large-joint OA

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact

Improving the false-negative rate of CT in acute appendicitis-Reassessment of CT images by body imaging radiologists: A blinded prospective study

Purpose: To compare the accuracy of computed tomography (CT) analyzed by individual radiology staff members and body imaging radiologists in a non-academic teaching hospital for the diagnosis of acute appendicitis. Patients and methods: In a prospective study 199 patients with suspected acute appendicitis were examined with unenhanced CT. CT images were pre-operatively analyzed by one of the 12 members of the radiology staff. In a later stage two body imaging radiologist reassessed all CT images without knowledge of the surgical findings and without knowledge of the primary CT diagnosis. The results, independently reported, were correlated with surgical and histopathologic findings. Results: In 132 patients (66%) acute appendicitis was found at surgery, in 67 patients (34%) a normal appendix was found. The sensitivity of the primary CT analysis and of the reassessment was 76% and 88%, respectively; the specificity was 84% and 87%; the positive predictive value was 90% and 93%; the negative predictive value was 64% and 78%; and the accuracy was 78% and 87%. Conclusion: Reassessment of CT images for acute appendicitis by body imaging radiologists results in a significant improvement of sensitivity, negative predictive value and accuracy. To prevent false-negative interpretation of CT images in acute appendicitis the expertise of the attending radiologist should be considered. (C) 2008 Elsevier Ireland Ltd. All rights reserved.Vascular Surger

Psychological well-being and sexarche in women with polycystic ovary syndrome

Background The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well-being as well as sexarche. Methods Patients (n = 1148) underwent standardized clinical evaluation. Psychological well-being was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed. Result SAmenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively). Conclusions Our Results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics

MicroRNA signatures in malignant pleural mesothelioma effusions

Malignant pleural mesothelioma (MPM) is an incurable cancer of the pleura that can be difficult to diagnose. Biomarkers for an easier and/or earlier diagnosis are needed. Approximately 90% of MPM patients develop a pleural effusion (PE). PEs are ideal sources of biomarkers as the fluid would almost always require drainage for diagnostic and/or therapeutic reasons. However, differentiating MPM PE from PE caused by other diseases can be challenging. MicroRNAs are popular biomarkers given their stable expression in tissue and fluid. MicroRNAs have been analysed in PE cytology samples for the diagnosis of MPM but have not been measured in frozen/fresh PE. We hypothesise that microRNAs expressed in PE are biomarkers for MPM. TaqMan OpenArray was used to analyse over 700 microRNAs in PE cells and supernatants from 26 MPMs and 21 other PE-causing diseases. In PE cells, combining miR-143, miR-210, and miR-200c could differentiate MPM with an area under the curve (AUC) of 0.92. The three-microRNA signature could also discriminate MPM from a further 40 adenocarcinomas with an AUC of 0.9887. These results suggest that the expression of miR-143, miR-210, and miR-200c in PE cells might provide a signature for diagnosing MPM

ESHRE guideline: routine psychosocial care in infertility and medically assisted reproduction-a guide for fertility staffdagger

Item does not contain fulltextSTUDY QUESTION: Based on the best available evidence in the literature, what is the optimal management of routine psychosocial care at infertility and medically assisted reproduction (MAR) clinics? SUMMARY ANSWER: Using the structured methodology of the Manual for the European Society of Human Reproduction and Embryology (ESHRE) Guideline Development, 120 recommendations were formulated that answered the 12 key questions on optimal management of routine psychosocial care by all fertility staff. WHAT IS ALREADY KNOWN: The 2002 ESHRE Guidelines for counselling in infertility has been a reference point for best psychosocial care in infertility for years, but this guideline needed updating and did not focus on routine psychosocial care that can be delivered by all fertility staff. STUDY, DESIGN, SIZE, DURATION: This guideline was produced by a group of experts in the field according to the 12-step process described in the ESHRE Manual for Guideline Development. After scoping the guideline and listing a set of 12 key questions in PICO (Patient, Intervention, Comparison and Outcome) format, thorough systematic searches of the literature were conducted; evidence from papers published until April 2014 was collected, evaluated for quality and analysed. A summary of evidence was written in a reply to each of the key questions and used as the basis for recommendations, which were defined by consensus within the guideline development group (GDG). Patient and additional clinical input was collected during the scoping and the review phase of the guideline development. PARTICIPANTS/MATERIALS, SETTING, METHODS: The guideline group, comprising psychologists, two medical doctors, a midwife, a patient representative and a methodological expert, met three times to discuss evidence and reach consensus on the recommendations. MAIN RESULTS AND THE ROLE OF CHANCE THE GUIDELINE PROVIDES: 120 recommendations that aim at guiding fertility clinic staff in providing optimal evidence-based routine psychosocial care to patients dealing with infertility and MAR. The guideline is written in two sections. The first section describes patients' preferences regarding the psychosocial care they would like to receive at clinics and how this care is associated with their well-being. The second section of the guideline provides information about the psychosocial needs patients experience across their treatment pathway (before, during and after treatment) and how fertility clinic staff can detect and address these. Needs refer to conditions assumed necessary for patients to have a healthy experience of the fertility treatment. Needs can be behavioural (lifestyle, exercise, nutrition and compliance), relational (relationship with partner if there is one, family friends and larger network, and work), emotional (well-being, e.g. anxiety, depression and quality of life) and cognitive (treatment concerns and knowledge). LIMITATIONS, REASONS FOR CAUTION: We identified many areas in care for which robust evidence was lacking. Gaps in evidence were addressed by formulating good practice points, based on the expert opinion of the GDG, but it is critical for such recommendations to be empirically validated. WIDER IMPLICATIONS OF THE FINDINGS: The evidence presented in this guideline shows that providing routine psychosocial care is associated with or has potential to reduce stress and concerns about medical procedures and improve lifestyle outcomes, fertility-related knowledge, patient well-being and compliance with treatment. As only 45 (36.0%) of the 125 recommendations were based on high-quality evidence, the guideline group formulated recommendations to guide future research with the aim of increasing the body of evidence. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with literature searches, and with the implementation of the guideline. The GDG members did not receive payment. S.G., E.D., C.d.K., M.E., U.V.d.B., C.L.-J. and N.V. report no conflicts of interest. J.B. reports grants from Merck & Co, consulting fees from Merck Serono S.A. and Speaker's fees from Merck Serono S.A. P.T. reports consulting fees from the German government and being the Chair of the German Society for Fertility Counselling. C.V. reports consulting fees from Merck Serono S.A. C.M.V. reports being adviser in projects for Merck Serono S.A. and Ferring S.A. on patient educational material. T.W. reports speaker's fees from Repromed, DGPM, Breitbach, DAAG, fiore, LPTW, MSD, salary/position funding at TAB-beim-Bundestag, BZgA, and being the Vice-chair of the German Society for Fertility Counselling. TRIAL REGISTRATION NUMBER: NA