Use of Word Embeddings in a Literature-Based Discovery System

Since Don R. Swanson’s first works in the field of Literature-Based Discovery (LBD) in the 1980s, there has been a keen interest in the process’s abilities to retrieve new relationships from already published articles. In addition to this, the explosion of biomedical literature added to the public domain daily makes these automated systems more vital as time goes on with a researchers ability to keep up to date with their specialism let alone any potentially related fields. Furthermore, this emergence of LBD and the explosion of published knowledge has come at a time where the pharmaceutical industry is beginning to understand the importance of repurposing existing compounds as a method of reducing costs whilst still managing new and old conditions. This thesis proposes a system that utilises the Word2Vec group of models to implement an LBD system. These tasks are undertaken utilising seven different corpora comprised of biomedical articles related to varying levels from Raynaud Disease to Hematological journals published on the MEDLINE database and retrieved through PUBMED. This data was then fed through a specially developed pre-processing pipeline to normalise the data and then passed through a Word2Vec model and using the cosine similarity metric the most semantically similar phrases to any phrases containing the word "Raynaud". Finally, these phrases are filtered based upon their UMLS semantic type and compared to the terms found by both Weeber and Swanson to evaluate the usefulness of this method. These experiments found that when using these corpora the majority of links, an average of 88% of B-Terms for Open Discovery and an average of 81% for Closed Discovery, can still be formed. However there is still a large degree of manual curation necessary due to the imprecision of the process. This thesis shows that the development and implementation of such a system with improvements to its precision can be of use to the research community

Antibacterial properties of novel Eumelanin-Inspired Phenylene Indolyne derivatives

BACKGROUND: The eumelanin core represents a novel compound having the intrinsic ability to act as scaffolding for functional groups which may possess antibacterial properties. The purpose of this study was to investigate the antibacterial potential of eumelanin-inspired phenylene indolyne (EIPE) derivatives EIPE-1 and EIPE-HCl which are hydrophobic and hydrophilic, respectively.METHODS: A standardized disk agar diffusion bioassay was employed to determine the susceptibility and resistance levels of 12 gram-positive and 13 gram-negative bacteria to nonpolar and polar EIPE derivatives. The bioassay was performed by dissolving the compounds in dimethyl sulfoxide and impregnating filter paper disks which were placed onto Mueller Hinton agar plates spread inoculated in a standardized manner to obtain even cell lawns after incubation for 18±1 hours at 37°C. Zones of growth inhibition were measured with the aid of electronic calipers.RESULTS: Five strains of Staphylococcus aureus, plus Bacillus subtilis and Staphylococcus epidermidis were all found to be susceptible to the hydrophobic derivative EIPE-1, while other gram-positive and all gram-negative organisms exhibited resistant phenotypes at potencies tested. The more polar EIPE-HCl derivative failed to inhibit growth of any of the organisms examined, regardless of gram reactivity.CONCLUSION: Hydrophobic EIPE derivative EIPE-1 clearly possesses a gram-positive antibacterial spectrum, although only certain organisms are susceptible at the potencies employed for this study. The susceptibility of two methicillin-resistant S. aureus strains (SFL 8 and SFL 64) to EIPE-1 suggests that its mechanism of action does not involve the penicillin-binding proteins of peptidoglycan biosynthesis targeted by mainstream B-lactam antibiotics. The uniform resistance of 13 phylogenetically disparate gram-negative bacteria supports the notion that intrinsic outer membrane exclusion properties may play a role in the mechanism underlying their phenotypic resistance to the molecule. The more polar EIPE-HCl possesses no antibacterial properties at the potencies examined here. Future work will include performing minimal inhibitory concentration bioassays to quantitatively describe susceptibly in selected gram-positive bacteria. In addition, batch culture growth kinetics assays will be crucial to learning the cellular and molecular mechanisms responsible for susceptibility and resistance to EIPE-1

Demonstration of a Literature Based Discovery System based on Ontologies, Semantic Filters and Word Embeddings for the Raynaud Disease-Fish Oil Rediscovery

A novel literature-based discovery system based on UMLS Ontologies, Semantic Filters, Statistics, and Word Embeddings was developed and validated against the well-established Raynaud’s disease – Fish Oil discovery by mining different size and specificity corpora of Pubmed titles and abstracts. Results show an ‘inverse effect’ between open versus closed discovery search modes. In open discovery, a more general and bigger corpus (Vascular disease or Perivascular disease) produces better results than a more specific and smaller in size corpus (Raynaud disease), whereas in closed discovery, the exact opposite is true

How institutional forces, ideas and actors shaped population health planning in Australian regional primary health care organisations

BACKGROUND: Worldwide, there are competing norms driving health system changes and reorganisation. One such norm is that of health systems’ responsibilities for population health as distinct from a focus on clinical services. In this paper we report on a case study of population health planning in Australian primary health care (PHC) organisations (Medicare Locals, 2011–2015). Drawing on institutional theory, we describe how institutional forces, ideas and actors shaped such planning. METHODS: We reviewed the planning documents of the 61 Medicare Locals and rated population health activities in each Medicare Local. We also conducted an online survey and 50 interviews with Medicare Local senior staff, and an interview and focus group with Federal Department of Health staff. RESULTS: Despite policy emphasis on population health, Medicare Locals reported higher levels of effort and capacity in providing clinical services. Health promotion and social determinants of health activities were undertaken on an ad hoc basis. Regulatory conditions imposed by the federal government including funding priorities and time schedules, were the predominant forces constraining population health planning. In some Medicare Locals, this was in conflict with the normative values and what Medicare Locals felt ought to be done. The alignment between the governmental and the cultural-cognitive forces of a narrow biomedical approach privileged clinical practice and ascribed less legitimacy to action on social determinants of health. Our study also shed light on the range of PHC actors and how their agency influenced Medicare Locals’ performance in population health. The presence of senior staff or community boards with a strong commitment to population health were important in directing action towards population health and equity. CONCLUSIONS: There are numerous institutional, normative and cultural factors influencing population health planning. The experience of Australian Medicare Locals highlights the difficulties of planning in such a way that the impact of the social determinants on health and health equity are taken into account. The policy environment favours a focus on clinical services to the detriment of health promotion informed by a social determinants focus

ImaYDiT - Imagining young disabled people's transitions in a time of major societal change: Research project report

ImaYDiT was funded by DRILL – Disability Research for Independent Living and Learning. This is supported by the Big Lottery Fund. WiltsCIL staff, members of WiltsCIL CoproductionGroup and researchers at UWE came up with the original idea for this project. We wanted to support young disabled people to explore and re-imagine their adult lives and have the best future. This involved taking an ‘assets-based’ approach. This is where we focus on what people can do- rather than what they can’t do – which is a ‘deficit approach’. We also thought that there is not enough research about the whole of young disabled people’s lives. Instead a lot of research only concentrates on transitions through the benefits and service system.Wiltshire Social Services and the Wiltshire Parent Council helped steer the project because, where we could, we also wanted to put young disabled people’s hopes and dreams into action.We want to understand how this group of young disabled people can be supported to become the next generation who are aware of their rights, with ambitions for their futures and able to establish meaningful and independent adult lives

Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?

Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by 'buzzing' (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance, allowing genes for disease susceptibility to persist in plant populations. We speculate that enhanced pollinator service for infected individuals in wild plant populations might provide mutual benefits to the virus and its susceptible hosts.Major funding for this project was provided to JPC by the Leverhulme Trust (Grant numbers RPG-2012-667 and F/09741/F: https://www. leverhulme.ac.uk/). Additional funding to JPC and studentships to support JHW and SCG came from the Biotechnological and Biological Sciences Research Council (Grant number BB/J011762/1: http://www.bbsrc.ac.uk/). Other additional funding was obtained from the Isaac Newton Trust (http://www. newtontrust.cam.ac.uk/: grant number 12.07/I to AMM).This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/:10.1371/journal.ppat.100579

Novel mechanistic view of catalytic ozonation of gaseous toluene by dual-site kinetic modelling

The catalytic ozonation of VOCs is a promising approach for degradation of indoor VOCs, such as gaseous toluene. However, the mechanism and relevant kinetic steps involved in this reaction remain unclear. In this study, the catalytic ozonation of toluene over MnO2/graphene was investigated using the empirical power law model and classic Langmuir-Hinshelwood single-site (denoted as L-Hs) mechanism. The apparent activation energy determined using the power law model was 29.3±2.5 kJ mol−1. This finding indicated that the catalytic ozonation of toluene over MnO2/graphene was a heterogeneous reaction, and the Langmuir-Hinshelwood mechanism was applicable. However, the L-Hs mechanism did not fit the experimental data, suggesting that the reaction was non-single-site governed. A novel Langmuir-Hinshelwood dual-site (denoted as L-Hd) mechanism was then proposed to explain the experimental observations of the catalytic ozonation of toluene over MnO2/graphene through a steady-state kinetic study. This mechanism was based on the hypothesis that MnO2 was responsible for ozone decomposition and toluene adsorption on graphene; these two types of adsorption were coupled by an adjacent attack. Furthermore, XPS results confirmed the presence of a strong connection between MnO2 and graphene sites on the surface of MnO2/graphene. This connection allowed the adjacent attack and validated the dual-site mechanism. The L-Hd model was consistent with the predicted reaction rate of toluene removal with a correlation coefficient near unity (r2 = 0.9165). Moreover, the physical criterion was in accordance with both enthalpy and entropy of toluene adsorption constraints. Fulfillment of mathematical and physical criteria indicated the catalytic ozonation of toluene over MnO2/graphene can be well described by the L-Hd mechanism. This study helps understand the catalytic ozonation of toluene over MnO2/graphene in a closely mechanistic view

Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570