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https://www.readbyqxmd.com/read/28423765/evaluation-of-machine-learning-methods-to-predict-coronary-artery-disease-using-metabolomic-data
#1
Henrietta Forssen, Riyaz Patel, Natalie Fitzpatrick, Aroon Hingorani, Adam Timmis, Harry Hemingway, Spiros Denaxas
Metabolomic data can potentially enable accurate, non-invasive and low-cost prediction of coronary artery disease. Regression-based analytical approaches however might fail to fully account for interactions between metabolites, rely on a priori selected input features and thus might suffer from poorer accuracy. Supervised machine learning methods can potentially be used in order to fully exploit the dimensionality and richness of the data. In this paper, we systematically implement and evaluate a set of supervised learning methods (L1 regression, random forest classifier) and compare them to traditional regression-based approaches for disease prediction using metabolomic data...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28409546/clinical-correlation-with-failure-of-endovenous-therapy-for-leg-swelling
#2
Ahmad Alsheekh, Anil Hingorani, Natalie Marks, Yuriy Ostrozhynskyy, Enrico Ascher
Background The development and use of minimally invasive procedures provide improved options for the management of symptoms of chronic venous insufficiency. While many patients with iliac venous occlusive disease and superficial venous insufficiency improve with combined iliac venous stenting and correction of superficial venous reflux, some patients have symptoms which persist. The goal of this study was to identify clinical factors related to persistent symptoms in patients with leg swelling after treatment of both iliac vein stenting and thermal ablation...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28399267/development-of-a-%C3%AE-9-tetrahydrocannabinol-amino-acid-dicarboxylate-prodrug-with-improved-ocular-bioavailability
#3
Goutham R Adelli, Prakash Bhagav, Pranjal Taskar, Tushar Hingorani, Sara Pettaway, Waseem Gul, Mahmoud A ElSohly, Michael A Repka, Soumyajit Majumdar
Purpose: The aim of the present study was to evaluate the utility of the relatively hydrophilic Δ9-tetrahydrocannabinol (THC) prodrugs, mono and di-valine esters (THC-Val and THC-Val-Val) and the amino acid (valine)-dicarboxylic acid (hemisuccinate) ester (THC-Val-HS), with respect to ocular penetration and intraocular pressure (IOP) lowering activity. THC, timolol, and pilocarpine eye drops were used as controls. Methods: THC-Val, THC-Val-Val, and THC-Val-HS were synthesized and chemically characterized...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28356508/the-druggable-genome-and-support-for-target-identification-and-validation-in-drug-development
#4
Chris Finan, Anna Gaulton, Felix A Kruger, R Thomas Lumbers, Tina Shah, Jorgen Engmann, Luana Galver, Ryan Kelley, Anneli Karlsson, Rita Santos, John P Overington, Aroon D Hingorani, Juan P Casas
Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications...
March 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28349888/screening-for-familial-hypercholesterolaemia-in-childhood-avon-longitudinal-study-of-parents-and-children-alspac
#5
Marta Futema, Jackie A Cooper, Marietta Charakida, Christopher Boustred, Naveed Sattar, John Deanfield, Debbie A Lawlor, Nicholas J Timpson, Steve E Humphries, Aroon D Hingorani
BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal-dominant disease with frequency of 1/500 to 1/250 that leads to premature coronary heart disease. New approaches to identify FH mutation-carriers early are needed to prevent premature cardiac deaths. In a cross-sectional study of the Avon Longitudinal Study of Parents and Children (ALSPAC), we evaluated the biochemical thresholds for FH screening in childhood, and modelled a two-stage biochemical and sequencing screening strategy for FH detection...
March 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28330434/is-there-an-effect-of-race-ethnicity-on-early-complications-of-iliac-vein-stenting
#6
Ahmad Alsheekh, Anil Hingorani, Samson Ferm, Pavel Kibric, Afsha Aurshina, Natalie Marks, Enrico Ascher
Background There have been well-documented implications of race/ethnicity on the outcome of various vascular diseases. Little literature has examined the effect of race/ethnicity on venous disease. Iliac vein stenting is an emerging technology in treating chronic venous insufficiency. To further characterize this disease and its treatment, we chose to study the effect of selected clinical factors including race/ethnicity on the early complications of non-thrombotic iliac vein stenting. Methods In this observational study, data analysis was performed for 623 patients with chronic venous insufficiency who underwent iliac vein stenting during the time period from August 2012 to September 2014...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28299667/runx3-and-cell-fate-decisions-in-pancreas-cancer
#7
Martin C Whittle, Sunil R Hingorani
The RUNX family transcription factors are critical regulators of development and frequently dysregulated in cancer. RUNX3, the least well characterized of the three family members, has been variously described as a tumor promoter or suppressor, sometimes with conflicting results and opinions in the same cancer and likely reflecting a complex role in oncogenesis. We recently identified RUNX3 expression as a crucial determinant of the predilection for pancreatic ductal adenocarcinoma (PDA) cells to proliferate locally or promulgate throughout the body...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28279251/oral-anticoagulants-for-primary-prevention-treatment-and-secondary-prevention-of-venous-thromboembolic-disease-and-for-prevention-of-stroke-in-atrial-fibrillation-systematic-review-network-meta-analysis-and-cost-effectiveness-analysis
#8
Jonathan Ac Sterne, Pritesh N Bodalia, Peter A Bryden, Philippa A Davies, Jose A López-López, George N Okoli, Howard Hz Thom, Deborah M Caldwell, Sofia Dias, Diane Eaton, Julian Pt Higgins, Will Hollingworth, Chris Salisbury, Jelena Savović, Reecha Sofat, Annya Stephens-Boal, Nicky J Welton, Aroon D Hingorani
BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs...
March 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28254179/neutrophil-counts-and-initial-presentation-of-12-cardiovascular-diseases-a-caliber-cohort%C3%A2-study
#9
Anoop Dinesh Shah, Spiros Denaxas, Owen Nicholas, Aroon D Hingorani, Harry Hemingway
BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England...
March 7, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28225386/acute-myocardial-infarction-and-antiphospholipid-antibody-syndrome-a-systematic-review
#10
Salik Nazir, Niranjan Tachamo, Saroj Lohani, Rittu Hingorani, Dilli R Poudel, Anthony Donato
BACKGROUND: Antiphospholipid antibody syndrome (APS) is a disorder associated with both arterial and venous thromboembolic disease, including acute myocardial infarction (AMI). Given that management with anticoagulants is critical and differs from usual AMI care, identification of key discriminators of patients with AMI with APS is important. METHODS: We performed an English-language systematic review of the literature of cases and case series of patients with AMI and APS from inception until 20 March 2016, collecting demographics, investigations, and outcomes...
February 20, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28218913/ligand-promoted-protein-folding-by-biased-kinetic-partitioning
#11
Karan S Hingorani, Matthew C Metcalf, Derrick T Deming, Scott C Garman, Evan T Powers, Lila M Gierasch
Protein folding in cells occurs in the presence of high concentrations of endogenous binding partners, and exogenous binding partners have been exploited as pharmacological chaperones. A combined mathematical modeling and experimental approach shows that a ligand improves the folding of a destabilized protein by biasing the kinetic partitioning between folding and alternative fates (aggregation or degradation). Computationally predicted inhibition of test protein aggregation and degradation as a function of ligand concentration are validated by experiments in two disparate cellular systems...
April 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28170093/topical-treatments-for-blepharokeratoconjunctivitis-in-children
#12
REVIEW
Michael O'Gallagher, Catey Bunce, Melanie Hingorani, Frank Larkin, Stephen Tuft, Annegret Dahlmann-Noor
BACKGROUND: Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation...
February 7, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28135092/evolutionary-covariance-combined-with-molecular-dynamics-predicts-a-framework-for-allostery-in-the-muts-dna-mismatch-repair-protein
#13
Bharat Lakhani, Kelly M Thayer, Manju M Hingorani, David L Beveridge
Mismatch repair (MMR) is an essential, evolutionarily conserved pathway that maintains genome stability by correcting base-pairing errors in DNA. Here we examine the sequence and structure of MutS MMR protein to decipher the amino acid framework underlying its two key activities-recognizing mismatches in DNA and using ATP to initiate repair. Statistical coupling analysis (SCA) identified a network (sector) of coevolved amino acids in the MutS protein family. The potential functional significance of this SCA sector was assessed by performing molecular dynamics (MD) simulations for alanine mutants of the top 5% of 160 residues in the distribution, and control nonsector residues...
March 9, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28007107/patient-reported-outcome-measuring-tools-in-cataract-surgery-clinical-comparison-at%C3%A2-a-tertiary-hospital
#14
Simon S M Fung, Joshua Luis, Badrul Hussain, Catey Bunce, Melanie Hingorani, Joanne Hancox
PURPOSE: To assess the performance of patient-reported outcome measure questionnaires and determine their appropriateness for routine use in cataract patients. SETTING: Moorfields Eye Hospital, London, United Kingdom. DESIGN: Prospective cohort study. METHODS: Patients having cataract surgery between February and March 2013 were recruited. The following 4 questionnaires-Catquest-9SF, EuroQol 5-dimensions questionnaire (EQ-5D) and visual analog scale (EQ-VAS), National Eye Institute Socioemotional Scale (NEI-SES), and short-form Visual Function Index (VF-8R)-were completed preoperatively and 3 weeks and 3 months postoperatively...
December 2016: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/27987614/the-bull-s-eye-sign-and-other-suprainguinal-venographic-findings-to-limit-the-use-of-intravascular-ultrasound-in-patients-with-severe-venous-stasis
#15
Enrico Ascher, Justin Eisenberg, Natalie Bauer, Natalie Marks, Anil Hingorani, Syed Rizvi
OBJECTIVE: When assessing the common femoral and suprainguinal veins in patients with venous stasis, it is generally agreed that use of intravascular ultrasound (IVUS) is mandatory. This widely held dogma is reinforced by the fact that extrinsic compression of the iliac veins does not reproduce images consistent with eccentric stenosis as one sees in the arterial system. In an attempt to identify a subgroup of patients where the use of IVUS could be averted, we analyzed and carefully evaluated the images of patients who had both standard contrast venograms and IVUS examinations...
January 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/27977033/medical-management-of-blepharokeratoconjunctivitis-in-children-a-delphi-consensus
#16
Moritz Claudius Daniel, Michael O'Gallagher, Melanie Hingorani, Daniel F Larkin, Stephen Tuft, Annegret Dahlmann-Noor
PURPOSE: To describe a pragmatic approach to the medical management of blepharokeratoconjunctivitis in children, based on published evidence and clinical experience. METHODS: The authors used the Delphi consensus method to explore the preferred management patterns of four senior clinicians at one institution to reach agreement on indications and dosage schedules for commonly used treatments. Four iterations were created, with electronic questionnaires distributed via an online survey platform...
December 8, 2016: Journal of Pediatric Ophthalmology and Strabismus
https://www.readbyqxmd.com/read/27972374/cost-effectiveness-analysis-of-screening-strategies-for-atrial-fibrillation-in-england-and-wales
#17
H Thom, W Hollingworth, A McAleenan, P Davies, J Higgins, G N Okoli, J Sterne, G Feder, D Eaton, A Hingorani, C Fawsitt, T Lobban, P A Bryden, A Richards, R Sofat, N J Welton
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27972260/systematic-review-and-meta-analysis-of-accuracy-of-diagnostic-tests-for-screen-detection-of-atrial-fibrillation
#18
H Thom, A McAleenan, P Davies, G N Okoli, J Higgins, W Hollingworth, J Sterne, G Feder, D Eaton, A Hingorani, C Fawsitt, T Lobban, P A Bryden, A Richards, R Sofat, N J Welton
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27934157/photopolymerization-of-diacetylene-on-aligned-multiwall-carbon-nanotube-microfibers-for-high-performance-energy-devices
#19
Mani Ulaganathan, Reinack Varghese Hansen, Nateisha Drayton, Hardik Hingorani, R Govindan Kutty, Hrishikesh Joshi, Sivaramapanicker Sreejith, Zheng Liu, Jinglei Yang, Yanli Zhao
Linear two-dimensional materials have recently attracted an intense interest for supercapacitors because of their potential uses as electrodes in next-generation wearable electronics. However, enhancing the electrochemical properties of these materials without complicated structural modifications remains a challenge. Herein, we present the preparation of a hybrid electrode system via polydiacetylene (PDA) cloaking on the surface of aligned multiwall carbon nanotubes (MWCNTs) through self-assembly based in situ photopolymerization...
December 7, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27913808/treatment-of-upper-extremity-venous-aneurysms-with-a-polytetrafluoroethylene-covered-stent
#20
David Parizh, Jesse Victory, Syed Ali Rizvi, Anil Hingorani, Enrico Ascher
Background Venous aneurysms of the upper torso are uncommon in contrast to the abdomen and lower extremities. Mostly silent, they can cause significant morbidity. Large or symptomatic venous aneurysms are generally treated with open resection. To our knowledge, there are no documented cases of head and neck venous aneurysms treated by a hybrid endovascular and open approach. Case Presentation A 56-year-old female presented with the complaint of pain and increasing size of a supraclavicular mass. Imaging revealed a large saccular aneurysm of the subclavian vein with the presence of a large intramural thrombus on computed tomography scan with contrast...
January 1, 2016: Vascular
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