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| 1 | Neoadjuvant radiotherapy for rectal cancer management显示文摘Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer. | Gerard Feeney Rishabh Sehgal Margaret Sheehan Aisling Hogan Mark Regan Myles Joyce Michael Kerin | 2019 | World Journal of Gastroenterology2019,25,33: | 28 |
| 2 | Challenges in the management of pancreatic exocrine insufficiency显示文摘Pancreatic exocrine insufficiency(PEI) occurs when the insufficient secretion or function of pancreatic enzymes leads to maldigestion, most commonly as a result of chronic pancreatitis and pancreatic cancer. The condition is associated with significant morbidity and reductions in quality of life, even in milder forms. The challenges in approaching this condition include the non-specific presentation of mild to moderate PEI, and the lack of a convenient, accurate diagnostic test in this cohort. Classical symptoms appear late in the disease, and the diagnosis should be considered before steatorrhoea develops. Direct pancreatic function tests are the reference standard for diagnosis, but are invasive and not widely available. The faecal elastase-1(FE-1) stool test is widely available and has been shown to be as effective as the 13 C-mixed triglyceride breath test in more advanced disease. We recommend a pragmatic diagnostic approach that combines clinical history, assessment of nutritional status and measurement of FE-1. The critical first step is to consider the diagnosis. Once the diagnosis is confirmed, pancreatic enzyme replacement therapy should be initiated. The variety of enzyme preparations and recommended dosing regimens can present a challenge when selecting an adequate initial dose. Non-response should be actively sought and addressed in a systematic manner. This article discusses these challenges, and presents a practical approach to the diagnosis and management of PEI. | Benjamin Myles Shandro Rani Nagarajah Andrew Poullis | 2018 | World Journal of Gastrointestinal Pharmacology and Therapeutics2018,9,5: | 5 |
| 3 | 针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。 | Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) | 2020 | 英国医学杂志中文版2020,23,9: | 5 |
| 4 | Transcranial direct current stimulation for auditory verbal hallucinations:a systematic review of clinical trials显示文摘Transcranial direct current stimulation(tDCS)has been reportedly beneficial for different neurodegenerative disorders.tDCS has been reported as a potential adjunctive or alternative treatment for auditory verbal hallucination(AVH).This study aims to review the effects of tDCS on AVH in patients with schizophrenia through combining the evidence from randomized clinical trials(RCTs).The databases of PsycINFO(2000–2019),PubMed(2000–2019),EMBASE(2000–2019),CINAHL(2000–2019),Web of Science(2000–2019),and Scopus(2000–2019)were systematically searched.The clinical trials with RCT design were selected for final analysis.A total of nine RCTs were eligible and included in the review.Nine RCTs were included in the final analysis.Among them,six RCTs reported a significant reduction of AVH after repeated sessions of tDCS,whereas three RCTs did not show any advantage of active tDCS over sham tDCS.The current studies showed an overall decrease of approximately 28%of AVH after active tDCS and 10%after sham tDCS.The tDCS protocols targeting the sensorimotor frontal-parietal network showed greater treatment effects compared with the protocols targeting other regions.In this regard,cathodal tDCS over the left temporoparietal area showed inhibitory effects on AVHs.The most effective tDCS protocol on AVHs was twice-daily sessions(2 mA,20-minute duration)over 5 consecutive days(10 sessions)with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporal area.Some patient-specific and diseasespecific factors such as young age,nonsmoking status,and higher frequencies of AVHs seemed to be the predictors of treatment response.Taken together,the results of tDCS as an alternative treatment option for AVH show controversy among current literatures,since not all studies were positive.However,the studies targeting the same site of the brain showed that the tDCS could be a promising treatment option to reduce AVH.Further RCTs,with larger sample sizes,should be conducted to reach a conclusion on the efficacy of tDCS for AVH and to develop an effective therapeutic protocol for clinical setting. | Samaneh Rashidi Myles Jones Eric Murillo-Rodriguez Sergio Machado Youguo Hao Ali Yadollahpour | 2021 | Neural Regeneration Research2021,16,4: | 4 |
| 5 | DMP1 prevents osteocyte alterations,FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease显示文摘During chronic kidney disease (CKD),alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular mortality.The osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization,but its effects in CKD are unknown.We tested the hypothesis that DMP1 supplementation in CKD would improve bone health,prevent FGF23 elevations and minimize consequent adverse cardiovascular outcomes.We investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3^-/- mouse model of CKD.Col4a3^-/- mice demonstrated impaired kidney function,reduced bone DMP1 expression,reduced bone mass,altered osteocyte morphology and connectivity,increased osteocyte apoptosis,increased serum FGF23,hyperphosphatemia,left ventricular hypertrophy (LVH),and reduced survival.Genetic or pharmacological supplementation of DMP1 in Col4a3^-/- mice prevented osteocyte apoptosis,preserved osteocyte networks,corrected bone mass,partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription,and further increased serum phosphate.Despite impaired kidney function and worsened hyperphosphatemia,DMP1 prevented development of LVH and improved Col4a3^-/- survival.Our data suggest that CKD reduces DMP1 expression,whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD. | Corey Dussold Claire Gerber Samantha White Xueyan Wang Lixin Qi Connor Francis Maralee Capella Guillaume Courbon Jingya Wang Chaoyuan Li Jian Q. Feng Tamara Isakova Myles Wolf Valentin David Aline Martin | 2019 | Bone Research2019,7,2: | 4 |
| 6 | Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease显示文摘Bone-produced fibroblast growth factor 23(FGF23)increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease(CKD).Neutrophil gelatinase-associated lipocalin(NGAL or lipocalin 2;LCN2 the murine homolog)is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression.We investigated bone FGF23 regulation by circulating LCN2.At 23 weeks,Col4a3KO mice showed impaired kidney function,increased levels of kidney and serum LCN2,increased bone and serum FGF23,anemia,and left ventricular hypertrophy(LVH).Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23.Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation,but not iron deficiency or phosphate,and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells.These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD.LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD. | Guillaume Courbon Connor Francis Claire Gerber Samantha Neuburg Xueyan Wang Emily Lynch Tamara Isakova Jodie LBabitt Myles Wolf Aline Martin Valentin David | 2021 | Bone Research2021,9,3: | 4 |
| 7 | Genome-wide association studies in apple reveal loci of large effect controlling apple polyphenols显示文摘Apples are a nutritious food source with significant amounts of polyphenols that contribute to human health and wellbeing,primarily as dietary antioxidants.Although numerous pre-and post-harvest factors can affect the composition of polyphenols in apples,genetics is presumed to play a major role because polyphenol concentration varies dramatically among apple cultivars.Here we investigated the genetic architecture of apple polyphenols by combining high performance liquid chromatography(HPLC)data with~100,000 single nucleotide polymorphisms(SNPs)from two diverse apple populations.We found that polyphenols can vary in concentration by up to two orders of magnitude across cultivars,and that this dramatic variation was often predictable using genetic markers and frequently controlled by a small number of large effect genetic loci.Using GWAS,we identified candidate genes for the production of quercitrin,epicatechin,catechin,chlorogenic acid,4-O-caffeoylquinic acid and procyanidins B1,B2,and C1.Our observation that a relatively simple genetic architecture underlies the dramatic variation of key polyphenols in apples suggests that breeders may be able to improve the nutritional value of apples through markerassisted breeding or gene editing. | Kendra AMcClure YuiHui Gong Jun Song Melinda Vinqvist-Tymchuk Leslie Campbell Palmer Lihua Fan Karen Burgher-MacLellan ZhaoQi Zhang Jean-Marc Celton Charles FForney ZoëMigicovsky Sean Myles | 2019 | Horticulture Research2019,6,1: | 3 |
| 8 | Apple whole genome sequences:recent advances and new prospects显示文摘In 2010,a major scientific milestone was achieved for tree fruit crops:publication of the first draft whole genome sequence(WGS)for apple(Malus domestica).This WGS,v1.0,was valuable as the initial reference for sequence information,fine mapping,gene discovery,variant discovery,and tool development.A new,high quality apple WGS,GDDH13 v1.1,was released in 2017 and now serves as the reference genome for apple.Over the past decade,these apple WGSs have had an enormous impact on our understanding of apple biological functioning,trait physiology and inheritance,leading to practical applications for improving this highly valued crop.Causal gene identities for phenotypes of fundamental and practical interest can today be discovered much more rapidly.Genome-wide polymorphisms at high genetic resolution are screened efficiently over hundreds to thousands of individuals with new insights into genetic relationships and pedigrees.High-density genetic maps are constructed efficiently and quantitative trait loci for valuable traits are readily associated with positional candidate genes and/or converted into diagnostic tests for breeders.We understand the species,geographical,and genomic origins of domesticated apple more precisely,as well as its relationship to wild relatives.The WGS has turbo-charged application of these classical research steps to crop improvement and drives innovative methods to achieve more durable,environmentally sound,productive,and consumer-desirable apple production.This review includes examples of basic and practical breakthroughs and challenges in using the apple WGSs.Recommendations for“what’s next”focus on necessary upgrades to the genome sequence data pool,as well as for use of the data,to reach new frontiers in genomics-based scientific understanding of apple. | Cameron P.Peace Luca Bianco Michela Troggio Eric van de Weg Nicholas P.Howard Amandine Cornille Charles-Eric Durel Sean Myles ZoëMigicovsky Robert J.Schaffer Evelyne Costes Gennaro Fazio Hisayo Yamane Steve van Nocker Chris Gottschalk Fabrizio Costa David Chagné Xinzhong Zhang Andrea Patocchi Susan E.Gardiner Craig Hardner Satish Kumar Francois Laurens Etienne Bucher Dorrie Main Sook Jung Stijn Vanderzande | 2019 | Horticulture Research2019,6,1: | 3 |
| 9 | Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy显示文摘 | Zheng Z Wei Yan-Bing Zhu James Y Zhang Myles R McCrary Song Wang Yong-Bo Zhang Shan-Ping Yu Ling Wei | 2017 | Chinese Medical Journal2017,,19: | 3 |
| 10 | Capturing phraseology in an online dictionary for advanced users of English as a second language: a response to user needs显示文摘 | Janice McAlpine Johanne Myles | 2003 | System2003,,1: | 3 |
| 11 | Patterns of genomic and phenomic diversity in wine and table grapes显示文摘Grapes are one of the most economically and culturally important crops worldwide,and they have been bred for both winemaking and fresh consumption.Here we evaluate patterns of diversity across 33 phenotypes collected over a 17-year period from 580 table and wine grape accessions that belong to one of the world’s largest grape gene banks,the grape germplasm collection of the United States Department of Agriculture.We find that phenological events throughout the growing season are correlated,and quantify the marked difference in size between table and wine grapes.By pairing publicly available historical phenotype data with genome-wide polymorphism data,we identify large effect loci controlling traits that have been targeted during domestication and breeding,including hermaphroditism,lighter skin pigmentation and muscat aroma.Breeding for larger berries in table grapes was traditionally concentrated in geographic regions where Islam predominates and alcohol was prohibited,whereas wine grapes retained the ancestral smaller size that is more desirable for winemaking in predominantly Christian regions.We uncover a novel locus with a suggestive association with berry size that harbors a signature of positive selection for larger berries.Our results suggest that religious rules concerning alcohol consumption have had a marked impact on patterns of phenomic and genomic diversity in grapes. | ZoëMigicovsky Jason Sawler Kyle M Gardner Mallikarjuna K Aradhya Bernard H Prins Heidi R Schwaninger Carlos D Bustamante Edward S Buckler Gan-Yuan Zhong Patrick J Brown Sean Myles | 2017 | Horticulture Research2017,4,1: | 3 |
| 12 | Phase II trial of Sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer显示文摘 | Neelesh Sharma Nathan Pennell Myles Nickolich Balazs Halmos Patrick Ma Tarek Mekhail Pingfu Fu Afshin Dowlati | 2014 | Investigational New Drugs2014,,2: | 2 |
| 13 | Remifentanil, Fentanyl, and Cardiac Surgery: A Double-Blinded, Randomized, Controlled Trial of Costs and Outcomes显示文摘 | Paul S. Myles Jennifer O. Hunt Helen Fletcher Jennifer Watts David Bain Andrew Silvers Mark R. Buckland | 2002 | Anesthesia & Analgesia2002,,4: | 2 |
| 14 | Posttraumatic Stress Disorder in Aware Patients from the B-Aware Trial显示文摘 | Kate Leslie Matthew T. V. Chan Paul S. Myles Andrew Forbes Timothy J. McCulloch | 2010 | Anesthesia & Analgesia2010,,3: | 2 |
| 15 | Reactive and non-reactive transport modelling in partially water saturated argillaceous porous media around the ventilation experiment,Mont Terri显示文摘At Mont Terri Underground Research Laboratory (URL) Switzerland, a specific experiment has been performed in a tunnel, in order to investigate the hydro-mechano-chemical (HMC) perturbations induced in the argillaceous formation by forced ventilation. This experiment has been selected in the international project DECOVALEX to be used for process model development and validation. The numerical simulation of the geochemical response to the ventilation experiment (VE) is the object of the present paper, focusing on the transport of chloride as a conservative species and sulphate as a reactive species. Utilising the validated hydro-mechanical (HM) results from earlier steps of the DECOVALEX task, reactive and non-reactive transport models, incorporating the current understanding of the geochemistry at the site, were successfully constructed for the whole experimental period. The associated parametric and process uncertainty analyses clearly demonstrate that the basic HM understanding must be sound. However, to demonstrate this degree of robustness, the explicit inclusion of process representations of water desaturation, liquid vaporisation, species exclusion porosity, and redox processes, is required. | Alexander Bond Steven Benbow James Wilson Alain Millard Shigeo Nakama Myles English Christopher McDermott Benoit Garitte | 2013 | Journal of Rock Mechanics and Geotechnical Engineering2013,5,1: | 2 |
| 16 | Vitamin D Deficiency and Risk of Cardiovascular Disease显示文摘 | Thomas J. Wang Michael J. Pencina Sarah L. Booth Paul F. Jacques Erik Ingelsson Katherine Lanier Emelia J. Benjamin Ralph B. D?Agostino Myles Wolf Ramachandran S. Vasan | 2008 | Circulation2008,,4: | 2 |
| 17 | P250 Central nervous system (CNS) complications of ear nose throat (ENT) infections – case series显示文摘 | N. Vora P.D. Eunson K.K. Tallur A. Baxter R.A. Minns A.J.W. Steers L. Myles A.E. McLellan | 2009 | European Journal of Paediatric Neurology2009,,: | 2 |
| 18 | Renal cell carcinoma invading the urinary collecting system: implications for staging 显示文摘 | Uzzo RG Cherullo EE Myles J | 2002 | J Urol2002,167,6: | 1 |
| 19 | Obesity as an independent risk factor for inffectious morbidity in patients who undergo cesarean delivery显示文摘 | MYLES T D GOOCH J SANTOLAYA J | 2002 | Obstet Gynecol2002,100,51: | 1 |
| 20 | The Effect of Bispectral Index Monitoring on Long - Term Survival in the B - A- ware Trial显示文摘 | Leslie K Myles PS Forbes A | 2010 | Anesth Analg2010,110,3: | 1 |