tbuckley/cabot-search huggingface dataset:
Implications of Epigenetic Drift in Colorectal Neoplasia
Authors: Georg E. Luebeck, William D. Hazelton, Kit Curtius, Sean K. Maden, Ming Yu, Kelly T. Carter, Wynn Burke, Paul D. Lampe, Christopher I. Li, Cornelia M. Ulrich, Polly A. Newcomb, Maria Westerhoff, Andrew M. Kaz, Yanxin Luo, John M. Inadomi, William M. Grady
Journal: Cancer Research (2018)

Abstract Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here, we identify and validate 781 CpG islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples. However, compared with normal colon, this drift advanced (∼3–4-fold) faster in neoplasia, consistent with increased cell proliferation during neoplastic progression. The observed drift patterns were broadly consistent with modeled adenoma-to-carcinoma sojourn time distributions from colorectal cancer incidence data. These results support the hypothesis that, beginning with the founder premalignant cell, cancer precursors frequently sojourn for decades before turning into cancer, implying that the founder cell typically arises early in life. At least 77% to 89% of the observed drift variance in distal and rectal tumors was explained by stochastic variability associated with neoplastic progression, whereas only 55% of the variance was explained for proximal tumors. However, gene–CGI pairs in the proximal colon that underwent drift were significantly and primarily negatively correlated with cancer gene expression, suggesting that methylomic drift participates in the clonal evolution of colorectal cancer. Methylomic drift advanced in colorectal neoplasia, consistent with extended sojourn time distributions, which accounts for a significant fraction of epigenetic heterogeneity in colorectal cancer. Importantly, these estimated long-duration premalignant sojourn times suggest that early dietary and lifestyle interventions may be more effective than later changes in reducing colorectal cancer incidence. Significance: These findings present age-related methylomic drift in colorectal neoplasia as evidence that premalignant cells can persist for decades before becoming cancerous. See related commentary by Sapienza, p. 437
Is it time to radically change the two week wait (2WW) referral pathway for suspected brain and CNS cancer?
Authors: Mr Jing Xian Lee, Mr Anil Varma, Prof Philip Kane
Journal: Neuro-Oncology (2018)

In June 2015, the National Institute for Health and Care Excellence (NICE) published revised 2WW referral guidelines for general practitioners (GP) for patients with suspected brain and CNS cancer. The guidelines are comprehensive and include recommendations for using brain imaging and provision of relevant clinical information at referral. Retrospective audit of patients referred on 2WW pathway for suspected brain cancer to South Tees Trust between 1/7/2015 and 31/12/2017. Cases were identified from the Trust’s 2WW referral database. Data were collected from referral letters and patient records. Quality of referral information was assessed in 10 domains. 122 patients identified. 98 cases audited (50F:48M, median age 61 years, range 16–92 years). 24 cases excluded: non-brain/CNS 2WW referrals (n=12), spinal cases (n=9), records unavailable (n=3). 54 referrals were rejected as non-compliant under 2WW criteria: 30 with chronic symptoms, 20 with benign lesion/normal brain imaging. Compliance with referral information achieved 100% in 1 domain (patient contact details). Details of past medical history, medications, examination and allergies achieved 56–77% compliance. Details of performance status, social history and patient awareness of referral criteria achieved 2–8% compliance. Compliance with the NICE 2WW referral guidelines for brain &amp; CNS cancer is poor. The referral process involves considerable workload for clinical teams especially as 55% of referrals were found to be inappropriate. Compliance may be improved through educational programmes in primary care. Alternatively, by increasing GP access to early cranial imaging, the 2WW pathway could be decommissioned and replaced with a pathway whereby suspected malignancy reported on imaging is linked directly to the neuroscience MDT.
Relationship of the Rapid Shallow Breathing Index (RSBI) and capnography successfully at weaning
Authors: Ewerton Cousin, Elielton de Almeida Machado, Gustavo Dias Ferreira, Marilene Rabuske, Isadora Pisani, Márcio Osório Guerreiro, Rafael Bueno Orcy
Journal: Pulmonology (2018)
PTU-058 Audit of screening for hazardous alcohol intake of patients admitted with liver disease, and the implementation of an alcohol pathway
Authors: H Phillips, J Sinclair, L Grellier, H Gordon
Journal: Gut (2017)

Introduction  The 2013 NCEPOD report1 identified that care was ‘less than good` in more than half of cases reviewed for patients admitted with alcoholic liver related deaths, and that opportunities for diagnosis were missed on previous admissions. It was recommended that patients should be screened for hazardous drinking on admission with access to full assessment and brief intervention within 24 hours.  This is an audit of screening on admission, the implementation of a pathway and a reaudit.  The Wessex Academic Health Sciences Network (AHSN) funded this audit as part of a pathway improvement project for alcohol related liver disease.  Method  All patients admitted 1st January-31s March 2015, for at least 24 hours, coded with liver disease. The notes were reviewed for:  • Documentation of alcohol unit consumption,  • AUDIT – C use, if higher risk (AUDIT C>8), referral to the Alcohol Intervention Team (AIT)  • Reviewed by AIT  • Discharge support offered/referral to community services  • First or subsequent admission to hospital  • GP Communication/discharge summary  Following the first audit, an alcohol pathway was implemented, including an AIT electronic referral system, and supported by a Trust wide education programme, led by the AIT to improve alcohol history taking, and use of AUDIT-C.  The audit was repeated one year later 01/01/2016-31/03/2016.  Results  Conclusion  Trustwide training was effective in the use of AUDIT-C for screening for alcohol intake, with increased referrals to the AIT. Similar numbers of patients were seen by the AIT in both audits. Post discharge care was markedly improved in the 2016 audit. Ongoing training of staff is required with onward referral for those identified with harmful drinking. This audit has been repeated in other hospitals across Wessex and has been a springboard for change and improvement across the region  Reference  . National confidential enquiry into patient outcome and death, 2013, Alcohol Related Liver Disease: Measuring the Units (2013)  Disclosure of Interest  H Phillips Conflict with: Wessex AHSN, J. Sinclair: None Declared, L. Grellier: None Declared, H. Gordon: None Declared
Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic‐phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY
Authors: Rüdiger Hehlmann, Jorge E. Cortes, Teresa Zyczynski, Carlo Gambacorti‐Passerini, Stuart L. Goldberg, Michael J. Mauro, Mauricette Michallet, Bengt Simonsson, Loretta A. Williams, Srikanth Gajavelli, Irene DeGutis, Ginny P. Sen, Ron L. Paquette
Journal: American Journal of Hematology (2018)

SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor (TKI) use and management patterns in patients with chronic phase-chronic myeloid leukemia in the US and Europe in routine clinical practice. Herein we describe interruptions, discontinuations and switching of TKI therapy during the initial 2 years of treatment among 1121 patients prospectively enrolled between October 1, 2010 and March 7, 2017. Patient characteristics were broadly similar between the imatinib (n = 370), dasatinib (n = 376), and nilotinib (n = 375) cohorts. Treatment interruptions occurred in 16.4% (year 1) and 4.0% (year 2) of patients, mainly attributed to hematologic intolerances. Treatment discontinuations occurred in 21.8% (year 1) and 10.2% (year 2) of patients, with the highest rate within the first 3 months for intolerance. Switching of TKI was seen in 17.8% (year 1) and 9.5% (year 2) of patients. Significant associations were found between TKI switching and female gender (year 1), age ≥65 years at diagnosis (year 2) and treatment with imatinib (year 2). Intolerance was the most common reason given for patients discontinuing and for switching TKI therapy; however resistance was also cited. Lack of response monitoring in routine clinical practice may have resulted in lower identification of resistance in this dataset. Data from SIMPLICITY suggest that, in routine clinical practice, intolerance and resistance to TKIs influence decisions to change treatment. Changes in TKI therapy are frequent, with nearly a third of patients discontinuing their first-line TKI.
The impact of preprint on media reporting of science
Authors: Tom Sheldon
Journal: The Lancet (2018)

We note with interest that The Lancet has begun a trial of preprint submissions (June 23, p 2482).1Kleinert S, Horton R. Preprints with The Lancet: joining online research discussion platforms. Lancet 391: 2482–83.Google Scholar At the Science Media Centre we appreciate the potential benefits of preprint to the research process, but we are concerned about possible unforeseen effects on the public's understanding of science. Currently, reviewed and accepted research is released to journalists under embargo, allowing news outlets to publish simultaneously and giving reporters time to gather third party comment. In contrast, unverified preprint findings will appear instantly in the public domain. Journalists trawling the servers will struggle to tell the newsworthy and exciting from the poor and unsubstantiated, and no embargo means there will be no time to assess the claims. By the time erroneous claims are scrutinised (and perhaps demolished) by scientists, they could be published as fact in the daily news, to an unsuspecting readership of millions. Peer review is not perfect. The media don't always get it right either. But our existing system places checks and balances on both. If science is to embrace an exciting new approach, we urge the community to ensure it doesn't undermine measured and accurate communication of science. Preprint could bring great prizes, but, so far, consideration of its effects has focused almost exclusively on the gains to the research community. The public's understanding of evidence, valued so highly by scientists, is under threat if we get this wrong. The time to discuss the risks, and what we in the research community can do to minimise them, is now. I declare no competing interests. Preprints with The Lancet: joining online research discussion platformsFrom June, 2018, the Lancet family of journals are starting a 6-month trial in collaboration with the freely accessible preprint platform SSRN , which has been part of Elsevier since May, 2016. With this pilot, we are interested to see whether health and medical researchers are ready for this form of sharing work early in the research or publication process. Full-Text PDF
Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey
Authors: Nancy A Chow, Lalitha Gade, Sharon V Tsay, Kaitlin Forsberg, Jane A Greenko, Karen L Southwick, Patricia M Barrett, Janna L Kerins, Shawn R Lockhart, Tom M Chiller, Anastasia P Litvintseva, Eleanor Adams, Kerri Barton, Karlyn D Beer, Meghan L Bentz, Elizabeth L Berkow, Stephanie Black, Kristy K Bradley, Richard Brooks, Sudha Chaturvedi, Whitney Clegg, Melissa Cumming, Alfred DeMaria, Nychie Dotson, Erin Epson, Rafael Fernandez, Tara Fulton, Rebecca Greeley, Brendan Jackson, Alexander Kallen, Sarah Kemble, Monina Klevens, Randy Kuykendall, Ngoc H Le, Vivian Leung, Emily Lutterloh, Jarred Mcateer, Massimo Pacilli, Joyce Peterson, Monica Quinn, Kathleen Ross, Faye Rozwadowski, DJ Shannon, Kimberly A Skrobarcek, Snigdha Vallabhaneni, Rory Welsh, Yan Zhu
Journal: The Lancet Infectious Diseases (2018)
<i>Notes from the Field:</i> Multiple Cyclosporiasis Outbreaks — United States, 2018
Authors: Shannon M. Casillas, Carolyne Bennett, Anne Straily
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The 2018 outbreak season is noteworthy for multiple outbreaks of cyclosporiasis associated with different fresh produce items and the large number of reported cases. In 2018, two multistate outbreaks resulted in 761 laboratory-confirmed cases.
Abstract 13696: Very Long-Term (15-23 years) Outcomes of Bare Metal Stenting and Plain Old Balloon Angioplasty
Authors: Kyohei Yamaji, Takeshi Kimura, Katsumi Inoue, Shoichi Kuramitsu, Shinichi Shirai, Masashi Iwabuchi, Hiroyoshi Yokoi, Hideyuki Nosaka, Masakiyo Nobuyoshi
Journal: Circulation (2012)

Background: Target lesion revascularization (TLR) continued to occur beyond 4 years after the bare metal stent (BMS) implantation after an apparent plateau phase between 1 and 4 years. However, lon...
Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma
Authors: Laurent Garderet, Frederique Kuhnowski, Benoit Berge, Murielle Roussel, Martine Escoffre-Barbe, Ingrid Lafon, Thierry Facon, Xavier Leleu, Lionel Karlin, Aurore Perrot, Philippe Moreau, Gerald Marit, Anne-Marie Stoppa, Bruno Royer, Carine Chaleteix, Mourad Tiab, Carla Araujo, Pascal Lenain, Margaret Macro, Eric Voog, Lofti Benboubker, Olivier Allangba, Eric Jourdan, Frederique Orsini-Piocelle, Sabine Brechignac, Jean-Richard Eveillard, Karim Belhadj, Marc Wetterwald, Brigitte Pegourie, Arnaud Jaccard, Jean-Claude Eisenmann, Sylvie Glaisner, Mohamad Mohty, Cyrille Hulin, Herve Avet Loiseau, Claire Mathiot, Michel Attal
Journal: Blood (2018)
Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion
Authors: Qiang Fu, Le Xu, Yiwei Wang, Qi Jiang, Zheng Liu, Junyu Zhang, Quan Zhou, Han Zeng, Shanyou Tong, Tao Wang, Yangyang Qi, Baoying Hu, Hangcheng Fu, Huyang Xie, Lin Zhou, Yuan Chang, Yu Zhu, Bo Dai, Weijuan Zhang, Jiejie Xu
Journal: European Urology (2018)
Abstract 14505: Generation of Atherosclerosis in Mice via Somatic Deletion of Ldlr With AAV-CRISPR
Authors: Kelsey E Jarrett, Yi-Hsien Yeh, Rajat Gupta, Min Zhang, Ciaran M Lee, Perla Rodriguez, Henry J Pownall, Gang Bao, James F Martin, William R Lagor
Journal: Circulation (2016)

Introduction: Genetic studies of atherosclerosis in mice are both time-consuming and expensive. Mice knocked out for a gene of interest must be extensively backcrossed to C57BL/6J, and then bred to...
Association between ambient air pollution and daily hospital admissions for ischemic stroke: A nationwide time-series analysis
Authors: Yaohua Tian, Hui Liu, Zuolin Zhao, Xiao Xiang, Man Li, Juan Juan, Jing Song, Yaying Cao, Xiaowen Wang, Libo Chen, Chen Wei, Yonghua Hu, Pei Gao
Journal: PLoS Medicine (2018)

Background Evidence of the short-term effects of ambient air pollution on the risk of ischemic stroke in low- and middle-income countries is limited and inconsistent. We aimed to examine the associations between air pollution and daily hospital admissions for ischemic stroke in China. Methods and findings We identified hospital admissions for ischemic stroke in 2014–2016 from the national database covering up to 0.28 billion people who received Urban Employee Basic Medical Insurance (UEBMI) in China. We examined the associations between air pollution and daily ischemic stroke admission using a two-stage method. Poisson time-series regression models were firstly fitted to estimate the effects of air pollution in each city. Random-effects meta-analyses were then conducted to combine the estimates. Meta-regression models were applied to explore potential effect modifiers. More than 2 million hospital admissions for ischemic stroke were identified in 172 cities in China. In single-pollutant models, increases of 10 μg/m3 in particulate matter with aerodynamic diameter <2.5 μm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) and 1 mg/m3 in carbon monoxide (CO) concentrations were associated with 0.34% (95% confidence interval [CI], 0.20%–0.48%), 1.37% (1.05%–1.70%), 1.82% (1.45%–2.19%), 0.01% (−0.14%–0.16%), and 3.24% (2.05%–4.43%) increases in hospital admissions for ischemic stroke on the same day, respectively. SO2 and NO2 associations remained significant in two-pollutant models, but not PM2.5 and CO associations. The effect estimates were greater in cities with lower air pollutant levels and higher air temperatures, as well as in elderly subgroups. The main limitation of the present study was the unavailability of data on individual exposure to ambient air pollution. Conclusions As the first national study in China to systematically examine the associations between short-term exposure to ambient air pollution and ischemic stroke, our findings indicate that transient increase in air pollution levels may increase the risk of ischemic stroke, which may have significant public health implications for the reduction of ischemic stroke burden in China.
Corrigendum to “Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy” [Biomaterials 155C (2017) 25–40]
Authors: Guoyun Wan, Bowei Chen, Ling Li, Dan Wang, Shurui Shi, Tao Zhang, Yue Wang, Lianyun Zhang, Yinsong Wang
Journal: Biomaterials (2018)
Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting
Authors: Bhuvaneswari Krishnamoorthy, William R. Critchley, Alexander J. Thompson, Katherine Payne, Julie Morris, Rajamiyer V. Venkateswaran, Ann L. Caress, James E. Fildes, Nizar Yonan
Journal: Circulation (2017)

Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting.In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited. All veins were harvested by a single experienced practitioner. We randomly allocated 300 patients into closed tunnel CO2 EVH (n=100), open tunnel CO2 EVH (n=100), and traditional open vein harvesting (n=100) groups. The primary end point was endothelial integrity and muscular damage of the harvested vein. Secondary end points included clinical outcomes (major adverse cardiac events), use of healthcare resources, and impact on health status (quality-adjusted life-years).The open vein harvesting group demonstrated marginally better endothelial integrity in random samples (85% versus 88% versus 93% for closed tunnel EVH, open tunnel EVH, and open vein harvesting; P<0.001). Closed tunnel EVH displayed the lowest longitudinal hypertrophy (1% versus 13.5% versus 3%; P=0.001). However, no differences in endothelial stretching were observed between groups (37% versus 37% versus 31%; P=0.62). Secondary clinical outcomes demonstrated no significant differences in composite major adverse cardiac event scores at each time point up to 48 months. The quality-adjusted life-year gain per patient was 0.11 (P<0.001) for closed tunnel EVH and 0.07 (P=0.003) for open tunnel EVH compared with open vein harvesting. The likelihood of being cost-effective, at a predefined threshold of £20 000 per quality-adjusted life-year gained, was 75% for closed tunnel EVH, 19% for open tunnel EVH, and 6% for open vein harvesting.Our study demonstrates that harvesting techniques affect the integrity of different vein layers, albeit only slightly. Secondary outcomes suggest that histological findings do not directly contribute to major adverse cardiac event outcomes. Gains in health status were observed, and cost-effectiveness was better with closed tunnel EVH. High-level experience with endoscopic harvesting performed by a dedicated specialist practitioner gives optimal results comparable to those of open vein harvesting.URL: https://www.isrctn.com. International Standard Randomised Controlled Trial Registry Number: 91485426.
TCT-448: Scanning Electron Microscopic Observation of Coating Irregularities and Their Precursors in Unexpanded Durable Polymer-Based Drug-Eluting Stents
Authors: Mounir Basalus, Kenneth Tandjung, Hanim Sen, Thea Van Westen, Dirk Grijpma, Aart Van Apeldoorn, Clemens Von Birgelen
Journal: Journal of the American College of Cardiology (2011)
Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Authors: Melanie J. Davies, David A. D’Alessio, Judith Fradkin, Walter N. Kernan, Chantal Mathieu, Geltrude Mingrone, Peter Rossing, Apostolos Tsapas, Deborah J. Wexler, John B. Buse
Journal: Diabetes Care (2018)

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.