tbuckley/cabot-search huggingface dataset:
Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer
Authors: Filippo Pietrantonio, Rosalba Miceli, Alessandra Raimondi, Young Woo Kim, Won Ki Kang, Ruth E. Langley, Yoon Young Choi, Kyoung-Mee Kim, Matthew Guy Nankivell, Federica Morano, Andrew Wotherspoon, Nicola Valeri, Myeong-Cherl Kook, Ji Yeong An, Heike I. Grabsch, Giovanni Fucà, Sung Hoon Noh, Tae Sung Sohn, Sung Kim, Maria Di Bartolomeo, David Cunningham, Jeeyun Lee, Jae-Ho Cheong, Elizabeth Catherine Smyth
Journal: Journal of Clinical Oncology (2019)

In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value.
Cognition blindness and cognitive gadgets
Authors: Cecilia Heyes
Journal: Behavioral and Brain Sciences (2019)

Responding to commentaries from psychologists, neuroscientists, philosophers, and anthropologists, I clarify a central purpose of Cognitive Gadgets - to overcome "cognition blindness" in research on human evolution. I defend this purpose against Brunerian, extended mind, and niche construction critiques of computationalism - that is, views prioritising meaning over information, or asserting that behaviour and objects can be intrinsic parts of a thinking process. I argue that empirical evidence from cognitive science is needed to locate distinctively human cognitive mechanisms on the continuum between gadgets and instincts. Focussing on that requirement, I also address specific challenges, and applaud extensions and refinements, of the evidence surveyed in my book. It has been said that "a writer's idea of sound criticism is ten thousand words of closely reasoned adulation." I cannot disagree with this untraceable wag, but the 30 commentators on Cognitive Gadgets provided some 30,000 words of criticism that are of much greater scientific value than adulation. I am grateful to them all. The response that follows is V-shaped. It starts with the broadest conceptual and methodological issues and funnels down to matters arising from specific empirical studies.
Effects of <i>Helicobacter pylori</i> treatment and vitamin and garlic supplementation on gastric cancer incidence and mortality: follow-up of a randomized intervention trial
Authors: Wen-Qing Li, Jing-Yu Zhang, Jun-Ling Ma, Zhe-Xuan Li, Lian Zhang, Yang Zhang, Yang Guo, Tong Zhou, Ji-You Li, Lin Shen, Wei-Dong Liu, Zhong-Xiang Han, William J Blot, Mitchell H Gail, Kai-Feng Pan, Wei-Cheng You
Journal: BMJ (2019)

To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.Blinded randomized placebo controlled trial.Linqu County, Shandong province, China.3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease.151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease.H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.ClinicalTrials.gov NCT00339768.
British Society of Gastroenterology position statement on patient experience of GI endoscopy
Authors: Colin J Rees, Tim M Trebble, Christian Von Wagner, Zoe Clapham, Paul Hewitson, Hugh Barr, Simon Everett, Helen Griffiths, Manu Nayar, Kofi Oppong, Stuart Riley, John Stebbing, Siwan Thomas-Gibson, Roisin Bevan
Journal: Gut (2019)

We present the British Society of Gastroenterology (BSG) position statement on patient experience of GI endoscopy, recently published on the BSG website—www.bsg.org.uk/resource/patient-experience-of-gi-endoscopy-2019.html. The three dimensions of healthcare quality are patient safety, clinical effectiveness and patient experience, with much of healthcare practice focusing on the first two dimensions. Greater emphasis is now being given to the patient experience dimension in light of reports from Francis1 and Darzi2 highlighting the interaction between patient experience and quality of care. Clinical standards and safety in endoscopy are well reported and reviewed via the Joint Advisory Group on GI Endoscopy (JAG) accreditation programme. The Global Rating Scale3 used in JAG assessments includes a patient experience domain, but gives limited guidance available on how that should be measured or what standards should be …
Cell-specific translational profiling in acute kidney injury
Authors: Jing Liu, A. Michaela Krautzberger, Shannan H. Sui, Oliver M. Hofmann, Ying Chen, Manfred Baetscher, Ivica Grgic, Sanjeev Kumar, Benjamin D. Humphreys, Winston A. Hide, Andrew P. McMahon
Journal: Journal of Clinical Investigation (2014)
Changes in asthma mortality in England and Wales since 2001
Authors: Dominick E Shaw, Catherine M Gaynor, Andrew W Fogarty
Journal: Thorax (2019)

The number of deaths from asthma in England and Wales has not changed significantly over the last decade. This lack of improvement has received attention from both national asthma guidelines and the media. We examined asthma death data from the Office for National Statistics, stratified by age band. Every 5-year age band below the age of 80 years has seen a large reduction in mortality between 2001 and 2017, whereas numbers of asthma deaths have increased by 81% for people aged 80 years or above. This increase in older people dying from asthma requires explanation.
Ultrasmall Core-Shell Silica Nanoparticles for Precision Drug Delivery in a High-Grade Malignant Brain Tumor Model
Authors: Rupa Juthani, Brian Madajewski, Barney Yoo, Li Zhang, Pei-Ming Chen, Feng Chen, Melik Z. Turker, Kai Ma, Michael Overholtzer, Valerie A. Longo, Sean Carlin, Virginia Aragon-Sanabria, Jason Huse, Mithat Gonen, Pat Zanzonico, Charles M. Rudin, Ulrich Wiesner, Michelle S. Bradbury, Cameron W. Brennan
Journal: Clinical Cancer Research (2019)

Small-molecule inhibitors have revolutionized treatment of certain genomically defined solid cancers. Despite breakthroughs in treating systemic disease, central nervous system (CNS) metastatic progression is common, and advancements in treating CNS malignancies remain sparse. By improving drug penetration across a variably permeable blood-brain barrier and diffusion across intratumoral compartments, more uniform delivery and distribution can be achieved to enhance efficacy.Ultrasmall fluorescent core-shell silica nanoparticles, Cornell prime dots (C' dots), were functionalized with αv integrin-binding (cRGD), or nontargeting (cRAD) peptides, and PET labels (124I, 89Zr) to investigate the utility of dual-modality cRGD-C' dots for enhancing accumulation, distribution, and retention (ADR) in a genetically engineered mouse model of glioblastoma (mGBM). mGBMs were systemically treated with 124I-cRGD- or 124I-cRAD-C' dots and sacrificed at 3 and 96 hours, with concurrent intravital injections of FITC-dextran for mapping blood-brain barrier breakdown and the nuclear stain Hoechst. We further assessed target inhibition and ADR following attachment of dasatinib, creating nanoparticle-drug conjugates (Das-NDCs). Imaging findings were confirmed with ex vivo autoradiography, fluorescence microscopy, and p-S6RP IHC.Improvements in brain tumor delivery and penetration, as well as enhancement in the ADR, were observed following administration of integrin-targeted C' dots, as compared with a nontargeted control. Furthermore, attachment of the small-molecule inhibitor, dasatinib, led to its successful drug delivery throughout mGBM, demonstrated by downstream pathway inhibition.These results demonstrate that highly engineered C' dots are promising drug delivery vehicles capable of navigating the complex physiologic barriers observed in a clinically relevant brain tumor model.
A Step Forward Towards Cytomegalovirus Free Hematopoietic Stem Cell Transplantation
Authors: Alfaraj Abeer, Daniel R Reed, Gina Petroni, Sandra Monson, Paige Williams, Kathlene DeGregory, Leonid Volodin, Tamila L Kindwall-Keller, Karen K. Ballen
Journal: Blood (2018)
Nationwide analysis of treatment outcomes in children and adolescents routinely treated for tuberculosis in the Netherlands
Authors: Fajri Gafar, Natasha van't Boveneind-Vrubleuskaya, Onno W. Akkerman, Bob Wilffert, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2019)

As a vulnerable population, children and adolescents with tuberculosis (TB) are faced with many challenges, even those who live in low TB incidence countries. We aimed to evaluate factors associated with TB treatment outcomes allowing more focused interventions to support this population once diagnosed.A retrospective cohort study using a nationwide surveillance database was performed in children and adolescents (aged 0-18 years) treated for TB in the Netherlands from 1993 to 2018. Logistic regression analyses were used to estimate adjusted odds ratios (aOR) for associated factors of mortality and loss to follow-up (LTFU).Among 3253 eligible patients with known outcomes, 94.4% (95.9% children and 92.8% adolescents) were cured or completed treatment, 0.7% died during treatment and 4.9% were LTFU. There were no reported treatment failures. Risk factors of death included children aged 2-4 years (aOR 10.42), central nervous system TB (aOR 5.14), miliary TB (aOR 10.25), HIV co-infection (aOR 8.60), re-treated TB cases (aOR 10.12) and drug-induced liver injury (aOR 6.50). Active case-finding was a protective factor of death (aOR 0.13). Risk factors of LTFU were adolescents aged 15-18 years (aOR 1.91), illegal immigrants (aOR 4.28), urban domicile (aOR 1.59), unknown history of TB contact (aOR 1.99), drug-resistant TB (aOR 2.31), single adverse drug reaction (aOR 2.12), multiple adverse drug reactions (aOR 7.84) and treatment interruption >14 days (aOR 6.93). Treatment in recent years (aOR 0.94) and supervision by public health nurses (aOR 0.14) were protective factors of LTFU.Highly successful treatment outcomes were demonstrated in children and adolescents routinely treated for TB. Special attention should be given to specific risk groups to improve treatment outcomes.
Abstract 5166: Lysyl oxidase regulates cell surface EGFR, and directionality of cancer cell invasion
Authors: Haoran Tang, Caroline Springer, Richard Marais
Journal: Cancer Research (2018)

Abstract Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. We find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. A novel pharmacological inhibitor of LOX, CCT365623, disrupts EGFR cell surface retention in vitro and delays the growth of primary tumour cells in vivo. In addition to its role in controlling primary tumour growth, LOX expression is also implicated in the processes of cancer cell invasion, and thereby the process of metastasis. Notably, we find that when LOX is depleted or inhibited, cancer cells are no longer able to sence a chemo-attractive gradient, and invade in a directional manner. Importantly, LOX produced by both cancer cells and fibroblasts can mediate this behaviour. Together, we show that LOX regulates EGFR cell surface retention to drive tumour progression. We also find that LOX does not regulate cancer cell invasion per se, but rather that it regulates the directionality of cancer cell migration, and both the cancer and stromal cells appear to contribute to this behaviour. Citation Format: Haoran Tang, Caroline Springer, Richard Marais. Lysyl oxidase regulates cell surface EGFR, and directionality of cancer cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5166.
Isolation of Candida auris from invasive and non-invasive samples of a patient suffering from vascular disease, Italy, July 2019
Authors: Francesca Crea, Giulia Codda, Andrea Orsi, Alberto Battaglini, Daniele Roberto Giacobbe, Emanuele Delfino, Riccardo Ungaro, Anna Marchese
Journal: Eurosurveillance (2019)

We recently isolated Candida auris from a blood culture and cutaneous swabs of a patient in her mid-70s. Our routine phenotypic methods failed to identify the microorganism, but it was identified by molecular tests and MALDI-TOF MS analysis. Our report, the first from Italy, further underlines the geographically wide distribution of C. auris and the need to confirm species identification of any suspicious colony as soon as possible to stop its spread.
Achieving consensus on patient-reported outcome measures in clinical practice for inflammatory skin disorders
Authors: Lourdes Perez-Chada, Vanina L. Taliercio, Alice B. Gottlieb, Marta Van Beek, Kristina Callis Duffin, Margo Reeder, Joseph F. Merola, Robert A. Swerlick
Journal: Journal of the American Academy of Dermatology (2019)
High Prevalence of Severe Acute Malnutrition in Children with Sickle Cell Anemia over 5 Years of Age in Northern Nigeria
Authors: Djamila Labib Ghafuri, Shehu Umar Abdullahi, Najibah Aliyu Galadanci, Binta Jibir, Safiya Gambo, Halima Bello-Manga, Lawal Haliru, Khadija Bulama, Awwal Gambo, Muktar Aliyu, Brittany Covert, Adetola A. Kassim, Mark Rodeghier, Michael R. DeBaun
Journal: Blood (2017)
Inhalation Exposure Methodology
Authors: Robert F. Phalen, Richard C. Mannix, Robert T. Drew
Journal: Environmental Health Perspectives (1984)

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).
Enterotoxigenic Escherichia coli–blood group A interactions intensify diarrheal severity
Authors: Pardeep Kumar, F. Matthew Kuhlmann, Subhra Chakraborty, A. Louis Bourgeois, Jennifer Foulke-Abel, Brunda Tumala, Tim J. Vickers, David A. Sack, Barbara DeNearing, Clayton D. Harro, W. Shea Wright, Jeffrey C. Gildersleeve, Matthew A. Ciorba, Srikanth Santhanam, Chad K. Porter, Ramiro L. Gutierrez, Michael G. Prouty, Mark S. Riddle, Alexander Polino, Alaullah Sheikh, Mark Donowitz, James M. Fleckenstein
Journal: Journal of Clinical Investigation (2019)

by this group (1).The same images were used to demonstrate the presence of the A blood group in HT-29 cells.This experiment was repeated multiple times, and the authors are updating this panel with an independent replicate.The corrected panel appears below.
Translational genomics of nasopharyngeal cancer
Authors: Chi Man Tsang, Vivian Wai Yan Lui, Jeffrey P. Bruce, Trevor J. Pugh, Kwok Wai Lo
Journal: Seminars in Cancer Biology (2019)

Nasopharyngeal carcinoma (NPC), also named the Cantonese cancer, is a unique cancer with strong etiological association with infection of the Epstein-Barr virus (EBV). With particularly high prevalence in Southeast Asia, the involvement of EBV and genetic aberrations contributive to NPC tumorigenesis have remained unclear for decades. Recently, genomic analysis of NPC has defined it as a genetically homogeneous cancer, driven largely by NF-κB signaling caused by either somatic aberrations of NF-κB negative regulators or by overexpression of the latent membrane protein 1 (LMP1), an EBV viral oncoprotein. This represents a landmark finding of the NPC genome. Exome and RNA sequencing data from new EBV-positive NPC models also highlight the importance of PI3K pathway aberrations in NPC. We also realize for the first time that NPC mutational burden, mutational signatures, MAPK/PI3K aberrations, and MHC Class I gene aberrations, are prognostic for patient outcome. Together, these multiple genomic discoveries begin to shape the focus of NPC therapy development. Given the challenge of NF-κB targeting in human cancers, more innovative drug discovery approaches should be explored to target the unique atypical NF-κB activation feature of NPC. Our next decade of NPC research should focus on further identification of the -omic landscapes of recurrent and metastatic NPC, development of gene-based precision medicines, as well as large-scale drug screening with the newly developed and well-characterized EBV-positive NPC models. Focused preclinical and clinical investigations on these major directions may identify new and effective targeting strategies to further improve survival of NPC patients.
Medical Education 2020—Charting a Path Forward
Authors: Marianne Green, Diane B. Wayne, Eric G. Neilson
Journal: JAMA (2019)

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Kenneth Aubrey Stewart
Authors: John Sandford-Smith
Journal: BMJ (2019)

Kenneth Aubrey Stewart (always known as Aubrey) was born in Belfast on 10 August 1925 and died from old age on 6 April 2019, aged 93. He spent his childhood in Northern Ireland and obtained his medical degree at Queen’s University Belfast. After qualifying he came to England, decided on a career in anaesthesia, and rotated through various junior hospital posts. He did his national service in the Royal Air Force as an anaesthetist at RAF Hospital Ely, and completed his training as a senior registrar in Cardiff. Cardiff had one of the few academic units in the country at that time, but much more importantly, it was where Aubrey met his future wife, Susan, a physiotherapist, and they were married in 1960. That same year he was appointed as a consultant anaesthetist in Leicester. He worked at all the …
Evaluation of T Cell Compartment By Mass Cytometry Reveals Distinct Patterns of Expression of Exhaustion Markers in Chronic Lymphocytic Leukemia
Authors: Muharrem Muftuoglu, Li Li, Duncan Mak, Jared K Burks, Yuanxin Xi, Bingqian Hu, Hila Shaim, Nobuhiko Imahashi, Mustafa H Bdiwi, Juan Jimenez, Pinaki P Banerjee, Francesca Lorraine Wei Inng Lim, Lucila Nassif Kerbauy, Mecit Kaplan, April DePombo, Mayela Carolina Mendt, Rafet Basar, May Daher, David Costa Marin, Jing Wang, Michael Andreeff, William G Wierda, Nitin Jain, Philip A Thompson, Michael J. Keating, Darius Armstrong James, Richard E Champlin, Elizabeth J Shpall, Katayoun Rezvani
Journal: Blood (2017)
Abstract 12286: Appropriate Pharmacological Lipid Management in Patients With Angiographic Non-Obstructive Coronary Artery Disease (CAD)
Authors: Umar Rashid, Edris Alderwish, Nikhil Sharma, Rachel Gray, Prince Adam, Neil Coplan
Journal: Circulation (2018)

Introduction: Studies have shown that patients with non-obstructive CAD on angiography have an increased risk of cardiac events and benefit from preventive measures. Objectives: This study aims to ...