tbuckley/cabot-search huggingface dataset:
Small Molecule KRAS Agonist for Mutant KRAS Cancer Therapy
Authors: Ke Xu, Dongkyoo Park, Andrew T. Magis, Jun Zhang, Wei Zhou, Gabriel L. Sica, Suresh S. Ramalingam, Walter J. Curran, Xingming Deng
Journal: Molecular Cancer (2019)

Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer. Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer cells with KRA-533 resulted in increased KRAS activity and suppression of cell growth. Lung cancer cell lines with KRAS mutation were relatively more sensitive to KRA-533 than cell lines without KRAS mutation. Mutating one of the hydrogen-bonds among the KRA-533 binding amino acids in KRAS (mutant K117A) resulted in failure of KRAS to bind KRA-533. KRA-533 had no effect on the activity of K117A mutant KRAS, suggesting that KRA-533 binding to K117 is required for KRA-533 to enhance KRAS activity. Intriguingly, KRA-533-mediated KRAS activation not only promoted apoptosis but also autophagic cell death. In mutant KRAS lung cancer xenografts and genetically engineered mutant KRAS-driven lung cancer models, KRA-533 suppressed malignant growth without significant toxicity to normal tissues. The development of this KRAS agonist as a new class of anticancer drug offers a potentially effective strategy for the treatment of lung cancer with KRAS mutation and/or mutant KRAS-driven lung cancer.
National Estimates of e-Cigarette Use Among Pregnant and Nonpregnant Women of Reproductive Age in the United States, 2014-2017
Authors: Buyun Liu, Guifeng Xu, Shuang Rong, Donna A. Santillan, Mark K. Santillan, Linda G. Snetselaar, Wei Bao
Journal: JAMA Pediatrics (2019)

This review of data from the National Health Interview Survey compares the prevalence of conventional and e-cigarette use between pregnant women and nonpregnant women in the same age group in the United States.
The Anatomy of Disgust
Authors: Ben Mills
Journal: BMJ (2000)

Disgust is an every. day experience (last night's dishes look pretty disgusting piled up in he sink, and the overnight arrivals in the cat litter tray made a good attempt at putting me off my breakfast this morning). Miller's excellent book plunges us into the minutiae of all things disgusting in an attempt to find the causes and effects of this universal experience. With examples from psychology, sociology, and literature, both ancient and modern, Miller raises a wide range of points throughout his …
BMA does not support shortening medical training
Authors: Helen Barratt
Journal: BMJ (2001)

Further research is needed before the BMA will endorse the shortening of medical degree courses. In a new report, the association explores the provision of shortened degree courses and concludes that a full evaluation is needed before any changes are made.

The government's NHS Plan for England published last year proposed a one year reduction in the length of both the graduate and undergraduate medical courses in order to address …
Lifestyles of medical students in Jerusalem are “shocking”
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2002)

The faculty of the Hebrew University Hadassah Medical School in Jerusalem was caught with their stethoscopes down after a survey showed that most new graduates don't practise what they're supposed to preach. Their smoking prevalence (25%) is only slightly less that that of the general population (28%), and most new graduates take little or no physical exercise.



Most said that during their six years of medical studies, none or only a few of their teachers had advised them to stop smoking or to exercise. Of the Jerusalem medical school graduates surveyed, 67% thought the school should intensify its teaching of these subjects.

A graduate of the medical school, Dr Tal Haimov, surveyed 83 of his 110 peers after being shocked …
GKT computer loss
Authors: Alex Brooks
Journal: BMJ (1999)

An invitation to thieves?



Computer chips worth £40 000-50 000 have been stolen from Guy's, King's and St Thomas's (GKT) Medical School's New Hunt's House, just as it was preparing to open its doors to students for the first time.

A spokesman from King's College London confirmed that “the chips from 120 … brand new Dell computers in open access rooms … were removed by thieves in mid September.” They were taken from the Guy's campus of GKT. A spokesperson …
Abstract 19: Cardiopulmonary Resuscitation by Bystanders with Chest Compressions Only for Children with Witnessed Out-of-Hospital Cardiac Arrest
Authors: Naoki Shimizu, Kunio Ohta, Masahiko Nitta, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura, None Japanese Paediatric Resuscitation Study (PReSS) Group, None JCS-ReSS group
Journal: Circulation (2012)

Background: Conventional cardiopulmonary resuscitation (CPR) is a barrier to bystanders including parents doing CPR for children. Particularly mouth-to-mouth ventilation has been considered to be difficult to teach and perform. Several clinical studies have shown the efficacy of bystander CPR by chest compression only (CC-only) for adults, but not yet stated enough for children. Methods: In a nationwide out-of-hospital cardiac arrest (OHCA) registration from 2005 to 2010, we enrolled 11,417 children aged less than 18 years old. Data collected include age, etiology, ECG wave form, type of CPR, and neurological outcome. Favorable outcome was defined as cerebral performance category 1 or 2. Results: 3,486 (31%) children with OHCA were described as cardiac etiology, and 7,931 (69%) as non-cardiac. VF/pulseless VT (VF/pVT) in 546 (5%) cases, PEA in 1,668 (15%), and asystole in 8,168 (71%). 3,041 (27%) cases received conventional CPR, 2,421 (21%) received CC-only CPR, and 5,507 (48%) were given no CPR. Within 2,808 (25%) children with witnessed citizen bystanders, 706 (25% of 2,808) received conventional CPR and 577 (21% of 2,808) received CC-only CPR, but outcome was not available in 69 cases. Any CPR comparing with no CPR (8.5% [463/5,462] vs 3.1% [168/5,507]; OR 2.78, 2.32-3.32), or conventional CPR comparing with CC-only (11% [329/3,041] vs 5.5% [134/2,421]; OR 1.95, 1.59-2.40) showed higher favorable outcomes. However, analysis in children with witnessed citizen bystanders revealed no difference on favorable outcome between conventional CPR and CC-only CPR (9.0% [60/668] vs 7.5% [41/546]; OR 1.22, 0.80-1.83). In each waveform group (VF/pVT; 32% [38/118] vs 29% [25/86]; OR 1.11, 0.62-1.97, PEA 7.1% [11/156] vs 6.3% [9/142]; OR 1.11, 0.45-2.76, Asystole 3.1% [11/353] vs 2.2% [7/318]; OR 1.42, 0.54-3.69), even excluding infants (11% [56/514] vs 8.0% [35/438]; OR 1.36, 0.88-2.11), indicated same trends. Conclusion: CC-only CPR by witnessed citizen is equally effective for children who have witnessed OHCA, comparing with conventional CPR. Enhancement of citizen bystander CPR including children with uniform BLS algorithm is reasonable, and need to be enriched further to diminish paediatric OHCA events without bystander CPR.
Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: a self-controlled case series study using data from the Clinical Practice Research Datalink
Authors: Georgina Nakafero, Matthew J Grainge, Puja R Myles, Christian D Mallen, Weiya Zhang, Michael Doherty, Jonathan S Nguyen-Van-Tam, Abhishek Abhishek
Journal: Annals of the Rheumatic Diseases (2019)

Objectives To examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs). Methods We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1–14 days prevaccination and 0–14, 15–30, 31–60 and 61–90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated. Results Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)). Conclusion This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs.
Outcomes of liver transplantation for non-alcoholic steatohepatitis: A European Liver Transplant Registry study
Authors: Debashis Haldar, Barbara Kern, James Hodson, Matthew James Armstrong, Rene Adam, Gabriela Berlakovich, Josef Fritz, Benedikt Feurstein, Wolfgang Popp, Vincent Karam, Paolo Muiesan, John O'Grady, Neville Jamieson, Stephen J. Wigmore, Jacques Pirenne, Seyed Ali Malek-Hosseini, Ernest Hidalgo, Yaman Tokat, Andreas Paul, Johann Pratschke, Michael Bartels, Pavel Trunecka, Utz Settmacher, Massimo Pinzani, Christophe Duvoux, Philip Noel Newsome, Stefan Schneeberger
Journal: Journal of Hepatology (2019)

<h3>Background & Aims</h3> Little is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors. <h3>Methods</h3> We analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival. <h3>Results</h3> Among 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH – an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, <i>p <</i>0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, <i>p =</i> 0.713) or grafts (HR 0.99; <i>p =</i> 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61–65 years: HR 2.07, <i>p <</i>0.001; >65: HR 1.72, <i>p =</i> 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, <i>p</i> = 0.048) and low (<18.5 kg/m<sup>2</sup>: HR 4.29, <i>p</i> = 0.048) or high (>40 kg/m<sup>2</sup>: HR 1.96, <i>p</i> = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors. <h3>Conclusions</h3> The number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications. <h3>Lay summary</h3> The prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.
Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data
Authors: John M Dennis, Beverley M Shields, William E Henley, Angus G Jones, Andrew T Hattersley
Journal: The Lancet Diabetes & Endocrinology (2019)

BackgroundResearch using data-driven cluster analysis has proposed five subgroups of diabetes with differences in diabetes progression and risk of complications. We aimed to compare the clinical utility of this subgroup-based approach for predicting patient outcomes with an alternative strategy of developing models for each outcome using simple patient characteristics.MethodsWe identified five clusters in the ADOPT trial (n=4351) using the same data-driven cluster analysis as reported by Ahlqvist and colleagues. Differences between clusters in glycaemic and renal progression were investigated and contrasted with stratification using simple continuous clinical features (age at diagnosis for glycaemic progression and baseline renal function for renal progression). We compared the effectiveness of a strategy of selecting glucose-lowering therapy using clusters with one combining simple clinical features (sex, BMI, age at diagnosis, baseline HbA1c) in an independent trial cohort (RECORD [n=4447]).FindingsClusters identified in trial data were similar to those described in the original study by Ahlqvist and colleagues. Clusters showed differences in glycaemic progression, but a model using age at diagnosis alone explained a similar amount of variation in progression. We found differences in incidence of chronic kidney disease between clusters; however, estimated glomerular filtration rate at baseline was a better predictor of time to chronic kidney disease. Clusters differed in glycaemic response, with a particular benefit for thiazolidinediones in patients in the severe insulin-resistant diabetes cluster and for sulfonylureas in patients in the mild age-related diabetes cluster. However, simple clinical features outperformed clusters to select therapy for individual patients.InterpretationThe proposed data-driven clusters differ in diabetes progression and treatment response, but models that are based on simple continuous clinical features are more useful to stratify patients. This finding suggests that precision medicine in type 2 diabetes is likely to have most clinical utility if it is based on an approach of using specific phenotypic measures to predict specific outcomes, rather than assigning patients to subgroups.FundingUK Medical Research Council.
Superiority of Avatrombopag to Placebo in Increasing Platelet Counts in Patients with Chronic Liver Disease-Associated Thrombocytopenia Undergoing Scheduled Procedures: Results from 2, Phase 3 Randomized Studies
Authors: Norah Terrault, David J Kuter, Namiki Izumi, Zeid Kayali, Paul Mitrut, Won Young Tak, Francesco Bibbiani
Journal: Blood (2017)
Medical student forums
Authors: Matas Morkevicius
Journal: BMJ (2005)

The internet is becoming one of the most important means of international communication. Medical student forums give students from different cultural backgrounds the opportunity to exchange their ideas and share their experiences about how to survive medical school.



The Student Doctor Network Forum at www.forums.studentdoctor.net is one of the most popular medical student discussion forums, which boasts more then 150 000 posts. This includes discussions on textbooks, suggestions on how to do well on …
A boot shaped heart
Authors: Najindra Maharjan, Subarna Mani Acharya
Journal: BMJ (2006)

An 18 month old female child presented with a history of dyspnoea on exertion. She often gets cyanosed after feeding or crying and sometimes becomes apnoeic. On examination, there was cyanosis and digital clubbing. Auscultation of the heart showed a loud ejection systolic murmur in the pulmonary area. Her chest x ray film is shown in fig 1.
Academic teaching staff face redundancy at British universities
Authors: Helen Barratt
Journal: BMJ (2002)

Many university lecturers in the United Kingdom are facing redundancy, as higher education institutions are forced to axe jobs, after budget cuts and falls in the number of students on some courses. According to a recent report in the Guardian ,1 medical schools could be some of the worst hit, along with engineering, social sciences, and modern languages departments.

The BMA is particularly …
Picture Quiz: A comma in the colon
Authors: Stephen J Goldie, Christopher Wilson
Journal: BMJ (2003)

You are on a surgical firm, when a call comes through from a local general practitioner regarding one of his patients whom he is sending urgently to the emergency department by ambulance. The patient is a 43 year old woman, who presented this morning with sudden onset of severe abdominal pain. The pain is diffuse, constant in nature, and associated with nausea and vomiting. Initially, the patient had diarrhoea, but has now developed complete constipation. On examination she has pyrexia, tachycardia, and a rigid abdomen. The white cell count and inflammatory markers are raised. When the patient was 3 months old she had an operation for intussusception. Fifteen years ago she had a similar episode and at laparotomy, bowel obstruction secondary to adhesions was diagnosed--approximately 20 cm of small bowel was removed. She has been fit and healthy since. When you meet the woman in the emergency …
Zenkerʼs diverticulum peroral endoscopic myotomy using a scissors-type knife
Authors: Seyma Bahsi, Nigar Rustemova, Kia Vosoughi, Yervant Ichkhanian, Tossapol Kerdsirichairat, Juliana Yang, Mouen A. Khashab
Journal: Endoscopy (2019)

Zenker's diverticulum is a rare anatomic defect characterized by herniation of the hypopharyngeal mucosa between the inferior aspect of the inferior constrictor muscle and the cricopharyngeus muscle. Most patients are elderly and present with symptoms of dysphagia, regurgitation, chronic cough, aspiration, and weight loss [1]. The treatment of symptomatic Zenker's diverticulum has evolved from open surgical approaches to minimally invasive endoscopic procedures [2].
From disc jockey to breast surgeon
Authors: Xanthe M Barkla, Timothy Michael Brock
Journal: BMJ (2007)

<b>Mike Dixon</b> is head of the Edinburgh Breast Unit, which treats 750 cases a year of women with newly diagnosed breast cancers. He is a consultant surgeon and a lecturer in surgery. He has published more than 200 papers and written or edited more than 15 books. He was the editor of the journal <i>Breast</i>, from its inception in 1992 to 2001, and was on the editorial board of the <i>BMJ</i>. <b>Xanthe Barkla</b> and <b>Timothy Brock</b> caught up with him
Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia
Authors: Juan Jimenez-Cauhe, David Saceda-Corralo, Rita Rodrigues-Barata, Angela Hermosa-Gelbard, Oscar M. Moreno-Arrones, Diego Fernandez-Nieto, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2019)
Incorporating health promotion into history taking
Authors: Brian R W McMillan
Journal: BMJ (2008)

Before becoming a medical student I worked as a health psychologist. This involved trying to explain what motivates the behaviours associated with health and illness. Medical training has steered me towards diagnosis and treatment, but perhaps there is room for more communication between these two disciplines.



When taking histories many doctors do not routinely ask patients if they have considered a change in a behaviour that may play a part in their current illness and future health. Is this because we do not feel it is our role or because we do not have time? …
Video Casebook: Medicine - the Toy Boy and the Burgundy Car
Authors: Lok Bin Yap
Journal: BMJ (2000)

This book's distinctive feature is the CD Rom that comes with it. It comprises 50 cases, along with 15-second video clips of patients describing their symptoms on the CD. Notes and five multiple choice questions are included for each of the cases. The questions are also laid out on the CD, but the notes relevant …
Abstract 17962: Prognostic Value of Diuretic Resistance in Patients Admitted for Acute Decompensated Heart Failure With Reduced and Preserved Left Ventricular Ejection Fraction:A Prospective Study
Authors: Eiji Fukuhara, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Makoto Abe, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2017)

Background: The reduced diuretic response is associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). However, the pathophysiologic importance of inadequatel...
Delivering a STINGing Blow to Small Cell Lung Cancer via Synergistic Inhibition of DNA-Damage Response and Immune-Checkpoint Pathways
Authors: Joseph B. Hiatt, David MacPherson
Journal: Cancer Discovery (2019)

Abstract Summary: Small cell lung cancer (SCLC) has demonstrated modest responses to immune-checkpoint blockade despite harboring a high mutational burden. In this issue, Sen and colleagues show remarkable synergy between inhibition of the DNA-damage response and the PD-1 axis, resulting in striking tumor regressions in SCLC mouse models. See related article by Sen et al., p. 646.
From the Edge of the Couch
Authors: Rabia Malik
Journal: BMJ (2003)

“Bizarre psychiatric cases and what they teach us about ourselves” is what Persaud claims his book is all about. In a collection of case histories combined with some historical perspectives on mental illness and commentary, Persaud explores some truly bizarre conditions. From werewolves to witches and folie a deux to phantom lover syndrome, with other extreme delusions and obsessions along the way, you are not likely …
Abstract 16898: Echo-Guided Pericardiocentesis Management of Hemopericardium: 10-year Review of Experience
Authors: Annop Lekhakul, Eric R Fenstad, Chalailak Assawakawintip, Sorin V Pislaru, Assefa M Ayalew, Joseph F Maalouf, Vuyi Nkomo, Jeremy Thaden, Jae K Oh, Larry J Sinak, Garvan C Kane
Journal: Circulation (2017)

Introduction: As invasive cardiovascular care becomes increasingly complex, cardiac perforation leading to hemopericardium is an increasingly prevalent complication. We sought to assess the frequen...
My patients need me
Authors: Carl Morris
Journal: BMJ (1999)

“All healthcare workers have a pathological need to be needed.” I'm not sure where I heard that, but I find a lot of truth in it. It explains why we are all so happy to give up fairly important things - having a life, for example - in return for the opportunity to run down corridors with a serious expression and a white coat on. We actually enjoy it.

I suppose you could describe any career choice as a sickness, whether it's a need for money, travel, or whatever. But in medicine I think it is a particularly useful idea as it does much to redress the imbalance of power between the professional and the patient. Both have a need for the other. It belies the myth of …