tbuckley/cabot-search huggingface dataset:
The Sea Inside
Authors: Aula Abbara
Journal: BMJ (2005)

The Sea Inside ‘Mar Adentro’ is based on the true story of Ramon Sampedro. Sampedro was quadriplegic and campaigned for 30 years for the right to end his own life. Javier Bardem gives an exquisite portrayal of Sampedro, a former ship's mechanic who broke his neck in a diving accident aged 23, and his central performance is one of the reasons this film works so well. For the past 30 years, he has been looked after by his brother Jose (Celso Bugallo) and his family while he pursues his legal case.



Sampedro's case caused controversy in Spain, a predominantly Catholic country, during his campaign. In 1998, a year after his legal case ended, he died mysteriously aged 55. Who helped him to die is still unknown. At this time, euthanasia is, in many countries, a contentious issue although neither Sampedro …
An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors
Authors: Martin Indarte, Roisin Puentes, Marco Maruggi, Nathan T. Ihle, Geoffrey Grandjean, Michael Scott, Zamal Ahmed, Emmanuelle J. Meuillet, Shuxing Zhang, Robert Lemos, Lei Du-Cuny, Fabiana I.A.L. Layng, Ricardo G. Correa, Laurie A. Bankston, Robert C. Liddington, Lynn Kirkpatrick, Garth Powis
Journal: Cancer Research (2019)

Abstract Cnk1 (connector enhancer of kinase suppressor of Ras 1) is a pleckstrin homology (PH) domain–containing scaffold protein that increases the efficiency of Ras signaling pathways, imparting efficiency and specificity to the response of cell proliferation, survival, and migration. Mutated KRAS (mut-KRAS) is the most common proto-oncogenic event, occurring in approximately 25% of human cancers and has no effective treatment. In this study, we show that selective inhibition of Cnk1 blocks growth and Raf/Mek/Erk, Rho and RalA/B signaling in mut-KRAS lung and colon cancer cells with little effect on wild-type (wt)-KRAS cells. Cnk1 inhibition decreased anchorage-independent mut-KRas cell growth more so than growth on plastic, without the partial "addiction" to mut-KRAS seen on plastic. The PH domain of Cnk1 bound with greater affinity to PtdIns(4,5)P2 than PtdIns(3,4,5)P3, and Cnk1 localized to areas of the plasma membranes rich in PtdIns, suggesting a role for the PH domain in the biological activity of Cnk1. Through molecular modeling and structural modification, we identified a compound PHT-7.3 that bound selectively to the PH domain of Cnk1, preventing plasma membrane colocalization with mut-KRas. PHT-7.3 inhibited mut-KRas, but not wild-type KRas cancer cell and tumor growth and signaling. Thus, the PH domain of Cnk1 is a druggable target whose inhibition selectively blocks mutant KRas activation, making Cnk1 an attractive therapeutic target in patients with mut-KRAS–driven cancer. Significance: These findings identify a therapeutic strategy to selectively block oncogenic KRas activity through the PH domain of Cnk1, which reduces its cell membrane binding, decreasing the efficiency of Ras signaling and tumor growth.
The Great Food Gamble
Authors: Andrew Moscrop
Journal: BMJ (2001)

We are on the brink of what could prove to be a medical catastrophe…. The superbugs are with us.” Ominous words from John Humphrys, voice of Radio Four's Today programme, Sunday Times columnist and, we now discover, one time Welsh dairy farmer and angry agriculturalist. In a readable book that seeks to expose and condemn the “effect of modern food production methods on our health,” Humphrys attributes the evolution of multidrug resistant “superbugs” partly to overprescribing, but mostly to the alarmingly liberal use of antibiotics in poultry farming.

Those of us in the medical profession may find references to a potential “medical catastrophe” …
Self-assembled green tea polyphenol-based coordination nanomaterials to improve chemotherapy efficacy by inhibition of carbonyl reductase 1
Authors: Lingling Shan, Guizhen Gao, Weiwei Wang, Wei Tang, Zhantong Wang, Zhen Yang, Wenpei Fan, Guizhi Zhu, Kefeng Zhai, Orit Jacobson, Yunlu Dai, Xiaoyuan Chen
Journal: Biomaterials (2019)
Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects
Authors: Luisa Klotz, Melanie Eschborn, Maren Lindner, Marie Liebmann, Martin Herold, Claudia Janoschka, Belén Torres Garrido, Andreas Schulte-Mecklenbeck, Catharina C. Gross, Johanna Breuer, Petra Hundehege, Vilmos Posevitz, Béatrice Pignolet, Giulia Nebel, Shirin Glander, Nicole Freise, Judith Austermann, Timo Wirth, Graham R. Campbell, Tilman Schneider-Hohendorf, Maria Eveslage, David Brassat, Nicholas Schwab, Karin Loser, Johannes Roth, Karin B. Busch, Monika Stoll, Don J. Mahad, Sven G. Meuth, Timothy Turner, Amit Bar-Or, Heinz Wiendl
Journal: Science Translational Medicine (2019)

Inhibition of a mitochondrial enzyme during multiple sclerosis treatment modulates antigen-specific T cell responses in an affinity-dependent fashion.
Psychological burden after 11 September tragedy
Authors: Kay Seong-Ngoo
Journal: BMJ (2002)

There is a substantial psychological impact among the residents of Manhattan after the 11 September terrorist attack in New York, according to an evaluation of psychosomatic disorders by a team of epidemiologists. They found many cases of acute post-traumatic stress disorder (PTSD) and depression after the unprecedented catastrophe. People directly exposed to the event are more likely to suffer from PTSD; victims with losses due to the tragedy are more vulnerable to ongoing depression.

About 3000 lives were lost, and many of those …
Urban airborne particle exposure impairs human lung and blood<i>Mycobacterium tuberculosis</i>immunity
Authors: Martha Torres, Claudia Carranza, Srijata Sarkar, Yolanda Gonzalez, Alvaro Osornio Vargas, Kathleen Black, Qingyu Meng, Raul Quintana-Belmares, Martha Hernandez, Jose Juan F Angeles Garcia, Victor Hugo Páramo-Figueroa, Marco Antonio Iñiguez-Garcia, Jose L Flores, Junfeng (Jim) Zhang, Carol R Gardner, Pamela Ohman-Strickland, Stephan Schwander
Journal: Thorax (2019)

Associations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored.To examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis.Cellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis.In vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1β production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC.Inhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.
Murder and Mayhem
Authors: Anja Weidmann
Journal: BMJ (2003)

If you want to know how dangerous it is to transport heroin in a swallowed condom, how many rhubarb leaves are needed to kill someone, or how mood cosmetics would look on a corpse, then Murder and Mayhem is the book for you.

The origins of this volume are, appropriately for a crime writer, rather convoluted. It all began with a suggestion from the past president of the south Californian chapter of the …
Engaging with society
Authors: Tiago Villanueva
Journal: BMJ (2008)

<b>Nazia Peer</b> is a medical doctor reading for a master of laws degree in the legal aspects of medical practice at Cardiff University. In 2006 she was awarded the Nelson Mandela scholarship, which recognises the leadership potential of young South Africans. She published her first novel, <i>House of Peace</i>, in 2005 and has written an award winning short story. <b>Tiago Villanueva</b> finds out more
FRI0034 Does heavy caffeine ingestion affect the efficacy of methotrexate
Authors: CM Silke, MS Murphy, S Busteed, TB Murphy, M Phelan, MG Molloy
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In a proportion of patients methotrexate (MTX) has to be withdrawn because of lack of efficacy or side effects. MTX results indirectly in increased adenosine release. Adenosine, acting at the A2 receptor, mediates the anti-inflammatory effects of MTX. Caffeine is a non selective adenosine receptor antagonist and reverses the anti-inflammatory effects of MTX in the rat adjuvant arthritis model. <h3>Objectives</h3> To see if there was any correlation between withdrawal of MTX due to treatment failure and caffeine ingestion. <h3>Methods</h3> Over a 10 month period 91 sequential patients in 2 centres who had ever been on MTX were interviewed. They were classified as either minimal or regular coffee drinkers dependant on whether they drank more or less than 7 cups of coffee per week. Concomitant theophyline medication and tea and cola ingestion were also documented. Doses used varied from 5 to 15 mg weekly (mean = 10.3 ± 2.75). <h3>Results</h3> The proportion of people who have to discontinue MTX is higher in those who are regular coffee drinkers (P value = 0.02). In this group the reason for discontinuing was due to treatment failure in 80% of cases. 90% of those still on MTX and 74% of those who discontinued MTX were minimal coffee drinkers. <h3>Conclusion</h3> Patients who are on MTX should decrease their caffeine intake as there is a statistically significant increase in treatment failure in those who drink coffee regularly. This may account for the reason that much higher doses of MTX are used in countries with a heavier caffeine consumption.
Medical student syndrome
Authors: Balaji Ravichandran
Journal: BMJ (2008)

After cramming Greek and Latin medical terms for a string of nights, relying heavily on midnight coffees and chastising myself for involuntary naps, I finished my first year theory exams satisfactorily. But the volatile information had almost completely evaporated by the time of my practical examinations, and I had to face the viva.

First was anatomy, and the external examiner began by asking, “When does the primary ossification centre of the first sternebra appear?” I was speechless. Naively, I thought that the questions in physiology and biochemistry at least …
Global appeal to focus on neglected diseases
Authors: Rhona MacDonald
Journal: BMJ (2005)

A global appeal to focus research on developing new drugs, diagnostic tests, and vaccines for tropical diseases affecting poor people in developing countries has been launched by a group of scientists and non-governmental organisations.

Led by an independent foundation, Drugs for Neglected Diseases Initiative (DNDi), the appeal was launched simultaneously in London, New Delhi, Nairobi, and Rio de Janeiro and was supported by Medecins Sans Frontieres (MSF) and Oxfam.

The appeal asks governments to make neglected diseases a research priority, ensure sustained financial support, and reduce patent and regulatory barriers in order to increase research and development activities for neglected diseases.

“The current system needs a fundamental overhaul to address …
Objective structured clinical examination
Authors: Vicky Mottram
Journal: BMJ (2000)

Or OSCE for short. The most barbaric examination ever invented since Madame Guillotine had her apprentices testing the equipment on each other to check their technique. I hate OSCEs. I hate them. Words have not been invented to express the depth of my loathing for this type of assessment. There is not a cell in my body that does not detest OSCEs. Even the 14 mites on each of my eyelashes sigh with relief at the ending of another OSCE ordeal. Is the theme of this article becoming clear?

For those of you yet to experience the delights offered by an OSCE, let me explain. The standard format consists of a circuit of a number of stations, …
London medical school implements admission test
Authors: Siddartha Dutta
Journal: BMJ (2004)

Royal Free and University College Medical School in London is set to follow the example of Oxford and Cambridge by adopting the Biomedical Admissions Test (BMAT) for the coming academic year.

The BMAT is a two hour test consisting of two multiple choice question papers and an essay section that tests aptitude and skills, scientific knowledge, and application and writing. Prospective medical students have to sit the exam at one of the designated UK or international open centres, and the results are distributed to the universities.

“With the huge volume of applications we have now it is very difficult to be objective about who we should select for the interview places we have. The personal statements are becoming formulaic. A levels are all predicted A grades and the references are no longer confidential so they are less useful,” said …
The role of estrogen receptor subtypes in ovarian hormonal therapy
Authors: Na Wei, Karen Chan, Stephanie Liu, Kelvin Chan, Rebecca Leung, Hextan Ngan
Journal: Cancer Research (2007)

3272  Estrogen, a steroid hormone mainly synthesized in the ovary, regulates the expression of genes that are responsible for cell proliferation, apoptosis, tumor metastasis and invasion. The effects of estrogen are mediated through estrogen receptors (ER). Previous investigations demonstrated that two major subtypes of ER (α and β) had opposing effects on cell proliferation: ERα promoted cell proliferation, whereas ERβ induced cell apoptosis. Although ovarian cells bear hormone receptors and are hormone sensitive, hormonal therapy in ovarian cancer is not well established. The relationship between cellular responses to hormonal therapy and the expressions of estrogen receptor subtypes is still unclear.  The aim of this study was to investigate the cellular responses of ovarian cancer to selective estrogen receptor modulators in relation to estrogen receptor subtypes expressions. In this study, the effects of a spectrum of estrogen receptor agonist, partial agonist and a newly discovered pure antagonist on the growth of ovarian cancer cells bearing different estrogen receptor subtypes were studied. Using Real-time PCR, we found that 41.6% of ovarian cancer cell lines (5 of 12) showed higher ERα than ERβ mRNA levels (ERα/ERβ ratio>1) whereas all seven normal ovarian cell lines showed higher ERβ levels. Four ovarian cancer cell lines with different expression profiles (ERα+/ERβ+, ERα-/ERβ-, ERα-/ERβ+, ERα+/ERβ-) were selected. Apoptosis and clonogenic assays were used to detect the effects of drugs on cell apoptosis and proliferation respectively. Estradiol (agonist) significantly reduced apoptosis and increased survival of α+/β+ and α+/β- cells, but it had no effect on α-/β- or α-/β+ cells, implying that Estradiol promoted the growth of ovarian cancer cells bearing the ERα receptor subtype. Fulvestrant (pure antagonist) increased apoptosis and reduced survival in all four different cell lines, suggesting that its effects were mediated via a receptor-independent pathway. Tamoxifen (partial agonist) induced apoptosis of α+/β- and α-/β+ cells at different concentrations, but had no effect on α+/β+ and α-/β-cells, suggesting Tamoxifen might have a partial agonist effect on ERα positive cells but a pure antagonist effect on ERβ positive cells. These findings provided some insights into the use of hormonal therapy in ovarian cancer patients with different estrogen receptor subtypes expression profiles.
How much water an Airbus can buy
Authors: Ben Lawton
Journal: BMJ (2004)

Oscar Wilde reputedly lay on his death bed sipping vintage champagne. When asked why, he replied, “Isn't it obvious? I'm dying beyond my means.” Sixty years before, Wilde's father was training at Moorfields Eye Hospital in London, just around the corner from John Snow. Snow beat Hippocrates to the title of greatest doctor ever in Hospital Doctor 's 2003 survey. Snow famously removed the …
Association of Socioeconomic Status and Brain Injury With Neurodevelopmental Outcomes of Very Preterm Children
Authors: Isabel Benavente-Fernández, Anne Synnes, Ruth E. Grunau, Vann Chau, Chantel Ramraj, Torin Glass, Dalit Cayam-Rand, Arjumand Siddiqi, Steven P. Miller
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Studies of socioeconomic status and neurodevelopmental outcome in very preterm neonates have not sensitively accounted for brain injury. <h3>Objective</h3> To determine the association of brain injury and maternal education with motor and cognitive outcomes at age 4.5 years in very preterm neonates. <h3>Design, Setting, and Participants</h3> Prospective cohort study of preterm neonates (24-32 weeks’ gestation) recruited August 16, 2006, to September 9, 2013, at British Columbia Women's Hospital in Vancouver, Canada. Analysis of 4.5-year outcome was performed in 2018. <h3>Main Outcomes and Measures</h3> At age 4.5 years, full-scale IQ assessed using the Wechsler Primary and Preschool Scale of Intelligence, Fourth Edition, and motor outcome by the percentile score on the Movement Assessment Battery for Children, Second Edition. <h3>Results</h3> Of 226 survivors, neurodevelopmental outcome was assessed in 170 (80 [47.1%] female). Based on the best model to assess full-scale IQ accounting for gestational age, standardized β coefficients demonstrated the effect size of maternal education (standardized β = 0.21) was similar to that of white matter injury volume (standardized β = 0.23) and intraventricular hemorrhage (standardized β = 0.23). The observed and predicted cognitive scores in preterm children born to mothers with postgraduate education did not differ in those with and without brain injury. The best-performing model to assess for motor outcome accounting for gestational age included being small for gestational age, severe intraventricular hemorrhage, white matter injury volume, and chronic lung disease. <h3>Conclusions and Relevance</h3> At preschool age, cognitive outcome was comparably associated with maternal education and neonatal brain injury. The association of brain injury with poorer cognition was attenuated in children born to mothers of higher education level, suggesting opportunities to promote optimal outcomes.
Midwives, mothers and medical students
Authors: Omer Aziz
Journal: BMJ (1999)

During the past five years of medical school, I can recall facing numerous new but strange situations. One such occasion was during my first week of obstetrics as a medical student. I was just three months into my first clinical year and, having just completed six weeks of medicine and six weeks of surgery, had been given the challenge of mastering “obs and gynae.” My ignorance at the time was such that I did not even know the difference between the two. On top of this, by some perverse twist of fate, I was to be the first medical student “on call” in the labour ward. Looking back, it is terrifying to think how I was thrown into the deep end, but at the time I didn't quite know what to expect.

I stepped into the labour ward for the first time and immediately noticed the moist, warm atmosphere. The heavy air around me soon filled my nose and …
Stiff: the Curious Lives of Human Cadavers
Authors: Stephen Ginn
Journal: BMJ (2004)

I have spent the past few years deeply embroiled in the study of how to prevent Londoners from dying. But I have never devoted much time to wondering what happens to their remains once they are actually dead. Nevertheless, human remains have something morbidly interesting about them, and this subject provides American journalist Mary Roach with more than enough material for her fascinating book.

Many people donate their bodies to science with …
The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells
Authors: Tamilla Nechiporuk, Stephen E. Kurtz, Olga Nikolova, Tingting Liu, Courtney L. Jones, Angelo D'Alessandro, Rachel Culp-Hill, Amanda d'Almeida, Sunil K. Joshi, Mara Rosenberg, Cristina E. Tognon, Alexey V. Danilov, Brian J. Druker, Bill H. Chang, Shannon K McWeeney, Jeffrey W. Tyner
Journal: Cancer Discovery (2019)

Abstract To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen to identify gene knockouts resulting in drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results in venetoclax resistance in AML cell lines. Resistance to venetoclax resulted from an inability to execute apoptosis driven by BAX loss, decreased expression of BCL2, and/or reliance on alternative BCL2 family members such as BCL2L1. The resistance was accompanied by changes in mitochondrial homeostasis and cellular metabolism. Evaluation of TP53 knockout cells for sensitivities to a panel of small-molecule inhibitors revealed a gain of sensitivity to TRK inhibitors. We relate these observations to patient drug responses and gene expression in the Beat AML dataset. Our results implicate TP53, the apoptotic network, and mitochondrial functionality as drivers of venetoclax response in AML and suggest strategies to overcome resistance. Significance: AML is challenging to treat due to its heterogeneity, and single-agent therapies have universally failed, prompting a need for innovative drug combinations. We used a genetic approach to identify genes whose inactivation contributes to drug resistance as a means of forming preferred drug combinations to improve AML treatment. See related commentary by Savona and Rathmell, p. 831. This article is highlighted in the In This Issue feature, p. 813
Television: Surgery Live
Authors: Emily Pull
Journal: BMJ (2009)

“If anyone feels ill at any time, please close your eyes for a couple of minutes.” Channel 4’s series of programmes showing live surgery began with this rather ominous introduction. Most medical students’ experience is of hours of standing around operating theatres waiting for the patient to be prepared and the surgeon to arrive. Viewing the best bits of an operation in a one hour slot from a comfortable chair has rather more appeal. With a studio audience at the Wellcome Collection in London, a live relay …