tbuckley/cabot-search huggingface dataset:
Prospective Blinded Study of <i>BRAF</i>V600E Mutation Detection in Cell-Free DNA of Patients with Systemic Histiocytic Disorders
Authors: David M. Hyman, Eli L. Diamond, Cecile Rose T. Vibat, Latifa Hassaine, Jason C. Poole, Minal Patel, Veronica R. Holley, Goran Cabrilo, Timothy T. Lu, Maria E. Arcila, Young Rock Chung, Raajit Rampal, Mario E. Lacouture, Neal Rosen, Funda Meric-Bernstam, José Baselga, Razelle Kurzrock, Mark G. Erlander, Filip Janku, Omar Abdel-Wahab
Journal: Cancer Discovery (2014)

Patients with Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) have a high frequency of BRAF(V600E) mutations and respond to RAF inhibitors. However, detection of mutations in tissue biopsies is particularly challenging in histiocytoses due to low tumor content and stromal contamination. We applied a droplet-digital PCR assay for quantitative detection of the BRAF(V600E) mutation in plasma and urine cell-free (cf) DNA and performed a prospective, blinded study in 30 patients with ECD/LCH. There was 100% concordance between tissue and urinary cfDNA genotype in treatment-naïve samples. cfDNA analysis facilitated identification of previously undescribed KRAS(G12S)-mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies. These results indicate that cfDNA BRAF(V600E) mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a noninvasive biomarker to monitor response to therapy in LCH and ECD.Patients with BRAF(V600E)-mutant histiocytic disorders have remarkable responses to RAF inhibition, but mutation detection in tissue in these disorders is challenging. Here, we identify that analysis of plasma and urinary cfDNA provides a reliable method to detect the BRAF(V600E) mutation and monitor response to therapy in these disorders.
Diagnostic value of 9 am plasma adrenocorticotrophic hormone concentrations in Cushing's disease.
Authors: P M Horrocks, D R London
Journal: BMJ (1982)

Morning plasma adrenocorticotrophic hormone (ACTH) concentrations were measured in 58 normal subjects and seven patients with pituitary-dependent Cushing's syndrome (Cushing's disease). Particular note was taken of the time of venepuncture. The range of values for the normal subjects irrespective of timing was 9-77 ng/l. The range between 9 0 am and 9 30 am was 9-24 ng/l. In the patients with Cushing's disease the ACTH concentrations were in the range 39-109 ng/l. To distinguish patients with Cushing's disease from normal subjects it is therefore important to define accurately the 9 am normal range, since these results show no overlap.
Undiagnosed hepatitis C virus infection in hemodialysis patients: Value of HCV RNA and liver enzyme levels
Authors: Carlos Caramelo, Javier Bartolomé, Marta Albalate, Patricia de Sequera, Sonia Navas, Teresa Bermejillo, Horacio Oliva, Eduardo Marriott, Alberto Ortiz, Carmen Ruiz Tuñón, Santos Casado, Vicente Carreño
Journal: Kidney International (1996)
INTOXICATION AND INSANITY.
Authors: J. T. SEARCY
Journal: JAMA (1896)

I will be glad to limit the meaning of the word intoxication, in this paper, to the injurious effects on the cerebrum of toxic agents present in the circulation. Toxic agents in the blood, of course, have their chemic effects upon other structures, but in the ordinary interpretation of the word, the symptoms of intoxication are those that belong to the brain. I will use the word in that sense. This organ is exceedingly sensitive to the action of certain agents; so much so, in certain instances, that it seems to be the only organ affected, or affected so far in advance of others that their disturbance is not appreciated. The exceedingly soft colloid character of the functionating central parts of its nerve cells and fibers render them the most sensitive of all the structures of the body to some agents; and their excessively rapid functional motion is most delicately
On the Physical Death of Jesus Christ
Authors: Norman A. Marcus
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The most recent post mortem on Jesus of Nazareth<sup>1</sup>brings new meaning to the pseudoscience of forensic mythology. The reader must ask, is the author's avowed purpose of presenting an "accurate account of the physical death of the one called Jesus Christ" naive enough to be true, or are we witnessing yet another revisionist approach to history? It would certainly not be the first time that assumptions, hearsay, prejudice, and gossip have been given the legitimacy of "fact" by being discussed in a "scientific" context. The Jewish people are held accountable for the death of Jesus no less than six times, with care to ensure that the Romans are given equal time and, in fact, special credit for administering the coup de grace. The juxtaposition of such assertions with anatomically accurate pictures of barbarism and torture (is that too a modern medical interpretation?) is thinly veiled anti-Semitism
Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis
Authors: Rikhia Chakraborty, Oliver A. Hampton, Xiaoyun Shen, Stephen J. Simko, Albert Shih, Harshal Abhyankar, Karen Phaik Har Lim, Kyle R. Covington, Lisa Trevino, Ninad Dewal, Donna M. Muzny, Harshavardhan Doddapaneni, Jianhong Hu, Linghua Wang, Philip J. Lupo, M. John Hicks, Diana L. Bonilla, Karen C. Dwyer, Marie-Luise Berres, Poulikos I. Poulikakos, Miriam Merad, Kenneth L. McClain, David A. Wheeler, Carl E. Allen, D. Williams Parsons
Journal: Blood (2014)
Electrodiagnosis and Electromyography
Authors: G. Osborne
Journal: BMJ (1962)

<b>Objective:</b> To investigate the relation between income inequality and life expectancy in Italy and across wealthy nations. <b>Design and setting:</b> Measure correlation between income inequality and life expectancy at birth within Italy and across the top 21 wealthy countries. Pearson correlation coefficients were calculated to study these relations. Multivariate linear regression was used to measure the association between income inequality and life expectancy at birth adjusting for per capita income, education, and/or per capita gross domestic product. <b>Data sources:</b> Data on the Gini coefficient (income inequality), life expectancy at birth, per capita income, and educational attainment for Italy came from the surveys on Italian household on income and wealth 1995–2000 and the National Institute of Statistics information system. Data for industrialised nations were taken from the United Nations Development Program’s human development indicators database 2003. <b>Results:</b> In Italy, income inequality (β = −0.433; p&lt;0.001) and educational attainment (β = 0.306; p&lt;0.001) were independently associated with life expectancy, but per capita income was not (β = 0.121; p&gt;0.05). In cross national analyses, income inequality had a strong negative correlation with life expectancy at birth (<i>r</i> = −0.864; p&lt;0.001). <b>Conclusions:</b> In Italy, a country where health care and education are universally available, and with a strong social safety net, income inequality had an independent and more powerful effect on life expectancy at birth than did per capita income and educational attainment. Italy had a moderately high degree of income inequality and an average life expectancy compared with other wealthy countries. The cross national analyses showed that the relation between income inequality and population health has not disappeared.
A man with Wegener's granulomatosis and haemoptysis
Authors: R. Lee, R. Martin, D. D'Cruz
Journal: BMJ (2009)

A 60 year old man with Wegener’s granulomatosis who was clinically stable on methotrexate presented with a two day history of haemoptysis. On examination he was febrile, with bibasal crepitations and bronchial breath sounds in the left upper zone. Pulse oximetry showed an oxygen saturation of 96% on air. A full blood count showed that his haemoglobin was 134 g/l, white blood cells were 18.4×109/l (neutrophils 15.3×109/l), and serum creatinine was 74 μmol/l. He had a titre of 1:160 on recent serological testing for cytoplasmic staining antineutrophil cytoplasmic antibodies. Urinalysis detected trace amounts of protein and blood, but he had no dysmorphic red cells or casts on urine microscopy. He underwent computed tomography of the chest and chest radiography (figs 1⇓ and 2⇓). Fig 1 Chest radiograph Fig 2 Computed tomography of the chest ### Short answers Fig 3 Chest radiograph showing bibasal and right upper lobe air space shadowing Fig 4 Computed tomography of the chest confirming bilateral air space infiltrates (arrowheads) and surrounding ground glass shadowing
Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®)
Authors: Thierry Poynard, Julien Vergniol, Yen Ngo, Juliette Foucher, Mona Munteanu, Wassil Merrouche, Massimo Colombo, Vincent Thibault, Eugene Schiff, Clifford A. Brass, Janice K. Albrecht, Marika Rudler, Olivier Deckmyn, Pascal Lebray, Dominique Thabut, Vlad Ratziu, Victor de Ledinghen
Journal: Journal of Hepatology (2013)
Meningococcal infections during infancy: confidential inquiries into 10 deaths.
Authors: J R Oakley, A N Stanton
Journal: BMJ (1979)

The first 10 deaths from meningococcal infections in children aged under 2 years that were reported to a DHSS multicentre study were reviewed. Confidential inquiries were made of the parents, family doctors, health visitors, and hospital staff concerned with each case, and management was discussed with a paediatrician and pathologist. Diagnosis and treatment were often delayed because doctors did not realise the importance of the purpuric rash. One child died at home, and by the time they were admitted to hospital all the remaining nine were shocked and needed resuscitation. Prodromal symptoms, mainly changes in behaviour, preceded the rash in all cases. These prodromal symptoms should arouse the suspicion of septicaemia and prompt a search for petechiae so that early effective treatment may be started.
Abstract P2-09-18: Identification of synergistic drug combination for HER2 positive breast cancer
Authors: P Chalugun, JS Shim, JO Liu
Journal: Cancer Research (2013)

Abstract Breast cancer is one of the leading causes of death worldwide. 25-30% of breast cancer has HER2 gene amplification, which tend to give rise to poorly-differentiated and high grade tumor with a higher likelihood of spreading. Currently, trastuzumab and lapatinib are the only two FDA-approved treatments that target HER2 positive breast cancer. However, resistance to both drugs is already reported. Since breast cancer is considered to be one of genetic diseases caused by multiple gene aberrations, we used synergistic drug combination as a strategy to overcome these growth signaling pathway abnormalities. To identify new drug combination with lapatinib, we performed a cell-based screen against a library of clinical drugs of 3,200 compounds. Triptolide, a traditional Chinese medicine emerged from the screen with strong synergistic effect with lapatinib in HER2 positive breast cancer cells. This effect was specific to HER2 positive breast cancer. The whole HER2 signaling pathway was inhibited and more cells underwent apoptosis. Besides, both HER2 protein and mRNA levels were decreased in cells treated with the combination. This drug combination was also effective in breast cancer xenograft models of mice. Together, these findings suggest that both triptolide and lapatinib can be used as a promising drug combination for HER2 positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-18.
Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).
Authors: Rosette L Van Den Heuvel, Gudrun Koppen, Jan A Staessen, Elly Den Hond, Geert Verheyen, Tim S Nawrot, Harry A Roels, Robert Vlietinck, Greet E R Schoeters
Journal: Environmental Health Perspectives (2002)

In this study, we investigated 17- to 18-year-old boys and girls to determine whether changes in humoral or cellular immunity or respiratory complaints were related to blood serum levels of polychlorinated biphenyls (PCBs) and dioxin-like compounds after lifetime exposure in Flanders (Belgium). We obtained blood samples from and administered questionnaires to 200 adolescents recruited from a rural area and two urban suburbs. Physicians recorded medical history and respiratory diseases. We measured immunologic biomarkers such as differential blood cell counts, lymphocyte phenotypes, and serum immunoglobulins. As biomarkers of exposure, we determined the serum concentrations of PCBs (PCB 138, PCB 153, and PCB 180) and dioxin-like compounds [chemical-activated luciferase expression (CALUX) bioassay]. The percentages of eosinophils and natural killer cells in blood were negatively correlated with CALUX toxic equivalents (TEQs) in serum (p = 0.009 and p = 0.05, respectively). Increased serum CALUX TEQs resulted in an increase in serum IgA levels (p = 0.05). Furthermore, levels of specific IgEs (measured by radioallergosorbent tests) of cat dander, house dust mite, and grass pollen were also significantly and negatively associated with the CALUX TEQ, with odds ratios (ORs) equal to 0.63 [95% confidence interval (CI), 0.42-0.96], 0.68 (0.5-0.93), and 0.70 (0.52-0.95), respectively. In addition, reported allergies of the upper airways and past use of antiallergic drugs were negatively associated with CALUX TEQs, with ORs equal to 0.66 (0.47-0.93) and 0.58 (0.39-0.85), respectively. We found a negative association between IgGs and marker PCBs in serum (p = 0.009). This study shows that immunologic measurements and respiratory complaints in adolescents were associated with environmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs). The negative correlation between PHAHs and allergic responses in adolescents suggested that exposure may entail alterations in the immune status.
Private health sector in India
Authors: Amitava Bose
Journal: BMJ (2005)

Editor—Sengupta and Nundy's editorial makes good reading, but I do not see any connection between the burgeoning private healthcare sector in India and the abysmal condition of the government healthcare system.1

To say that private healthcare is growing at the cost of public health care is unfair. While public spending on health care has been dropping, during the first half of the 1990s, India's defence budget grew at 1.5% yearly in real terms. Since 1996-7, the defence budget has been growing at 10% yearly in real terms.2 Would it not be appropriate to say that defence spending is growing at the cost of public health care?

Patients from other countries and patients from eastern India go to south India for treatment at private institutions since these are perceived to offer better treatment than their counterparts in eastern India. The levying of a tax on hospital bills of foreign patients, to be credited to a “fund for the poor,” or diverting a portion of the revenue earned from medical tourism to the government to be spent on health care would not work. Patients from eastern India should then contribute to the coffers of the state governments in south India. Also, in all probability this revenue will end being spent on defence.

Private health care in India is expensive for Indian patients: 28-30% of the project cost of a 100 bed hospital and upwards relates to recurrent expenditure on medical equipment. Maintenance costs and import duties for such equipment are high. The saying in private hospitals is: “Spend in US dollars and earn in Indian rupees.”

Private health care is there for those who can afford it. Berating private health care for not assuming the government's role in providing health care to its citizens is not the solution.
The association of genetic variants of type 2 diabetes with kidney function
Authors: Nora Franceschini, Nawar M. Shara, Hong Wang, V Saroja Voruganti, Sandy Laston, Karin Haack, Elisa T. Lee, Lyle G. Best, Jean W. MacCluer, Barbara J. Cochran, Thomas D. Dyer, Barbara V. Howard, Shelley A. Cole, Kari E. North, Jason G. Umans
Journal: Kidney International (2012)
Prevalence and Outcomes of Cataract Surgery in Rural China
Authors: Jialiang Zhao, Leon B. Ellwein, Hao Cui, Jian Ge, Huaijin Guan, Jianhua Lv, Xianzhi Ma, Jinglin Yin, Zheng Qin Yin, Yuansheng Yuan, Hu Liu
Journal: Ophthalmology (2010)
Immunologic potential of donor lymphocytes expressing a suicide gene for early immune reconstitution after hematopoietic T-cell–depleted stem cell transplantation
Authors: Sarah Marktel, Zulma Magnani, Fabio Ciceri, Sabrina Cazzaniga, Stanley R. Riddell, Catia Traversari, Claudio Bordignon, Chiara Bonini
Journal: Blood (2003)
Efficacy and Safety of Pemetrexed Maintenance Therapy versus Best Supportive Care in Patients from East Asia with Advanced, Nonsquamous Non-small Cell Lung Cancer: An Exploratory Subgroup Analysis of a Global, Randomized, Phase 3 Clinical Trial
Authors: Chandra Prakash Belani, Yi-Long Wu, Yuh-Min Chen, Joo-Hang Kim, Sung-Hyun Yang, Li Zhang, Patrick Peterson, Mauro Orlando
Journal: Journal of Thoracic Oncology (2011)
Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia
Authors: Zachary A. Hing, Rose Mantel, Kyle A. Beckwith, Daphne Guinn, Erich Williams, Lisa L. Smith, Katie Williams, Amy J. Johnson, Amy M. Lehman, John C. Byrd, Jennifer A. Woyach, Rosa Lapalombella
Journal: Blood (2015)
DEATH FROM BRONCHIAL ASTHMA
Authors: C. B. WRIGHT
Journal: JAMA (1930)

Death due to a paroxysm of bronchial asthma is very rare. Huber and Koessler,<sup>1</sup>in 1922, could find only twenty-one cases of death due to asthma reported in the literature. Rackemann later reviewed the twenty-one cases reported by Huber and Koessler and added one other case. He concluded that in no more than eleven cases of those reported had death resulted from the immediate effects of asthma. Kountz and Alexander,<sup>2</sup>in 1928, found in the literature about thirty cases in which autopsies with microscopic studies had been made. Several of the cases, they decided, were not true bronchial asthma, and in other cases death took place from intercurrent disease. They also reported three additional cases with detailed postmortem analyses. Death in each of these three cases was directly attributed to the effects of asthma. The case reported here was carefully observed clinically from onset to termination, with postmortem
When It Comes to Electric Vehicle Emissions, Location Matters
Authors: David C. Holzman
Journal: Environmental Health Perspectives (2012)

When the U.S. FDA announced new rules for sunscreen labeling in June 2011, manufacturers were given a year to comply. 1 In May 2012 the agency announced a six-month delay in enforcement to give manufacturers extra time to retool labels and complete broad-spectrum testing for their products. 2Under the new regulations, sunscreen products including cosmetics and moisturizers must back up labeling claims with testing to ensure they deliver the promised amount of protection.Only products with an SPF higher than 15 can claim they reduce risks of skin cancer and early aging, and labels may no longer use the vague and unsubstantiated terms "waterproof" and "sweatproof," but instead must state how long products offer water-resistant protection.
When I use a word...: Hippopotamonstrosesquipedalian
Authors: J. Aronson
Journal: BMJ (1997)

What is the longest English word? Not a difficult question to answer, you might think, but the winner is not so easy to decide. The first problem is to define what one means by a word. For example, Mrs Byrne in her Dictionary of Unusual, Obscure and Preposterous Words (no, I'm not making it up) mentions a polypeptide enzyme whose name contains 1913 letters, consisting of the string of terms used to describe each of its 267 constituent amino acids; it starts methionyl-glutaminylarginyl- and ends …
Lung thallium-201 uptake after stress testing in patients with coronary artery disease.
Authors: F G Kushner, R D Okada, H D Kirshenbaum, C A Boucher, H W Strauss, G M Pohost
Journal: Circulation (1981)

We observed increased lung thallium-201 (201T1) activity on initial stress myocardial images in patients with coronary artery disease (CAD).To assess the clinical significance of this finding, initial and 2- hour delayed 201T1 images were stored in a computer immediately after supine stress testing in 49 patients (39 with CAD and 10 controls).Regions of interest over the heart and lung were selected on the computer-gen- erated images and quantitative lung 201T1 activity was expressed as a percentage of maximal myocardial 201T1 activity per picture element (lung 201T1 index) for each imaging time.The lung 201T1 index was then compared with (1) the extent of CAD at catheterization, (2) resting left ventricular ejection fraction by multigated blood pool scintigraphy, (3) the results of the initial 201T1 stress myocardial perfusion images, and (4) qualitative assessment of initial lung 201T1 uptake after stress.In 10 control patients the mean initial lung 20MT1 index was 37.6 + 2.5% (± SEM).In 29 patients with two-and three-vessel CAD, the mean initial lung 201T1 index was elevated, at 53.5 ± 2.2% (p < 0.001 compared with controls), while in 10 patients with one-vessel CAD, the mean initial lung 201T1 index was 45.6 ± 3.6% (p = NS compared with controls).Patients with CAD decreased their mean lung 201T1 index from initial to delayed images (p < 0.05), but control patients did not.When a lung 201T1 index of 54.5% (2 SD above the control mean) was chosen as abnormal, patients who had CAD and an ab- normal initial lung 201T1 index had significantly reduced resting ejection fractions (mean 58.2 ± 2.5%) com- pared with patients who had CAD and a normal lung 201T1 index (mean 66.0 + 2.1%) (p < 0.05).Patients with CAD and four or five of six abnormal segments on the initial myocardial perfusion images had higher initial lung 201T1 indexes (mean 59.1 + 13.0%) compared with patients with CAD and one or no abnormal segments on the initial myocardial perfusion images (mean 44.5 ± 10.3%) (p < 0.01).Initial lung `01TI indexes de- termined quantitatively correlated with the qualitative assessment of initial lung 201T1 uptake after stress.The finding of elevated lung 201T1 activity on stress myocardial images correlates with increased severity of underlying coronary artery disease and left ventricular dysfunction.201T1 lung activity after stress can be easily quantitated.