tbuckley/cabot-search huggingface dataset:
The view from space
Authors: T. Delamothe
Journal: BMJ (2012)

What would extraterrestrials make of life on earth if all they had to go on was this year’s Christmas BMJ ? Such an event is not so unlikely. A corrupted line of computer code could easily beam the issue’s contents out to Alpha Centauri rather than on to readers’ iPads.

Given that so many articles focus on times past, extraterrestrials’ overwhelming impression might be that earthlings are happier looking backwards than forwards. The past may be another country, but that’s apparently where they prefer to live.

Setting the scene is the first editorial, which hymns a prelapsarian past before NHS managers seized the whip hand from doctors (doi:10.1136/bmj.e8239). Less fraught nostalgia is on offer in articles on the short lived genre …
The Frequency Distribution of Nucleotide Variation in Drosophila simulans
Authors: David J. Begun
Journal: Molecular Biology and Evolution (2001)

Patterns of codon bias in Drosophila suggest that silent mutations can be classified into two types: unpreferred (slightly deleterious) and preferred (slightly beneficial). Results of previous analyses of polymorphism and divergence in Drosophila simulans were interpreted as supporting a mutation-selection-drift model in which slightly deleterious, silent mutants make significantly greater contributions to polymorphism than to divergence. Frequencies of unpreferred polymorphisms were inferred to be lower than frequencies of other silent polymorphisms. Here, I analyzed additional D. simulans data to reevaluate the support for these ideas. I found that D. simulans has fixed more unpreferred than preferred mutations, suggesting that this lineage has not been at mutation-selection-drift equilibrium at silent sites. Frequencies of polarized unpreferred polymorphisms are not skewed toward rare alleles. However, frequencies of unpolarized unpreferred codons are lower in high-bias genes than in low-bias genes. This supports the idea that unpreferred codons are borderline deleterious mutations. Purifying selection on silent sites appears to be stronger at twofold-degenerate codons than at fourfold-degenerate codons. Finally, I found that X-linked polymorphisms occur at a higher average frequency than polymorphisms on chromosome arm 3R, even though an average X-linked site is significantly less likely to be polymorphic than an average site on 3R. This result supports a previous analysis of D. simulans indicating different population genetics of X-linked versus autosomal mutations.
Abstract 4205: Simultaneous high resolution fluorescence imaging of cellular DNA and RNA enabled by complex oligonucleotide libraries in various sample types.
Authors: Robert A. Ach, Peter Tsang, Alicia Scheffer-Wong, Laurakay Bruhn, Weston Powell, Janine LaSalle, Alice Yamada
Journal: Cancer Research (2013)

Abstract Fluorescence in situ Hybridization (FISH) is a powerful technique for determining the structure, organization, and localization of specific nucleic acid sequences within individual cells. However, the use of FISH has often been dependent upon access to cloned template DNA for the generation of probes, which can be difficult if clones for specific regions are unavailable, or if the genomic region of interest contains repetitive and/or other problematic sequences. We have leveraged our ability to chemically synthesize DNA in massively parallel reactions to produce libraries of oligonucleotides up to 200 bases in length that can be used for the generation of FISH probes. The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to avoid repetitive elements or regions homologous to other non-targeted loci. Using oligonucleotide library-derived FISH probes on DNA, human genomic regions as small as 1.8 kb and as large as whole chromosomes can be visualized in both metaphase and interphase cells using the same simple assay protocol. Because of the inherent flexibility in our probe design methods, we readily visualized regions rich in repeats and/or GC content. We have also used these oligonucleotide library-derived FISH probes to detect the localization of a variety of both coding and non-coding RNAs in fixed cells, using both conventional fluorescence and structured illumination microscopy. Simultaneous hybridization of FISH probes labeled with different fluorophores enables visualization of multiple sequences at once. Using probes designed specifically to transcribed vs. non-transcribed regions, we have been able to simultaneously detect DNA and RNA from the same locus in the same FISH assay. We have successfully used this technique in several types of fixed tissue culture cells as well as in formalin-fixed paraffin-embedded tissue sections. Our oligo FISH methods are readily compatible with the co-detection of cellular proteins by immunocytochemistry. The ability to generate high performance FISH probes using chemically synthesized oligo libraries that can work flexibly with co-detection of other molecules yields a valuable tool for studies of how localization of specific nucleic acids impacts biological function. Citation Format: Robert A. Ach, Peter Tsang, Alicia Scheffer-Wong, Laurakay Bruhn, Weston Powell, Janine LaSalle, Alice Yamada. Simultaneous high resolution fluorescence imaging of cellular DNA and RNA enabled by complex oligonucleotide libraries in various sample types. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4205. doi:10.1158/1538-7445.AM2013-4205
Survey highlights health risks of overseas travel
Authors: R. Dobson
Journal: BMJ (2004)

All large hospitals in the United Kingdom should have clinical staff specialising in infectious diseases to cope with the rise in overseas travel and the emergence of new diseases, says a new report.

Researchers who carried out an audit at Addenbrooke's Hospital, Cambridge, of cases of imported infections also call for more education about the prevention of malaria.

Malaria accounted for the largest number of cases in the survey—85 out of a total of 301—and the …
Novel Noninvasive Breath Test Method for Screening Individuals at Risk for Diabetes
Authors: E. Lichar Dillon, Morteza Janghorbani, James A. Angel, Shanon L. Casperson, James J. Grady, Randall J. Urban, Elena Volpi, Melinda Sheffield-Moore
Journal: Diabetes Care (2008)

Diagnosis of pre-diabetes and early-stage diabetes occurs primarily by means of an oral glucose tolerance test (OGTT), which requires invasive blood sampling. The aim of this study was to determine whether differences exist in breath (13)CO(2) excretion during a (13)C-labeled OGTT between individuals with normal glucose tolerance (NGT) and individuals with pre-diabetes and early-stage diabetes (PDED) and whether these differences correlated with blood glucose kinetics.Blood and breath samples were collected at baseline and every 30 min for a 10-h period after ingestion of 75 g glucose isotopically labeled with 150 mg [U-(13)C(6)]D-glucose.Age (56 +/- 5 vs. 47 +/- 3 years) and BMI (31 +/- 2 vs. 31 +/- 2 kg/m(2)) were not different between individuals with NGT (n = 10) and PDED (n = 7), respectively. Blood glucose concentrations were significantly higher in those with PDED compared with those with NGT from baseline to 4.5 h after glucose ingestion (P <or= 0.05). Glucose-derived breath (13)CO(2) was significantly lower in individuals with PDED compared with those with NGT from 1 to 3.5 h after glucose (P <or= 0.05). Peak breath (13)CO(2) abundance occurred at 4.5 and 3.5 h in individuals with PDED and NGT, respectively (36.87 +/- 3.15 vs. 41.36 +/- 1.56 per thousand delta over baseline).These results suggest that this novel breath test method may assist in recognition of pre-diabetes or early-stage diabetes in at-risk persons without the need for invasive blood sampling, thus making it an attractive option for large-scale testing of at-risk populations, such as children.
Handedness among surgeons
Authors: J. Schott, M. Puttick
Journal: BMJ (1995)

Radiologists, who every year scan hundreds of livers of all shapes, positions, and sizes, are better placed than anyone else to comment on the inappropriateness of performing blind right intercostal punctures with large calibre needles.They are also, by training and experience, the most expert in placing biopsy needles of all kinds under imaging guidance and are probably just waiting to be asked.
Abstract LB-215: The TAM family of receptor tyrosine kinases play a role in acquired resistance to cetuximab
Authors: Toni Michel Brand, Mari Iida, Kelsey L. Corrigan, Neha Luthar, Megan Hornung, Mahmoud Toulany, Parkash Gill, Ravi Salgia, Deric L. Wheeler
Journal: Cancer Research (2014)

Abstract Cetuximab is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has shown efficacy in metastatic colorectal cancer, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC). Clinical data suggests that patients whom initially respond to cetuximab eventually acquire resistance, highlighting the importance of understanding resistant mechanisms for the development of better treatment regimes for cancer patients. Recent studies have identified a role for the TAM family of receptor tyrosine kinases (Tyro, Axl, and Mer) in tumor biology, and more specifically the Axl receptor as playing a key role in promoting tumor growth and metastasis. In the current study, we utilized NSCLC and HNSCC models of acquired resistance to cetuximab and found that Axl was overexpressed, activated, and highly associated with EGFR as compared parental controls. Further, using siRNA technology and novel Axl targeting agents (antibody and tyrosine kinase inhibitor), Axl was found to regulate proliferation, EGFR activation, and MAPK signaling in cetuximab resistant clones (CtxR). Additionally, Axl mRNA expression was regulated by EGFR induced MAPK activation in resistant cells. To investigate the role of Axl in in vivo models of acquired resistance to cetuximab, de novo acquired resistance was created by prolonged treatment of cetuximab sensitive (CtxS) tumor xenografts with cetuximab. Analysis of resultant CtxR tumors demonstrated that Axl was hyperactivated and highly associated with EGFR as compared to vehicle treated tumors. In addition, CtxR tumors expressing the highest levels of phosphorylated Axl also expressed hyperactivated EGFR, supporting the role of Axl in EGFR activation. Finally, to expand these findings to other members of the TAM family, Tyro, Axl, or Mer were stably overexpressed in CtxS parental NSCLC cells and tested for cetuximab response. The results of this experimentation indicated that stable overexpression of each TAM receptor rendered CtxS cells resistant to cetuximab therapy. Collectively, the studies presented herein identify the TAM family of receptors as key players in acquired resistance to cetuximab and provide rationale for the clinical evaluation of anti-TAM receptor therapeutics in the resistant setting. Citation Format: Toni Michel Brand, Mari Iida, Kelsey L. Corrigan, Neha Luthar, Megan Hornung, Mahmoud Toulany, Parkash Gill, Ravi Salgia, Deric L. Wheeler. The TAM family of receptor tyrosine kinases play a role in acquired resistance to cetuximab. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-215. doi:10.1158/1538-7445.AM2014-LB-215
Senior doctors criticise government report on allergy treatment
Authors: Paul Dinsdale
Journal: BMJ (2006)

Doctors' leaders have criticised a report on the treatment of allergies by the Department of Health in England for not proposing strong enough action to improve services.

The report places the onus on family doctors, who, it says, need to be better trained in the detection and treatment of allergies, and it proposes that they work with the medical royal colleges to this end.

The Department of Health's report follows a year long review, which was prompted by calls from the parliamentary health select committee in 2004 for better services for allergy.

Around a third of the population …
130-nm Albumin–Bound Paclitaxel Enhances Tumor Radiocurability and Therapeutic Gain
Authors: Nicole Wiedenmann, David Valdecanas, Nancy Hunter, Stephen Hyde, Thomas A. Buchholz, Luka Milas, Kathryn A. Mason
Journal: Clinical Cancer Research (2007)

Abstract Purpose: 130-nm albumin–bound paclitaxel (nab-paclitaxel) is a novel solvent-free albumin-bound paclitaxel, designed to avoid solvent-related toxicity. Nab-paclitaxel has been successfully introduced into the clinic but its radiation-enhancing potential has not yet been evaluated. We conducted a preclinical evaluation of the radiation-modulating effects of nab-paclitaxel in tumor and normal tissues. Experimental Design: Mice bearing syngeneic ovarian or mammary carcinomas were treated with nab-paclitaxel, radiation, or combination of both. Nab-paclitaxel was administered at 90 mg/kg, 1.5 times the maximum tolerated dose for solvent-based paclitaxel. End points were antitumor efficacy (growth delay, radiocurability, and cellular effects) and normal tissue toxicity (gut and skin). Results: Nab-paclitaxel showed single-agent antitumor efficacy against both tumor types and acted as a radiosensitizer. Combined with radiation, nab-paclitaxel produced supra-additive effects when given before radiation. Nab-paclitaxel significantly increased radiocurability by reducing the dose yielding 50% tumor cure (TCD50) from 54.3 to 35.2 Gy. Tumor histology following nab-paclitaxel treatment was characterized by pronounced necrotic and apoptotic cell death and mitotic arrest. Nab-paclitaxel did not increase normal tissue radioresponse. Conclusions: Nab-paclitaxel exhibited strong antitumor efficacy against both tumors as a single agent and it improved radiotherapy in a supra-additive manner. These improved effects were achieved without increased normal tissue toxicity to either rapidly or slowly proliferating normal tissues although the drug dose was 1.5 times higher than the maximum tolerated dose of solvent-based paclitaxel. These preclinical findings show that combining nab-paclitaxel with radiotherapy would improve the outcome of taxane-based chemoradiotherapy. This novel taxane is thus a good candidate for testing in clinical chemoradiotherapy trials.
The Appendicitis Question.
Authors: J. H. Carstens
Journal: JAMA (1898)

Detroit, Mich., Feb. 14, 1898. <h3>To the Editor:</h3> —It has been a rule in my life never to go into a controversy with people, although I have sometimes sent communications to theJournal, giving my views when I disagreed with others. My friend from Richmond, Ind., has sent a long reply to my last communication, and, after carefully reading it, I have come to the conclusion that he is a nice, good fellow and a progressive physician at heart, and if we bring our views together I am sure we will perfectly agree, excepting on some minor details. He quotes Treves and Thalamon, both of whom had limited experience with the operation of appendicitis, and whose opinions should not count alongside of such men as Robert Morris, J. B. Murphy, Joseph Price, Fowler and Deaver, men who have had hundreds of operations and seen the terrible results of procrastination. When
Lingual Infarction in Cranial Arteritis
Authors: Robert A. Sofferman
Journal: JAMA (1980)

Cranial arteritis is commonly found in elderly individuals with headache and visual loss. Although otolaryngologic manifestations of cranial arteritis are said to be infrequent, approximately 25% of patients may have complaints or objective findings limited to the oral cavity. Masticatory claudication, tongue pain, and frank lingual infarction are the most common and should be recognized as indicators of a serious underlying arteritis. These symptoms are often confusing to internists, neurologists, and otolaryngologists, resulting in delays in diagnosis and initiation of proper therapy.
Geographical patterns of the standing and active human gut microbiome in health and IBD
Authors: Ateequr Rehman, Philipp Rausch, Jun Wang, Jurgita Skieceviciene, Gediminas Kiudelis, Ketan Bhagalia, Deepak Amarapurkar, Limas Kupcinskas, Stefan Schreiber, Philip Rosenstiel, John F Baines, Stephan Ott
Journal: Gut (2015)

<h3>Objective</h3> A global increase of IBD has been reported, especially in countries that previously had low incidence rates. Also, the knowledge of the human gut microbiome is steadily increasing, however, limited information regarding its variation on a global scale is available. In the light of the microbial involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated mucosal microbiota patterns from different geographical regions including Europe (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling based on 16S rRNA transcripts provides additional resolution, both of which may hold important clinical relevance. <h3>Design</h3> In this study, we analyse a set of 89 mucosal biopsies sampled from individuals of German, Lithuanian and Indian origins, using bacterial community profiling of a roughly equal number of healthy controls, patients with Crohn9s disease and UC from each location, and analyse 16S rDNA and rRNA as proxies for standing and active microbial community structure, respectively. <h3>Results</h3> We find pronounced population-specific as well as general disease patterns in the major phyla and patterns of diversity, which differ between the standing and active communities. The geographical origin of samples dominates the patterns of β diversity with locally restricted disease clusters and more pronounced effects in the active microbial communities. However, two genera belonging to the <i>Clostridium leptum</i> subgroup, <i>Faecalibacteria</i> and <i>Papillibacter</i>, display consistent patterns with respect to disease status and may thus serve as reliable 'microbiomarkers'. <h3>Conclusions</h3> These analyses reveal important interactions of patients' geographical origin and disease in the interpretation of disease-associated changes in microbial communities and highlight the added value of analysing communities on both the 16S rRNA gene (DNA) and transcript (RNA) level.
Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. Studies in lean and obese men.
Authors: A D Baron, G Brechtel, A Johnson, N Fineberg, D P Henry, H O Steinberg
Journal: Journal of Clinical Investigation (1994)

To explore the interactions between insulin action and norepinephrine (NE) on blood pressure and muscle vascular resistance, we studied seven lean (66 +/- 1 kg) sensitive and seven age-matched obese (96 +/- 3 kg) insulin-resistant men after an overnight fast. Both groups were normotensive; however, the obese exhibited higher basal blood pressure, 90.8 +/- 2.2 vs. 83.4 +/- 1.6 mmHg, P < 0.04. Each subject was studied on two separate days during either saline (S) infusion or a euglycemic hyperinsulinemic clamp (I) achieving insulin concentrations of approximately 70 microU/ml. After 180 min of either S or I, NE was infused systemically at rates of approximately 50, 75, and 100 pg/kg per min. Glucose uptake was measured in whole body ([3-3H]glucose) and in leg by the balance technique. The results indicate: (a) the NE/pressor dose-response curve was decreased (shifted to the right) during I in lean but not in obese subjects, (b) I enhanced NE metabolic clearance by 20% in lean but not in obese, (c) NE decreases leg vascular resistance more in lean than in obese, and (d) NE causes a approximately 20% increase in insulin-mediated glucose uptake in both groups. In conclusion, insulin resistance of obesity is associated with an apparent augmented NE pressor sensitivity and decreased NE metabolic clearance. Both of these mechanisms can potentially contribute to the higher incidence of hypertension in obese man. Insulin resistance is likely to be a predisposing but not sufficient factor in the pathogenesis of hypertension. Because the obese group exhibited higher basal blood pressure, it is possible that our results reflect this difference. Further studies will be required to clarify this issue.
Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.
Authors: F Pott, M Roller, K Kamino, B Bellmann
Journal: Environmental Health Perspectives (1994)

At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS)
A SIMPLE METHOD OF EXTUBATION
Authors: John Leshure
Journal: JAMA (1924)

Most intubationists will agree that the extraction of an intubation tube is often more difficult than its introduction, especially in infants and young children whose throats are small. The short arm of the curved extraction forceps is usually so long that difficulty is experienced with these young patients in elevating the handle sufficiently to grasp the tube. Moreover, the forceps are liable to injure the tissues more or less, especially in the retained tube cases, in which granulations are often present. In the method that I employ, the child is swathed and gagged as usual without being removed from the bed, the pillow is removed, and a folded towel is placed under the neck to increase extension. The operator's left index finger is applied to the episternal notch, and pressure is made dorsally and upward, causing the tube to rise, when it can be grasped by the index and middle
Paradoxical secondary polycythemia in von Hippel-Lindau patients treated with anti–vascular endothelial growth factor receptor therapy
Authors: Stéphane Richard, Laure Croisille, Jeannine Yvart, Nicole Casadeval, Pascal Eschwège, Nozar Aghakhani, Philippe David, Alain Gaudric, Paul Scigalla, Olivier Hermine
Journal: Blood (2002)