tbuckley/cabot-search huggingface dataset:
Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent Patient Cohorts
Authors: D. Neil Hayes, Stefano Monti, Giovanni Parmigiani, C. Blake Gilks, Katsuhiko Naoki, Arindam Bhattacharjee, Mark A. Socinski, Charles Perou, Matthew Meyerson
Journal: Journal of Clinical Oncology (2006)

Published reports suggest that DNA microarrays identify clinically meaningful subtypes of lung adenocarcinomas not recognizable by other routine tests. This report is an investigation of the reproducibility of the reported tumor subtypes.Three independent cohorts of patients with lung cancer were evaluated using a variety of DNA microarray assays. Using the integrative correlations method, a subset of genes was selected, the reliability of which was acceptable across the different DNA microarray platforms. Tumor subtypes were selected using consensus clustering and genes distinguishing subtypes were identified using the weighted difference statistic. Gene lists were compared across cohorts using centroids and gene set enrichment analysis.Cohorts of 31, 72, and 128 adenocarcinomas were generated for a total of 231 microarrays, each with 2,553 reliable genes. Three adenocarcinoma subtypes were identified in each cohort. These were named bronchioid, squamoid, and magnoid according to their respective correlations with gene expression patterns from histologically defined bronchioalveolar carcinoma, squamous cell carcinoma, and large-cell carcinoma. Tumor subtypes were distinguishable by many hundreds of genes, and lists generated in one cohort were predictive of tumor subtypes in the two other cohorts. Tumor subtypes correlated with clinically relevant covariates, including stage-specific survival and metastatic pattern. Most notably, bronchioid tumors were correlated with improved survival in early-stage disease, whereas squamoid tumors were associated with better survival in advanced disease.DNA microarray analysis of lung adenocarcinomas identified reproducible tumor subtypes which differ significantly in clinically important behaviors such as stage-specific survival.
Allergic sensitization and diet: ecological analysis in selected European cities
Authors: J. Heinrich, B. Hölscher, G. Bolte, G. Winkler
Journal: European Respiratory Journal (2001)

It has been postulated that the prevalence of atopic diseases and their increase over time are associated with regional differences in diet and trends. The results of an ecological correlation study comparing the mean daily intake of selected dietary constituents and the prevalence of allergic sensitization in adults in Europe is presented. Prevalence data from the European Community Respiratory Health Survey (ECRHS) were used. For eight out of 37 ECRHS centres (including 3,872 subjects), comparable dietary data could be obtained. The effect for each dietary constituent was modelled using logistic regression analyses with a term for over dispersion. Inverse associations between the prevalence of allergic sensitization and the energy adjusted intake of fruit were found (odds ratio (OR)=0.68, p=0.034). Furthermore OR for energy adjusted intake of vitamin A (OR=0.73, p=0.057), vitamin C (OR=0.83, p=0.338) and riboflavin (OR=0.72, p=0.077) were consistently &lt;1, but confidence intervals were wider. Daily intake of monounsaturated fatty acids (energy adjusted) was positively associated with sensitization prevalence (OR=1.59, p=0.035). These results support the hypothesis that a high intake of monounsaturated fatty acids might promote the development of allergic sensitization.
Geographic mitochondrial DNA variation in the rock hyrax, Procavia capensis.
Authors: P Prinsloo, T J Robinson
Journal: Molecular Biology and Evolution (1992)

Restriction-fragment-length polymorphisms in mitochondrial DNA (mtDNA) were used to evaluate geographic population genetic structure in the rock hyrax, Procavia capensis, a species which occurs widely, though restricted to rocky habitat, throughout South Africa. Ten restriction endonucleases were employed to assay mtDNAs from 55 specimens representing 10 localities. Haplotypes showed strong geographic patterning, and estimates of nucleotide sequence divergence indicate two major clades thought to be dispersing along separate routes. The divergence time of approximately 2 Myr between clades is relatively high for intraspecific variation. We speculate that the marked genetic break distinguishing the northwestern populations from those constituting the south/central clade may be indicative of two species in what has conventionally been regarded as P. capensis.
Graduate Medical Education and Patient Safety: A Busy—and Occasionally Hazardous—Intersection
Authors: Kaveh G. Shojania, Kathlyn E. Fletcher, Sanjay Saint
Journal: Annals of Internal Medicine (2006)

A patient admitted to a teaching hospital with a mild episode of acute pancreatitis initially improved, but then her condition deteriorated and she subsequently died. The initial deterioration probably reflected bowel obstruction, as shown on an abdominal radiograph that an on-call intern forgot to review. This diagnostic delay was compounded by poor communication that resulted in a medical student inserting a feeding tube--rather than a nasogastric tube--to decompress the bowel, followed by failure to recognize how ill the patient had become. The case highlights the hazards of patient handoffs as well as the importance of clear communication techniques and knowing when to ask for help. The discussion also shows the vicious circle that results when attending physicians fail to provide effective supervision: Not only is safety compromised but trainees lose the experience of being supervised. Consequently, trainees have no models of effective supervision on which to draw when they become supervisors. They then fall into the same trap as those who taught them, busying themselves with direct patient care and providing supervision only as time allows.
S49 Is the development of acute lung injury influenced by increased levels of IL17 as a result of Treg/TH17 imbalance?
Authors: R. C. A. Dancer, V. D'Souza, L. Jeffery, D. Sansom, C. R. Bassford, G. Perkins, D. R. Thickett
Journal: Thorax (2010)

<h3>Introduction</h3> Vitamin D is known to have profound effects on the immune system. We have shown that vitamin D is lower in patients with Acute Lung Injury (ALI) than in healthy or at risk controls and that in patients at risk of ALI post oesophagectomy, low vitamin D levels are associated with increased post-operative systemic inflammatory response and alveolar epithelial dysfunction. Studies have shown that when T cells are exposed to vitamin D, expression of IL17 decreases and regulatory capacity increases. We hypothesised that vitamin D deficiency may play a role in development of Acute Lung Injury (ALI) via changes in the balance between regulatory T cells (Treg) and pro-inflammatory Th17 cells. <h3>Methods</h3> Plasma levels of 25-OH Vitamin D (Tandem mass spectrometry) and 1,25-OH Vitamin D (ELISA)were measured in samples from patients with ALI. Normal T cells were exposed to BAL from patients with ALI with or without addition of exogenous vitamin D and determined frequencies of Treg and Th17 cells using flow cytometry. <h3>Results</h3> All samples tested had insufficient plasma levels of 25-OH vitamin D (&lt;75 nmol/l, median 14.1 nmol/l). 1,25 vitamin D levels ranged from &lt;20 to 176 pmol/l (reference range 43–144 pmol/l). 1,25 vitamin D levels were significantly related to both ITU survival (p=0.04) and survival at 90 days (p=0.04). Our initial findings suggest that BAL taken on day 0 of ARDS upregulated IL17 expression in normal T cells. This finding was blocked by exogenous 1,25-OH Vitamin D. By contrast, BAL taken on day 4 upregulated FoxP3 and CD25 expression, suggesting an increase in regulatory T cell activity. <h3>Discussion</h3> These results suggest that in early ARDS an imbalance in T cells favouring expression of IL-17 may play a role in the inflammatory response to injury, and this may be attenuated by adequate vitamin D levels. Later in the course of the disease, Treg cells may predominate and play a role in resolution.
Normal P50 Gating in Unmedicated Schizophrenia Outpatients
Authors: Sidse M Arnfred, Andrew C N Chen, Birte Y Glenthøj, Ralf P Hemmingsen
Journal: American Journal of Psychiatry (2003)

The hypothesis of a sensory gating defect in schizophrenia has been supported by studies demonstrating deficient auditory P50 gating in patients. P50 gating is the relative attenuation of P50 amplitude in the auditory evoked potential following the second auditory stimulus of a stimulus pair.Auditory evoked potentials of 12 unmedicated male patients with schizophrenia and 24 healthy men were recorded during three runs of 40 click pairs. Three alternative waveform-processing strategies were used to analyze the data.Regardless of strategy used, the differences between subject groups regarding P50 amplitude and gating were nonsignificant.The P50 gating in the patient group was normal. The results do not support the concept of the P50 gating defect as a general trait marker of schizophrenia.
Prevention of Gastric Cancer
Authors: Rolando Herrero, Julie Parsonnet, Edwin Robert Greenberg
Journal: JAMA (2014)

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Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma
Authors: Clara Montagut, Sreenath V. Sharma, Toshi Shioda, Ultan McDermott, Matthew Ulman, Lindsey E. Ulkus, Dora Dias-Santagata, Hannah Stubbs, Diana Y. Lee, Anurag Singh, Lisa Drew, Daniel A. Haber, Jeffrey Settleman
Journal: Cancer Research (2008)

Abstract Activating BRAF kinase mutations arise in ∼7% of all human tumors, and preclinical studies have validated the RAF–mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase–ERK signaling cascade as a potentially important therapeutic target in this setting. Selective RAF kinase inhibitors are currently undergoing clinical development, and based on the experience with other kinase-targeted therapeutics, it is expected that clinical responses to these agents, if observed, will lead to the eventual emergence of drug resistance in most cases. Thus, it is important to establish molecular mechanisms underlying such resistance to develop effective therapeutic strategies to overcome or prevent drug resistance. To anticipate potential mechanisms of acquired resistance to RAF inhibitors during the course of treatment, we established drug-resistant clones from a human melanoma-derived cell line harboring the recurrent V600E activating BRAF mutation, which exhibits exquisite sensitivity to AZ628, a selective RAF kinase inhibitor. We determined that elevated CRAF protein levels account for the acquisition of resistance to AZ628 in these cells, associated with a switch from BRAF to CRAF dependency in tumor cells. We also found that elevated CRAF protein levels may similarly contribute to primary insensitivity to RAF inhibition in a subset of BRAF mutant tumor cells. Interestingly, AZ628-resistant cells demonstrating either primary drug insensitivity or acquired drug resistance exhibit exquisite sensitivity to the HSP90 inhibitor geldanamycin. Geldanamycin effectively promotes the degradation of CRAF, thereby revealing a potential therapeutic strategy to overcome resistance to RAF inhibition in a subset of BRAF mutant tumors. [Cancer Res 2008;68(12):4853–61]
Endothelial SRF/MRTF ablation causes vascular disease phenotypes in murine retinae
Authors: Christine Weinl, Heidemarie Riehle, Dongjeong Park, Christine Stritt, Susanne Beck, Gesine Huber, Hartwig Wolburg, Eric N. Olson, Mathias W. Seeliger, Ralf H. Adams, Alfred Nordheim
Journal: Journal of Clinical Investigation (2013)

Retinal vessel homeostasis ensures normal ocular functions. Consequently, retinal hypovascularization and neovascularization, causing a lack and an excess of vessels, respectively, are hallmarks of human retinal pathology. We provide evidence that EC-specific genetic ablation of either the transcription factor SRF or its cofactors MRTF-A and MRTF-B, but not the SRF cofactors ELK1 or ELK4, cause retinal hypovascularization in the postnatal mouse eye. Inducible, EC-specific deficiency of SRF or MRTF-A/MRTF-B during postnatal angiogenesis impaired endothelial tip cell filopodia protrusion, resulting in incomplete formation of the retinal primary vascular plexus, absence of the deep plexi, and persistence of hyaloid vessels. All of these features are typical of human hypovascularization-related vitreoretinopathies, such as familial exudative vitreoretinopathies including Norrie disease. In contrast, conditional EC deletion of Srf in adult murine vessels elicited intraretinal neovascularization that was reminiscent of the age-related human pathologies retinal angiomatous proliferation and macular telangiectasia. These results indicate that angiogenic homeostasis is ensured by differential stage-specific functions of SRF target gene products in the developing versus the mature retinal vasculature and suggest that the actin-directed MRTF-SRF signaling axis could serve as a therapeutic target in the treatment of human vascular retinal diseases.
Popliteal Vein Aneurysm With Recurrent Pulmonary Thromboemboli
Authors: James R. Dahl
Journal: JAMA (1976)

PULMONARY thromboembolism has been the subject of excellent reviews.<sup>1-3</sup>In none of these, however, could we find mention of peripheral venous aneurysm as an underlying cause of this disorder. We report such a case. <h3>Report of a Case</h3> A 59-year-old housewife was brought to the emergency room because of a sudden onset of severe pain in her left leg, which was preceded by dyspnea of two days' duration. She appeared lethargic and cyanotic. Her blood pressure was 140/90 mm Hg, her pulse rate was 120 beats per minute with frequent premature ventricular contractions, and her respirations were 16/min. Her left leg was pallid, cool, and pulseless beyond the femoral level. Although a popliteal artery embolus was diagnosed immediately, embolectomy was deferred until her cardiopulmonary status had been further clarified and stabilized. On admission to the ward, her hematocrit reading was 41% and her leukocyte count was 11,300/cu mm, with
Wt1 and Retinoic Acid Signaling in the Subcoelomic Mesenchyme Control the Development of the Pleuropericardial Membranes and the Sinus Horns
Authors: Julia Norden, Thomas Grieskamp, Ekkehart Lausch, Bram van Wijk, Maurice J.B. van den Hoff, Christoph Englert, Marianne Petry, Mathilda T.M. Mommersteeg, Vincent M. Christoffels, Karen Niederreither, Andreas Kispert
Journal: Circulation Research (2010)

The cardiac venous pole is a common focus of congenital malformations and atrial arrhythmias, yet little is known about the cellular and molecular mechanisms that regulate its development. The systemic venous return myocardium (sinus node and sinus horns) forms only late in cardiogenesis from a pool of pericardial mesenchymal precursor cells.To analyze the cellular and molecular mechanisms directing the formation of the fetal sinus horns.We analyzed embryos deficient for the Wt1 (Wilms tumor 1) gene and observed a failure to form myocardialized sinus horns. Instead, the cardinal veins become embedded laterally in the pleuropericardial membranes that remain tethered to the lateral body wall by the persisting subcoelomic mesenchyme, a finding that correlates with decreased apoptosis in this region. We show by expression analysis and lineage tracing studies that Wt1 is expressed in the subcoelomic mesenchyme surrounding the cardinal veins, but that this Wt1-positive mesenchyme does not contribute cells to the sinus horn myocardium. Expression of the Raldh2 (aldehyde dehydrogenase family 1, subfamily A2) gene was lost from this mesenchyme in Wt1(-/-) embryos. Phenotypic analysis of Raldh2 mutant mice rescued from early cardiac defects by retinoic acid food supply revealed defects of the venous pole and pericardium highly similar to those of Wt1(-/-) mice.Pericardium and sinus horn formation are coupled and depend on the expansion and correct temporal release of pleuropericardial membranes from the underlying subcoelomic mesenchyme. Wt1 and downstream Raldh2/retinoic acid signaling are crucial regulators of this process. Thus, our results provide novel insight into the genetic and cellular pathways regulating the posterior extension of the mammalian heart and the formation of its coelomic lining.
Determination of future prevention strategies in elite track and field: analysis of Daegu 2011 IAAF Championships injuries and illnesses surveillance
Authors: Juan-Manuel Alonso, Pascal Edouard, Giuseppe Fischetto, Bob Adams, Frédéric Depiesse, Margo Mountjoy
Journal: British Journal of Sports Medicine (2012)

To determine the incidence and characteristics of newly incurred injuries and illnesses during international Athletics Championships, by improving the medical surveillance coverage, in order to determine future prevention strategies.Prospective recording of newly occurred injuries and illnesses.13th International Association of Athletics Federations World Championships in Athletics 2011 in Daegu, Korea.National team and Local Organising Committee physicians; and 1851 registered athletes.Incidence and characteristics of newly incurred injuries and illnesses.82% of athletes were covered by medical teams participating with a response rate of 94%. A total of 249 injuries were reported, representing an incidence of 134.5 injuries per 1000 registered athletes, and 119 (48%) resulted in time loss from sport. A total of 185 injuries affected the lower limb (74%). Hamstring strain was the main diagnosis and 67% resulted in absence from sport. Overuse (n=148; 59%) was the predominant cause. A total of 126 illnesses were reported, signifying an incidence of 68.1 per 1000 registered athletes. Upper respiratory tract infection was the most common reported diagnosis (18%), followed by exercise-induced dehydration (12%), and gastroenteritis/diarrhoea (10%). The highest incidences of injuries were found in combined events and middle and long-distance events, and of illness in race walking events.During elite Athletics World Championships, 135 injuries, 60 time-loss injuries and 68 illnesses per 1000 registered athletes were reported. Higher risks of injuries were found in combined events and long-distance runs. Preventive interventions should focus on overuse injuries and hamstring strains, decreasing the risk of transmission of infectious diseases, appropriate event scheduling and heat acclimatisation.
Effect of exercise on erythrocyte count and blood activity concentration after technetium-99m in vivo red blood cell labeling.
Authors: M A Konstam, S Tu'meh, J Wynne, J R Beck, J Kozlowski, B L Holman
Journal: Circulation (1982)

We studied the effect of exercise on blood radiotracer concentration after technetium-99m in vivo red blood cell labeling. After red blood cell labeling, 13 subjects underwent maximal supine bicycle exercise. Radioactivity, analyzed with a well counter, was measured in heparinized venous blood samples drawn at rest and during peak exercise. Changes in activity were compared with changes in erythrocyte count. Activity and erythrocyte counts increased during exercise in all 13 subjects. Percent increase in activity correlated with percent increase in erythrocyte count (r = -0.78), but did not correlate with either duration of exercise or maximal heart rate. Twenty minutes after termination of exercise, activity and erythrocyte count had decreased from peak exercise values but remained higher than preexercise values. In nine nonexercised control subjects, samples drawn 20 minutes apart showed no change in activity or in erythrocyte count. We conclude that exercise increases blood activity, primarily because of an increase in erythrocyte count. During radionuclide ventriculography, blood activity must be measured before and after any intervention, particularly exercise, before a change in left ventricular activity can be attributed to a change in left ventricular volume.
Endobronchial ultrasound and fluoroscopy in the study of peripheral lung lesions
Authors: Albert Sánchez-Font, Laia Giralt, Rodrigo Alcántara, Javier Gimeno, Lara Pijuan, Ivan Vollmer, Joaquim Gea, Víctor Curull
Journal: European Respiratory Journal (2011)

Introduction:  Endobronchial ultrasound (EBUS) is a minimally invasive technique that expands the view of the bronchoscopist beyond the lumen of the airway. Radial probe EBUS (rEBUS) is used for the detection of peripheral lung lesions.   Aim:  To analyze the diagnostic yield of rEBUS in peripheral pulmonary lesions.   Methods:  All patients which  underwent bronchoscopy  to study peripheral lung lesions from January 2009 to February 2011 were prospectively included. Patients were randomly distributed in two groups: fluoroscopy and rEBUS (30 patients, 70.4±7.8 years) or fluoroscopy alone (64 patients, 68.1±10.9 years). All procedures were performed under fluoroscopic guidance with iv conscious sedation. rEBUS was performed using an endoscopic ultrasound system (EU-M60, Olympus, Tokyo, Japan), equipped with a 20-MHz mechanical radial type miniature probe (UM-BS S20-17S). Bronchoscopist, cytologist, study protocol, techniques and tools were the same ones throughout the whole study.   Results:  94 patients (68.9±10 years) with peripheral pulmonary lesions suspicious of malignancy were studied. The average size of these lesions was 35.2±13.6 mm in rEBUS group vs 41.8±19.6 mm in fluoroscopy group (n.s). In 26 cases (27.6%) the size was    Conclusions:  rEBUS is a promising, useful and safe technique for the diagnosis of peripheral pulmonary lesions, especially in those of small size.