tbuckley/cabot-search huggingface dataset:
GE-07 * THE GENOMIC LANDSCAPE OF DIVERSE BRAIN TUMORS REVEALS KNOWN AND NOVEL ONCOGENIC ALTERATIONS FREQUENTLY ASSOCIATED WITH SENSITIVITY TO TARGETED INHIBITORS
Authors: J. Chmielecki, G. Frampton, D. Morosini, S. Ali, D. Lipson, R. Yelensky, J. Ross, V. Miller, P. Stephens
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain tumors are complex cancers that range in behavior from aggressive to indolent. While some oncogenic alterations have been identified in these tumors, the efficacy of molecularly-matched targeted therapies has not been established. We sought to explore the spectrum of genomic alterations in a large unselected clinical collection of brain tumors (n = 282), and to determine the potential therapeutic actionability in these diseases. METHODS: FoundationOne® was used to characterize comprehensively all classes of genomic alterations in 236 cancer-related genes plus 19 genes frequently rearranged in cancer. Captured DNA was sequenced to average median depth of 696x, and resultant sequences were assessed for base substitutions, insertions and deletions, copy number changes, and select rearrangements. RESULTS: This collection consisted of glioblastoma (58.5%), astrocytoma (13.1%), anaplastic astrocytoma (12.4%), oligodendroglioma (9.2%), glioma (6.4%), and gliosarcoma (0.4%). Ninety-six percent (96%) of cases harbored at least one alteration associated with an approved agent or an agent in clinical trials. Activating genomic alterations included rearrangements, amplification, and/or mutations in EGFR, BRAF, PDGFRA, MET, KIT, FGFR3, and KRAS. Recurrent loss of function alterations were identified in TP53, CDKN2A/B, ATRX, NF1, and RB1, among others. Co-occurring alterations in the DNA helicase ATRX and the gene encoding IDH1 were also observed frequently. Interestingly, we identified a FIP1L1-PDGFRA fusion in a glioblastoma, and multiple BRAF fusions in anaplastic astrocytoma. CONCLUSIONS: Genomic alterations associated with an FDA-approved or investigational agents are frequent in brain cancers. Although the efficacy of molecularly-matched therapies has yet to be established in these tumors, converging clinical evidence suggest potential clinical utility. The FIP1L1-PDGFRA fusion identified in a glioblastoma is associated with remarkable sensitivity to imatinib in hypereosinophilic syndrome, and BRAF fusions in other diseases are responsive to combination targeted therapy. These data suggest that comprehensive genomic profiling can identify potential targets for personalized therapies in these tumors.
Health Policy Basics: Physician Quality Reporting System
Authors: Michelle K. Koltov, Nitin S. Damle
Journal: Annals of Internal Medicine (2014)

The U.S. health care system is in the midst of transforming from a fee-for-service system to a value-based system that delivers high-quality and cost-effective care. Quality reporting programs and increasing transparency of performance are meant to encourage physicians and hospitals to invest in improving the delivery of care. In 2006, the Centers for Medicare & Medicaid Services implemented the Physician Quality Reporting System (PQRS). The PQRS is an incentive and penalty payment program for eligible professionals who report data on quality measures for covered professional services furnished to Medicare beneficiaries. The program gives eligible professionals the opportunity to assess the quality of care they are providing to their patients and compare their performance on a given measure with that of their peers. This article discusses the history of PQRS, the 2014 PQRS, and how it affects other quality programs.
Did They Just Prove That a Diagnosis of “Septic Shock” Is Meaningless?
Authors: Theodore J. Iwashyna, Sushant Govindan
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Antibiotics Might Do More Than Cause ResistanceAntibiotics have revolutionized medicine, and the success of many modern treatment approaches, such as transplantation, prolonged and intensive immunosuppression, and treatment in intensive care units (ICUs), would be significantly reduced without these miracle drugs.Yet, the use of antibiotics comes at a price, which is the selection of antibiotic resistance.This natural process in bacteria in
Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia
Authors: M Tsurusawa, Y Shimomura, K Asami, A Kikuta, A Watanabe, Y Horikoshi, T Matsushita, H Kanegane, S Ohta, A Iwai, H Mugishima, S Koizumi
Journal: Leukemia (2009)
Imatinib-ULS-lysozyme: A proximal tubular cell-targeted conjugate of imatinib for the treatment of renal diseases
Authors: M.E.M. Dolman, K.M.A. van Dorenmalen, E.H.E. Pieters, M. Lacombe, J. Pato, G. Storm, W.E. Hennink, R.J. Kok
Journal: Journal of Controlled Release (2011)
Intestinal Polyposis and Pigmentation of the Lip
Authors: E. L. Crumpacker
Journal: New England Journal of Medicine (1955)

THE strange association of intestinal polyposis and melanotic spots of the oral mucous membranes was unrecognized in the English and American literature as a syndrome of diagnostic significance until recently.With their classic description in 1949, Jeghers and his co-workers1 alerted the medical profession to the puzzling association of these two rare conditions. These authors exhaustively reviewed previous articles in the world literature. Subsequent reports through January, 1954, have been reviewed.2 An additional case has been reported by Bruwer, Bargen and Kier-land,3 who suggested the eponym, Peutz-Jeghers syndrome, for the condition, since Peutz4 made the original observation and Jeghers et . . .
Bicarbonate absorption stimulates active calcium absorption in the rat proximal tubule.
Authors: K Bomsztyk, M B Calalb
Journal: Journal of Clinical Investigation (1988)

To evaluate the effect of luminal bicarbonate on calcium reabsorption, rat proximal tubules were perfused in vivo. Perfusion solution contained mannitol to reduce water flux to zero. Total Ca concentration was measured by atomic absorption spectrometry, Ca ion concentration in the tubule lumen (CaL2+) and the peritubular capillary (CaP2+), and luminal pH (pHL) with ion-selective microelectrodes and transepithelial voltage (VTE) with conventional microelectrodes. When tubules were perfused with buffer-free Cl-containing solution, net Ca absorption (JCa) averaged 3.33 pmol/min. Even though VTE was 1.64 mV lumen-positive, CaL2+, 1.05 mM, did not fall below the concentration in the capillary blood, 1.07 mM. When 27 mM of Cl was replaced with HCO3, there was luminal fluid acidification. Despite a decrease in VTE and CaL2+, JCa increased to 7.13 pmol/min, indicating that the enhanced JCa could not be accounted for by the reduced electrochemical gradient, delta CCa. When acetazolamide or an analogue of amiloride was added to the HCO3 solution, JCa was not different from the buffer-free solution, suggesting that HCO3-stimulated JCa may be linked to acidification. To further test this hypothesis, we used 27 mM Hepes as the luminal buffer. With Hepes there was luminal fluid acidification and JCa was not different from the buffer-free solution but delta CCa was significantly reduced, indicating enhanced active calcium transport. We conclude from the results of the present study that HCO3 stimulates active Ca absorption, a process that may be linked to acidification-mediated HCO3 absorption.
Sterilisation and the mentally handicapped.
Authors: D Chakraborti
Journal: BMJ (1987)

the test therefore picks out all but the most sophisticated malingerers because most choose wrong answers throughout and score near zero.Normal people identify 35-40 correctly, and patients with partial anosmia score 15-35.One advantage is that after simple instruction the patient can perform the test unsupervised.Also available are sets of plastic squeeze bottles producing serial dilutions of pyridine vapour.4These measure the threshold concentration at which an odour can be detected, but for the non-specialist centre this test has little advantage over the scratch and sniff tests.Finally, merely testing the sense of smell is not synony- mous with investigating a complaint of olfactory disorder.All patients need a history taken and examination performed, with particular reference to neurological and nasopharyngeal problems.When no cause can be found for demonstrable olfactory loss, or when the patient's complaint persists despite negative findings on simple tests, referral to a specialist centre for more detailed assessment is necessary.Smell, the Cinderella ofthe senses, should be taken seriously.
More on Screening for Mild Thyroid Failure-Reply
Authors: Mark D. Danese
Journal: JAMA (1997)

In Reply.  —Dr Helfand points out that it is not possible to know in advance which symptomatic patients with mild thyroid failure will respond to thyroxine sodium therapy. He questions the precise benefit achieved from symptom relief in our decision and cost-effectiveness analysis and the impact that uncertainty regarding the reversibility of symptoms has on the final results.  We have considered this issue further and find that it has little effect on the results of the model for 3 reasons. First, relatively few patients were treated for potentially reversible symptoms alone. Because there are no data regarding overlap of the 3 treatment indications—reversible symptoms (28% of patients), antithyroid antibodies predicting progression of disease (67% of women, 40% of men), and hypercholesterolemia (25% of patients)—we assumed that these treatment indications were independently associated in patients with mild thyroid failure. Consequently, most patients with symptoms also had another indication for treatment; only 6% of
Proteolysis of Tissue Factor Pathway Inhibitor-1 by Thrombolysis in Acute Myocardial Infarction
Authors: Ilka Ott, Valerie Malcouvier, Albert Schömig, Franz-Josef Neumann
Journal: Circulation (2002)

Background — In acute myocardial infarction (AMI), surface-bound tissue factor pathway inhibitor-1 (TFPI-1) inhibits an increased monocyte procoagulant activity. In addition, TFPI-1 is released from microvascular endothelial cells after treatment with heparin and thereby contributes to its antithrombotic properties. Methods and Results — We examined 19 patients in a randomized study comparing intravenous fibrinolysis with alteplase (n=9) and revascularization by stent placement with additional abciximab treatment (n=10). We obtained blood samples for analysis of monocytic TFPI-1 surface expression by flow cytometry and plasma TFPI-1 concentrations by immunoassay before and after therapy. We found a significant decrease in surface TFPI-1 on circulating monocytes 24 hours after thrombolysis ( P =0.006) that was not observed after stenting. Systemic plasma TFPI-1 concentrations increased immediately after stenting by 71±14% ( P =0.008), whereas after thrombolysis, a decrease in TFPI-1 plasma concentrations of 21±11% was observed ( P =0.075). In vitro experiments confirmed that plasmin decreased TFPI-1 surface expression dose-dependently. Conclusions — Activation of the fibrinolytic system by alteplase in AMI decreases surface-associated TFPI-1 on circulating monocytes and plasma TFPI-1. Reduced TFPI-1 may contribute to thrombotic complications after fibrinolysis in AMI.
Superior-Mesenteric-Artery Embolectomy in the Treatment of Massive Mesenteric Infarction
Authors: Robert S. Shaw, Robb H. Rutledge
Journal: New England Journal of Medicine (1957)

EMBOLIC occlusion of the main trunk of the superior mesenteric artery produces severe ischemia of the entire bowel between the terminal duodenum and mid-transverse colon. This entity must be differentiated from small emboli to branches of the artery that either produce no change, owing to the rich collateral circulation of the intestinal arcades, or cause necrosis of a limited segment of bowel, which can be dealt with satisfactorily by surgical resection. Collateral circulation after obstruction of the main trunk is derived from the celiac axis and inferior mesenteric artery, and where occlusion of the superior mesenteric artery occurs gradually, it . . .
Role of P1 purinergic receptors in myocardial ischemia sensory transduction
Authors: G Thompson
Journal: Cardiovascular Research (2002)

Objectives: To characterize the role that cardiac sensory P1 purinergic (adenosine A1 or A2) receptors play in transducing myocardial ischemia. Methods: Porcine nodose ganglion cardiac sensory neuron adenosine A1 or A2 receptor function was studied in situ during control states as well as in the presence of the peptides bradykinin and substance P or focal ventricular ischemia. The responses of porcine nodose ganglion cardiac and non-cardiac afferent neuronal somata to adenosine were also studied in vitro. Results: Local application of A1 or A2 adenosine receptor agonists modified the activity generated by ventricular sensory neurites associated with 70 and 74% of identified nodose ganglion cardiac afferent somata in situ, respectively, exciting most neurons. In contrast, adenosine reduced the excitability of nodose ganglion cardiac afferent neuronal somata in vitro. Bradykinin and substance P affected 56 and 63%, respectively, of tested afferent neurons. The capacity of ventricular sensory neurites to transduce signals relating to these peptides was virtually eliminated by the presence of P1 purinergic receptor antagonists. So was their capacity to transduce focal ventricular ischemia. Since most cardiac sensory neurites responded differently to adenosine in vivo than did cardiac afferent neuronal somata in vitro, it appears that the transduction properties of cardiac afferent neurons need to be characterized in situ. Conclusions: Most ventricular sensory neurites associated with nodose ganglion afferent neurons possess adenosine A1 and/or A2 receptors that play a primary role in transducing myocardial ischemic events to central neurons. These data support clinical observations implicating cardiac sensory purinoceptors in transducing myocardial ischemic events.
Characterization of the nail matrix basement membrane zone: an immunohistochemical study of normal nails and of the nails in Herlitz junctional epidermolysis bullosa
Authors: N. Cameli, M. Picardo, A. Pisani, J. P. Ortonne, A. Tosti
Journal: British Journal of Dermatology (1996)

Journal Article Characterization of the nail matrix basement membrane zone: an immunohistochemical study of normal nails and of the nails in Herlitz junctional epidermolysis bullosa Get access N. Cameli, N. Cameli Department of Dermatology. University of Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Picardo, M. Picardo Department of Dermatology. San Gallicano, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Pisani, A. Pisani Laboratory of Dermatological Research, University of Nice, France Search for other works by this author on: Oxford Academic Google Scholar J. P. Ortonne, J. P. Ortonne Laboratory of Dermatological Research, University of Nice, France Search for other works by this author on: Oxford Academic Google Scholar A. Tosti A. Tosti Department of Dermatology. University of Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 1, 1 January 1996, Pages 182–184, https://doi.org/10.1111/j.1365-2133.1996.tb07866.x Published: 01 January 1996
4-Phenylbutyrate modulates ubiquitination of hepatocanalicular MRP2 and reduces serum total bilirubin concentration
Authors: Hisamitsu Hayashi, Tadahaya Mizuno, Reiko Horikawa, Hironori Nagasaka, Takashi Yabuki, Hajime Takikawa, Yuichi Sugiyama
Journal: Journal of Hepatology (2012)
SPRAY RESIDUE POISONING FROM STRING BEANS
Authors: J. C. Geiger
Journal: JAMA (1933)

<h3>To the Editor:</h3> —Spray residue poisoning, in man, occurs with some frequency. A recent instance in San Francisco is worthy of note: Mrs. M., a housewife, served a meal consisting of string beans, summer squash, boiled rice, dried cooked peaches, and, to one individual only, broiled steak. Seven people, including three children of 10, 6 and 2 years, and four adults were served. Mrs. M. was the only one affected, but also she was the one of the group who ate an additional portion of the string beans, an incident occurring about one hour after the meal. Physical signs and symptoms complained of included nausea, vomiting, diarrhea, headache, abdominal pain, and "dark spots before the eyes." The disturbance endured through three days for forty-eight hours. Samples of the beans were obtained from the market and were prepared in the same aluminum vessel as before, and chemical studies revealed lead to
Help a Snorer
Authors: George D. McGeary
Journal: JAMA (1981)

<h3>To the Editor.—</h3> E. L. C. Broomes, MD (1980;244:1783), suggests a cervical collar to prevent snoring. It probably works, but for years I prescribed a much simpler solution that is less likely to keep you awake. It was suggested by my grandmother, who sewed a small glass marble into the pajama top between the shoulder blades under a scrap of cloth. When the snorer rolls on his or her back, he immediately rolls back on his side or abdomen, usually without waking, or with half-wakening, and resumes sleep without snoring. Once a marble is sewed in each pajama top, the marble can be forgotten, as they go through the wash without problem, and they are less likely to be left behind on trips.
Kidneys for Transplantation
Authors: A. O. Frank
Journal: BMJ (1974)

correct period.The skewness of the distribu- tion suggests a bias towards slower rather than more rapid rates.Surprisingly perhaps this bias seems less evident when the solutions contained additives, though in this subgroup the proportion of correctly administered solutions was higher.It seems likely that the methods used in our survey will underestimate the true extent and size of variations in rate.Because we measured only the mean infusion rate shortterm decreases or increases would be missed.Attempts to correct these variations are commonly encountered in the ward as efforts to "get the bottle through in time" or to "slow it down a bit until we have someone free to change it."We look forward to hearing about the servo-controlled regulating clamp mentioned by Drs.Flack and Whyte, which will take a little of the uncertainty out of intravenous infusion therapy.-Weare, etc.,
Margo's Logo
Authors: Andrew D. Firlik
Journal: JAMA (1991)

If she stands as straight as she can, Margo measures nearly five feet tall. Ordinarily, though, her spine assumes the curve of her wooden rocking chair, arching her over like an unwatered houseplant. Margo is 55 years old. If you ever saw her ambling unsteadily down the street on a windy day, a knit scarf whipping at her neck, something might compel you to cross the street, walk up behind her, and get ready to catch her in case an especially strong gust blew her off her feet. That's sort of what happened to me. I met Margo last summer during a gerontology elective after my first year in medical school. Margo has Alzheimer's disease. Like her body, her mind is shrinking. I observed Margo, leaning into winds of her disease, fighting them off; Alzheimer's blows a relentless course. So I crossed the street. I became close to Margo. I
Changes in structure and peptidase activity of rat small intestine induced by prednisolone
Authors: A. J. Wall, T. J. Peters
Journal: Gut (1971)

Chronic dietary administration of prednisolone to the adult rat caused alteration in morphology and enzyme activity of the small intestinal mucosa. Reduction of villous height, crypt depth, and surface epithelial cell height was accompanied by a significant increase in the specific activity of several jejunal peptidases.
Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY.
Authors: R A Goodlad, W Lenton, M A Ghatei, T E Adrian, S R Bloom, N A Wright
Journal: Gut (1987)

Refeeding starved rats with a fibre free 'elemental' diet increased crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was seen when inert bulk (kaolin) was added to the 'elemental' diet. Addition of a poorly fermentable dietary 'fibre' (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable 'fibre' (purified wheat bran) caused a large proliferative response in the proximal, mid and distal colon and in the distal small intestine. A gel forming 'fibre' also stimulated proliferation in the distal colon. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus, whilst inert bulk cannot stimulate colonic epithelial cell proliferation, fermentable 'fibre' is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.
Alpha-chain Disease with Clinical, Immunological, and Histological Recovery
Authors: O. N. Manousos, J. C. Economidou, D. E. Georgiadou, K. G. Pratsika-Ougourloglou, S. J. Hadziyannis, G. E. Merikas, K. Henry, W. F. Doe
Journal: BMJ (1974)

Clinical, immunological, and histological recovery in a patient with alpha-chain disease is described. The patient, a 27-year-old Greek man, presented with severe steatorrhoea, abdominal pain, oedema, and hypogammaglobulinaemia. Treatment with tetracycline produced only temporary remission. Intermittent therapy with prednisone and cyclophosphamide together with antibiotics was followed by clinical recovery, return of histological appearances of the small intestine to normal, and disappearance of free alpha-chain protein from the serum. The patient remained well one year later without treatment.
NICE requires primary care trusts to tackle prevention and management of obesity
Authors: Susan Mayor
Journal: BMJ (2006)

All primary care trusts must ensure that systems are in place to allow health professionals to implement interventions to prevent and treat obesity, the first national guidance from the National Institute for Health and Clinical Excellence (NICE) on obesity in adults and children in England and Wales says. 

The guidance was developed by the National Collaborating Centre for Primary Care, a group of healthcare professions based at the Royal College of General Practitioners, and NICE's Centre for Public Health Excellence. It aims to stem the rising prevalence of obesity and associated diseases, to increase the effectiveness of interventions to prevent overweight and obesity, and to improve the care provided to adults and children with obesity, particularly in primary care. 

James McEwan, emeritus professor of public health at the University of Glasgow and chairman of the guidance development group, said: “In the past, there …