tbuckley/cabot-search huggingface dataset:
The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing
Authors: Teresa Helsten, Sheryl Elkin, Elisa Arthur, Brett N. Tomson, Jennifer Carter, Razelle Kurzrock
Journal: Clinical Cancer Research (2015)

Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types.We analyzed frequencies of FGFR aberrations in 4,853 solid tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One.FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplification (66% of the aberrations), followed by mutations (26%) and rearrangements (8%). FGFR1 (mostly amplification) was affected in 3.5% of 4,853 patients; FGFR2 in 1.5%; FGFR3 in 2.0%; and FGFR4 in 0.5%. Almost every type of malignancy examined showed some patients with FGFR aberrations, but the cancers most commonly affected were urothelial (32% FGFR-aberrant); breast (18%); endometrial (∼13%), squamous lung cancers (∼13%), and ovarian cancer (∼9%). Among 35 unique FGFR mutations seen in this dataset, all but two are found in COSMIC. Seventeen of the 35 are known to be activating, and 11 are transforming.FGFR aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. These data suggest that FGFR inhibition could be an important therapeutic option across multiple tumor types.
Physical Activity Is Key for Successful Aging—Reply
Authors: Hannah Arem, Charles E. Matthews, I-Min Lee
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes
Authors: E. Rácz, E.P. Prens, M. Kant, E. Florencia, N.G. Jaspers, J.D. Laman, D. de Ridder, L. van der Fits
Journal: British Journal of Dermatology (2010)

The mode of action of narrowband ultraviolet B (NB-UVB) therapy in clearing psoriasis is incompletely understood, and in vivo studies at the molecular level in patients undergoing NB-UVB therapy are limited. We previously demonstrated increased expression and activity of double-stranded RNA (dsRNA) receptors in psoriasis lesions, and suggested that this enhanced innate signalling contributed to the maintenance of psoriatic inflammation.We investigated whether NB-UVB affects dsRNA receptor expression and function in vivo as well as in vitro.Skin samples of patients with psoriasis undergoing NB-UVB treatment were analysed for epidermal messenger RNA (mRNA) expression of the various dsRNA receptors by microarray and quantitative reverse transcription-polymerase chain reaction. Primary human keratinocytes were irradiated with NB-UVB and stimulated with interferon (IFN)-α or IFN-γ, critical cytokines in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic acid was used to assess the functional responsiveness of the cells to dsRNA.NB-UVB therapy of patients with psoriasis resulted in a significantly reduced mRNA expression of the activating dsRNA receptors MDA5 (IFIH1) and RIG-I (DDX58). On the other hand, expression of LGP2 (DHX58), toll-like receptor 3 (TLR3) and PKR (EIF2AK2) was not affected. In vitro, NB-UVB irradiation completely blocked the upregulation of four of the dsRNA receptors in primary human keratinocytes stimulated with IFN-α or IFN-γ, resulting in an attenuated inflammatory response to dsRNA.Our results show that NB-UVB irradiation inhibits the local innate inflammatory response to dsRNA, and suggest a novel mechanism of action of NB-UVB phototherapy in psoriasis.
Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.
Authors: M Wiesenfeld, M J O'Connell, H S Wieand, N J Gonchoroff, J H Donohue, R J Fitzgibbons, J E Krook, J A Mailliard, J B Gerstner, R Pazdur
Journal: Journal of Clinical Oncology (1995)

PURPOSE The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival. PATIENTS AND METHODS Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients. RESULTS With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P &lt; .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P &lt; .01) and Fc receptors (P &lt; .001) on peripheral-blood monocytes. CONCLUSION This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.
Update: influenza activity - United States, September 28, 2008-January 31, 2009.
Authors: L. Brammer, S. Epperson, L. Blanton, R. Dhara, T. Wallis, L. Finelli, A. Fiore, L. Gubavera, J. Bresee, A. Klimov, N. Cox, C. Reed
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Effects of Low-Level X-Radiation on 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Lingual Tumors in Syrian Golden Hamsters&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: A G Lurie, L S Cutler
Journal: JNCI Journal of the National Cancer Institute (1979)

The effects of repeated low-dose-rate, high-dose-rate X-radiation of the head and neck on lingual tumor induction by 7,12-dimethylbenz[a]anthracene (DMBA) in Syrian golden hamsters were studied. Animals received either topical application as 0.5% DMBA in acetone on the lateral middle third of the tongue three times a week for 15 consecutive weeks, 20-R X-radiation exposures of the head and neck once a week for 15 consecutive weeks, or concurrent radiation and DMBA treatments for 15 consecutive weeks. Animals were examined visually at regular intervals, and all were killed 35 weeks after the start of treatments. All tissues were than examined histopathologically. Animals receiving radiation alone had no detectable changes. Animals receiving DMBA plus radiation had an excess of papillomas compared to animals receiving only DMBA (35% vs. 15%). In addition, an excess of nonlingual oral tumors (lip, gingiva, and floor of mouth) was found in DMBA-treated plus radiation-treated animals versus DMBA-treated animals. These results suggest that repeated, localized, low-level X-radiation exposures enhance chemical tumorigenesis in a variety of oral tissues of Syrian golden hamsters.
Why Doctors get Angry in Crown Courts
Authors: Evan Whitton
Journal: Journal of the Royal Society of Medicine (2001)

The adversary system is even more unjust than Mr John Kirkham (March 2001 JRSM, p. 157) imagines. It is defined as a system controlled by lawyers, not judges. Geoffrey Robertson QC says it is a game and shouldn't be. Arthur Applbaum, Professor of Ethics at Harvard, says ‘lawyers might accurately be described as serial liars because they repeatedly try to induce others to believe in the truth of propositions, or in the validity of arguments, that they believe to be false’. (Hence my forthcoming work: Serial Liars: The Musical.) A US jurist, Murray L Schwartz, says: ‘...a lawyer is neither legally, professionally, nor morally accountable for the means used or the ends achieved’ on behalf of clients. In the opinion of a Sydney psychiatrist, Dr Elizabeth O'Brien, this remark sounds like psychopathy. The adversary system may thus be redefined as a game controlled by serial liars trained by legal academics to act as if they are psychopaths. I therefore trust that the British medical profession will support M Lionel Jospin's 1 June call for a common criminal justice system throughout the European Union. That will mean the beginning of the end for the adversary game and acceptance of the truth-based and (trained) judge-controlled system which was rejected nearly 800 years ago by a dozen or so probably corrupt London judges and lawyers.
Differences in volatile organic compounds (VOC) determined in exhaled breath in two populations of lung cancer (LC): With and without COPD
Authors: Mª Angeles Munoz-Lucas, Carolin Wagner-Struwing, Javier Jareno-Esteban, Javier de Miguel-Diez, Belen Carrillo-Aranda, Carlos Gutierrez-Ortega, Concepcion Civera-Tejuca, Luis Callol-Sanchez
Journal: European Respiratory Journal (2013)

Tobacco smoke exposure is the main risk factor for the development of LC and COPD. In turn, COPD is a risk factor for the development of LC. Tobacco smoke contains a large number of free radicals, reactive oxygen species and reactive nitrogen species that increase oxidative stress. Damage to membrane lipids (lipid peroxidation) produces different VOC (aldehydes, carboxylic acids, etc.) that can be detected in exhaled breath.

OBJETIVE: To determine whether there are differences between exhaled VOC in lung cancer patients with and without COPD.

METHODS: Case-control study. 81 patients with LC (57 with COPD and 24without COPD). Informed consent accepted. Chemical analysis: Thermal Desorption/ Gas Chromatography-Mass Spectrometry (Markes-Agilent Tech).Statistical analysis: SPSS®v-15 for Windows.

RESULTS : Description of the sample. Quantitative and qualitative study of VOC.

![Figure][1] 



We observed statistically significant low concentrations of propanoic acid in lung cancer patients without COPD in comparison to those with COPD.

CONCLUSSIONS: 

1. 70% of LC patients have associated to COPD.

2. Propanoic acid shows statistical significance difference.

3. Indeed, the probability to find propanoic acid in LC with COPD patients isn't high: this VOC was not exhaled in 85% of LC without COPD patients.

Supported by FIS: PI07/1116; Neumomadrid 2008, SEPAR 2009/881; Neumomadrid 2012.

 [1]: pending:yes
Bloodstream infections as a marker of community-acquired sepsis severity. Results from the Portuguese community-acquired sepsis study (SACiUCI study)
Authors: J. Gonçalves-Pereira, P.R. Povoa, C. Lobo, A.H. Carneiro
Journal: Clinical Microbiology and Infection (2012)

The impact of bloodstream infection (BSI) on admission to hospital on the outcome of patients with community-acquired sepsis (CAS) admitted to intensive-care units (ICU) is largely unknown. We selected 803 adult patients consecutively admitted with CAS to one of 17 Portuguese ICU, in whom blood cultures were collected before initiation of antibiotic therapy during a 12-month period. A BSI was identified on hospital admission in 160 (19.9%) patients. Those with and without BSI had similar mean Simplified Acute Physiology Score (SAPS) II and age. The presence of BSI was independently associated with mortality in ICU (adjusted odds ratio 1.86; 95% confidence interval 1.20-2.89; p 0.005). On the 4th day in ICU, patients with BSI were found to be significantly more dependent on vasopressor support (p 0.002) but not on ventilatory support. Cumulative ICU mortality was significantly higher in BSI patients from the 9th day onwards. A seasonal variation of BSI isolates was noted: gram-negative BSI were more common in the summer, whereas in the winter, gram-positive infections were more frequent (p 0.024), without mortality differences.
Protective effects of glutathione, glycine, or alanine in an in vitro model of renal anoxia.
Authors: M S Paller, M Patten
Journal: Journal of the American Society of Nephrology (1992)

Both glutathione and glycine provide some protection against ischemic renal injury in a variety of experimental models. However, results have been inconsistent and there may also be model heterogeneity. The effects of glutathione, glycine, and alanine in a cell culture model of renal anoxia/reoxygenation injury were tested. When primary cultures of rat proximal tubule epithelial cells were subjected to 60 min of anoxia and 30 min of reoxygenation, glutathione (2 mM) essentially eliminated lethal cell injury as determined by lactate dehydrogenase release. Glycine or alanine, on the other hand, provided only partial protection. Glutamate did not protect, although cysteine did. The glutathione synthesis inhibitor buthionine sulfoximine blocked the protective effect of exogenous glutathione, and the glutathione transport inhibitor probenecid partially blocked glutathione protection. A combination of glycine, glutamate, plus cysteine also protected against anoxia/reoxygenation injury. The studies suggest that both glutathione degradation with intracellular resynthesis and transport of intact glutathione into the cell are involved in the protection afforded by exogenous glutathione. These results are different from those obtained in other experimental models of renal ischemia, such as freshly isolated proximal tubules, because the protective effects of glutathione were not derived solely from glycine generation. These studies also suggest the need for caution in extrapolating results from one model of renal anoxic injury to another.
Impact of prompt catheter withdrawal and adequate antimicrobial therapy on the prognosis of hospital-acquired parenteral nutrition catheter-related bacteraemia
Authors: D. Rodríguez-Pardo, B. Almirante, N. Fernández-Hidalgo, C. Pigrau, C. Ferrer, A.M. Planes, R. Alcaraz, R. Burgos, A. Pahissa
Journal: Clinical Microbiology and Infection (2014)
The 'Sleep-Disordered Breathing in Patients with Neuromuscular Disease' questionnaire (SiNQ-5) - Clinical usefulness in a tertiary referral centre
Authors: Michelle Ramsay, Panagis Drakatos, Martino Pengo, Chris Kosky, Craig Davidson, Nicholas Hart, Joerg Steier
Journal: European Respiratory Journal (2012)

Introduction: Patients with neuromuscular disease (NMD) are at risk of developing sleep-disordered breathing (SDB) with hypercapnic respiratory failure. We hypothesised that the SiNQ-5 score may be useful to assess patient who are ventilated for NMD with SDB.

Methods: We screened patients attending a tertiary referral centre for investigation of SDB, administering the SiNQ-5 (range 0-10 points, lower scores indicating fewer symptoms). The questionnaire contains five questions related to breathlessness, sleep and posture (Steier et al, Eur Respir J, 2011). 236 (105 female) patients had complete data sets. Treatment was defined as either continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV). Results were compared using the Mann-Whitney U independent t-test . 

Results: 141 patients had obstructive sleep apnoea and obesity hypoventilation syndrome (score 4.1(2.7)), 51 had NMD (3.5(2.8)), 16 had chronic obstructive pulmonary disease (COPD, 4.3(2.6)) and 6 had chronic heart failure (CHF, 5.7(2.8)), 52 patients had no evidence of SDB (4.4(2.7)). 28 patients had NMD with SDB; 26 of those were treated for SDB with a total score of 2.9 (2.5) points, 2 were untreated, scoring 4.0 (0.0) points. Patients with NMD without SDB did not differ from those with SDB who were controlled on treatment (p=0.3) or from Snorers without SDB (p=0.53).

Conclusion: NMD patients with controlled SDB are likely to score similarly to those without SDB and lower than other groups. In order to further address its clinical usefulness it is necessary to follow up and correlate clinical outcomes to the SiNQ-5 scores changes associated with treatment.
Difficulties experienced by the asthmatic patients in southern Turkey
Authors: Hicran A. Bektas, Ilkay K. Keser, Arzu O. Akcan
Journal: European Respiratory Journal (2012)

Chronic diseases like asthma have a great impact on the everyday life of patients. The purpose of this descriptive study was to determine the difficulties experienced by the asthmatic patients in Southern Turkey. The sample was composed of 105 asthma patients who had been receiving medical therapy in Akdeniz University Hospital. Data were collected through a demographic data form and the questionnaire about the asthma patients' physical, psychological, social, economic and treatment-related difficulties. The asthma patients in the sample averaged 55.68 years of age (SD 12.29 years, range 18–85) and included most patients who were female (61.9%), married (77.1%), housewife (47.6%) and had completed primary education (40%). Difficulties experienced by the asthmatic patients physically were dyspnea (85.7%), wheezing (82.9%), tiredness (82.9%), cough (76.2%), psychologically were sadness (85.7%), anxiety (64.8%), anger (59.0%), panic (45.7%), socially were do not enter to the closed /crowded places (65.7%), do not go to see to their relatives / friends, economically were loss of income (36.2%), inability to pay for expensive drug charges (30.5%), inability to pay the hospital fees (14.2%), inability to pay fees for the treatment (12.4%), treatment-related difficulties were not having an adequate knowledge about the asthma attack (48.5%), not receiving an adequate information about the treatment (32.3%), not being aware of the consequences of the treatment (23.8%). The information gathered from this study led us to reevaluate the healthcare services for asthmatic patients to improve physical, psychological, and social aspects of the nursing care as a whole.
The effects of inspiratory muscle training on respiratory muscle strength and pulmonary functions in children with bronchiectasis
Authors: Hulya Nilgun Gurses, Burcu Ayhan, Rengin Demir, Semiramis Ozyilmaz
Journal: European Respiratory Journal (2013)

Aim:  The aim of this study was to examine the effects of inspiratory muscle training on respiratory muscle strength and pulmonary functions in children with bronchiectasis   Methods:  A randomized, double-blind, prospective study was carried out by comparing two groups of children with stable bronchiectasis. Group A was trained with inspiratory-threshold loading device and cough training. Group B received a single cough teaching session. 16 children were in Group A (mean age:11,81±2,71 years) and 15 children were in Group B (mean age:12,07 ±2,25 years). Patients in Group A trained at inspiratory-threshold loads up to 40% of maximal static inspiratory pressure (PImax) and patients in Group B did not participate in any form of training. Pulmonary functions (VC, FRC, FEV1, PEF, MEF%50, MVV, MMF) and respiratory muscle strength measurements (PImax and PEmax) were performed at the beginning and at the end of the study. For statistical analyses; independent sample t-test, Mann Whitney U test, Wilcoxon Signed-rank test and paired t-test were used.   Results:  Demographic findings were similar (p>0, 05) in two groups. There were significant improvements in pulmonary functions and respiratory muscle strength measurements (p≤0, 05) in Group A patients, while no significant difference was seen in Group B patients after eight weeks.   Conclusion:  From these results, we concluded that inspiratory muscle training improves respiratory muscle strength and pulmonary functions in children with bronchiectasis. It is also observed that cough training helped children to expectorate easily.  Funding: Istanbul University Research Foundation.
Does Wells score documentation really prevent excessive CTPA requests in a teaching hospital? A retrospective study in 800 patients
Authors: Pradeep Rajagopalan, James Wingfield Digby, Ciara Lee, R.D. Barker
Journal: European Respiratory Journal (2014)

Introduction: CTPA is the recommended diagnostic modality for pulmonary embolism and the Well9s score is a well-known measure of pre-test probability. We undertook a retrospective audit to examine the correlation between Wells score > 4 and CTPA positivity.  Methods: We obtained all CTPA requests undertaken in a teaching hospital between January and August 2013. Our hospital CTPA requests are made electronically requiring clinical details, Wells score and D-Dimer. If the Wells score is > 4 then a PE is considered likely and D-dimer is not required. Excluding duplicate requests or cancelled scans left a total of 800 requests. Of these, 747 CTPAs and 53 V/Q scans were performed (data excluded). Of these 747 CTPAs we had data from the initial request forms including Wells score and D-dimer for 693 of these patients.  Results: 747 CTPAs were performed during the study period. Of those, 1% (7) were equivocal, 83% (619) negative and 16% (121) positive. Of the positive CTPA scans 13 were excluded as request form details were not recorded leaving a total of 108. 72% (78) of these patients had a Well9s score of > 4, 28% (30) had a Wells score of   4. 22% (126) had a Wells score of   Conclusion: Despite having an online requesting system which takes a high pre-test probability (Wells>4) into account, excessive CTPA requests were made. This presents an interesting finding and we plan to re-audit after conducting training sessions on the use of the Wells score.
Treatment of leukemia antigen-loss relapses occurring after CD19-targeted immunotherapies by combination of anti-CD123 and anti-CD19 chimeric antigen receptor T cells
Authors: Marco Ruella, David M Barrett, Saad S Kenderian, Olga Shestova, Ted J Hofmann, John Scholler, Simon F Lacey, Jan J Melenhorst, Farzana Nazimuddin, Jessica Perazzelli, David A Christian, Christopher A Hunter, David L Porter, Carl H June, Stephan A Grupp, Saar Gill
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Anti-CD19 chimeric antigen receptor T cells (CART19) and bi-specific anti-CD19/CD3 antibodies (blinatumomab) are generating unprecedented complete responses in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, a subset of patients still relapse and