tbuckley/cabot-search huggingface dataset:
Abstract 1688: Integrative sequencing discovers a novel <i>PGAP3-SRPK1</i> gene fusion in sinonasal undifferentiated carcinoma
Authors: Erin L. McKean, Andrew C. Birkeland, Molly E. Heft Neal, Aditi Kulkarni, Sue K. Foltin, Brittany M. Jewell, Jonathon B. McHugh, Lawence J. Marentette, John Chad Brenner
Journal: Cancer Research (2019)

Abstract Sinonasal Undifferentiated Carcinoma (SNUC), a rare and aggressive tumor arising from the sinonasal cavity, remains a difficult-to-treat disease with poor overall survival. There are no agreed upon treatment algorithms and research efforts have focused on identifying new genetic mutations for novel targeted therapies. To date, targeted sequencing studies have identified IDH2 and SMARCAB1 as potential SNUC driver alterations, however the molecular alterations found in SMARCAB1 wild type tumors are unknown. Here, using whole exome sequencing, we characterize a series of 7 SNUC tumors and a SNUC cell line and discover recurrent aberrations to the SWI/SNF, MAGE and FAT gene families. We also validate a novel ALK mutation, recurrent ERBB2 copy number amplifications and a previously undescribed PGAP3-SRPK1 gene fusion in the SNUC cell line. Further investigation of the PGAP-SRPK1 fusion gene reveals a change in the active site with loss of three of nine active site residues. Functional studies are ongoing to determine the importance of the PGAP3-SRPK1 gene fusion for oncogenic phenotypes. This discovery extends the need for comprehensive characterization of gene family mutation status in SNUC and supports a need to understand the downstream molecular mechanisms in order to improve therapeutic strategies for this disease. Citation Format: Erin L. McKean, Andrew C. Birkeland, Molly E. Heft Neal, Aditi Kulkarni, Sue K. Foltin, Brittany M. Jewell, Jonathon B. McHugh, Lawence J. Marentette, John Chad Brenner. Integrative sequencing discovers a novel PGAP3-SRPK1 gene fusion in sinonasal undifferentiated carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1688.
From the Health Care Financing Administration
Authors: B. C. Vladeck
Journal: JAMA (1994)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Current status of patient education
Authors: D. D. Etzwiler
Journal: JAMA (1972)

Today we are experiencing rapid changes in the health care field. The primary reasons for these alterations are a rapid accumulation of new knowledge, advancing technology, and an overwhelming demand for health care. Within this revolution, there is also a change in the prevalence of diseases and in the methods of treatment. At the turn of the century, acute infectious diseases were the leading cause of death in the United States. By 1970, only one infectious disease ranked among the top ten killers. Thus, the kind of medical care most needed is being shifted away from the treatment of acute disease and crisis situations and diverted to health maintenance and the control of chronic disease. Unfortunately, most physicians have been attracted to and primarily trained in the management of acute conditions. Such care does provide stimulation and excitement; a feeling of immediate satisfaction and fulfillment and also considerable financial compensation.
Fresh vs Preserved Stool Specimens for Detection of Parasites
Journal: JAMA (1996)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Caucasus as an Asymmetric Semipermeable Barrier to Ancient Human Migrations
Authors: B. Yunusbayev, M. Metspalu, M. Jarve, I. Kutuev, S. Rootsi, E. Metspalu, D. M. Behar, K. Varendi, H. Sahakyan, R. Khusainova, L. Yepiskoposyan, E. K. Khusnutdinova, P. A. Underhill, T. Kivisild, R. Villems
Journal: Molecular Biology and Evolution (2012)
The Perception of Dyspnea
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
THE DISCUSSIOM OF CHOLERA AT THE WIESBADEN CONGRESS FOR INTERNAL MEDICINE, APRIL 12-15, 1893.
Journal: JAMA (1893)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Liberal Benefits, Conservative Spending
Authors: Kevin Grumbach, Thomas Bodenheimer, David U. Himmelstein, Steffie Woolhandler
Journal: JAMA (1991)

The Physicians for a National Health Program proposes to cover all Americans under a single, comprehensive public insurance program without copayments or deductibles and with free choice of provider. Such a national health program could reap tens of billions of dollars in administrative savings in the initial years, enough to fund generous increases in health care services not only for the uninsured, but for the underinsured as well. We delineate a transitional national health program budget that would hold overall health spending at current levels while accommodating increases in hospital and physician utilization. Future national health program spending would be indexed to the growth in gross national product adjusted for demographic, epidemiologic, and technologic shifts. Financing for the national health program would transfer funds into the public program without disrupting the general pattern of current revenue sources. We suggest a funding package that would augment existing government health spending with earmarked health care taxes. Because these new taxes would replace employer-employee insurance premiums and substantial portions of current out-of-pocket expenditures, they would not increase health costs for the average American. (<i>JAMA</i>. 1991;265:2549-2554)
PD-L1 and CD8 expression and association with outcomes in patients (pts) with <i>BRAF</i> V600E/K-mutant metastatic melanoma (MM) who received dabrafenib + trametinib (D+T) in the randomized phase 3 COMBI-v study.
Authors: Dirk Schadendorf, Georgina V. Long, Jean Jacques Grob, Paul D. Nathan, Antoni Ribas, Michael A. Davies, Keith T. Flaherty, Matthew Squires, Savina Jaeger, William Powell, Puay Tan, Caroline Robert
Journal: Journal of Clinical Oncology (2017)

9527 Background: The phase 3 COMBI-v study (NCT01597908) showed that D+T significantly improved outcomes vs vemurafenib in pts with BRAFV600E/K–mutant MM. Checkpoint inhibitors also provide clinical benefit in some pts with MM. To date, characterization of markers associated with response to anti–PD-1 therapy has identified positive associations with PD-L1 expression and immune cell infiltration. Here we describe expression of PD-L1 and the T-cell marker CD8 in tumor samples from pts randomized to receive D+T in COMBI-v and associations with clinical outcomes. Methods: Biopsies from 74 of 352 D+T pts (21%) in COMBI-v were assessed for expression of PD-L1 (PD-L1 IHC 22C3 pharmDx assay; Dako) and CD8 (anti-CD8 antibody, clone C8/144B; Dako). PD-L1 positivity was determined as a percentage of stained tumor cells and MEL score (staining on both tumor and mononuclear inflammatory cells; 0 or 1 [negative]: &lt; 1% staining; 2-5 [positive]: ≥ 1% staining; Daud et al. J Clin Oncol. 2016). Results: Of 74 pts analyzed, 54 (73%) had PD-L1–positive tumors, and the largest MEL score subgroup was 2 (45%). A significant association ( P &lt; .0001) was observed between PD-L1 and CD8 expression. Overall response rate, tumor shrinkage, progression-free survival, overall survival (OS), and duration of response with D+T were not associated with PD-L1 (MEL score of ≥ 2) or CD8 positivity. However, a significant association ( P = .04) with improved OS was observed in tumors with high PD-L1 expression (≥ 20% of cells PD-L1 positive), and a trend ( P = .06) was seen in pts with a MEL score of ≥ 3. Among PD-L1–negative pts, improved OS was seen in those with high CD8 positivity ( P = .03), particularly in the stromal compartment. Conclusions: These data, representing PD-L1 and CD8 expression profiles for a BRAF-mutant mm population in the context of outcomes following D+T, showed that clinical benefit was maintained regardless of immune phenotype. The results also suggest that an immune component has an impact on outcomes following targeted therapy. Clinical trial information: NCT01597908.
The aging thyroid
Authors: S. Mariotti
Journal: Endocrine Reviews (1995)

THE number and proportion of elderly people are steadily growing in western societies as a consequence of increased life expectancy and reduced birth rate. This phenomenon has important social, economical, and public health implications and has generated a number of studies aimed at clarifying the basis of the physiological and pathological aspects of aging. In this context, endocrine function in the elderly has been the object of particular attention (1–9). An important concept derived from these studies is that while the equilibrium concentrations of the principal hormones are substantially normal in most healthy elderly, with advancing age there are significant alterations in hormone production, metabolism, and action, with consequent achievement of new equilibria. As proposed by Mooradian et al. (4), aging may be defined as a time of reduced adaptability to metabolic perturbation. It has been repeatedly suggested that some of these changes may play a role in the pathophysiology of senescence, but the evidence for this is still very limited. The thyroid gland plays an important and specific role in the relationships between the endocrine system and aging (10–22). First, it is well recognized that symptoms of aging can easily be confused with hypothyroidism, and in the past decreased thyroid function was believed to be one of the hallmarks of the aging process (14,16). Second, thyroid diseases are common in the elderly, but their clinical manifestations are frequently different from those seen in younger patients; they are more subtle and often hidden by a background of intercurrent disease.
Gene therapy and the hemophilias
Authors: J. N. Lozier
Journal: JAMA (1994)

Gene therapy for hemophilia A and B, now in the developmental stage, holds promise of a therapeutic revolution, resulting in amelioration or cure of the hemorrhagic diatheses. The genes for factor VIII and IX have been cloned, and vectors for the transfer of their cDNA into cells have been developed. Although viral and nonviral constructs containing the hemophilia gene have been used, most often modified retroviruses or adenoviruses have been employed. Cells that have been targeted for genetic modification to produce the antihemophilic proteins include hepatocytes, muscle cells, endothelial cells, keratinocytes, and fibroblasts. The delivery system may be (1) ex vivo, with implantation of modified cultured hemophilic cells in the donor, either in tissues or in semipermeable capsules, or (2) in vivo, the vector being delivered directly to target cells, genetically modifying them in situ. Successful in vivo therapy has been demonstrated in a hemophilic animal model, with conversion to a less severe hemophilic state. (<i>JAMA</i>. 1994;271:47-51)
Gastric Flora in Chronically Mechanically Ventilated Patients: Relationship to Upper and Lower Airway Colonization
Authors: Lucy B. Palmer, Susan V. Donelan, Gail Fox, Enes Bellemore, William H. Greene
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The oropharynx, stomach, and trachea are all potential reservoirs for gram-negative organisms in mechanically ventilated patients. The pathogenic importance of each site in respiratory infection may differ between mechanically ventilated patients who are medically stable and the critically ill, and these differences may be important in understanding the pathogenesis of nosocomial infection. We prospectively studied seven patients requiring chronic ventilatory assistance who were otherwise medically stable to determine the pattern of gram-negative colonization of these three sites. Serial weekly oropharyngeal, gastric, and tracheal cultures were taken over a 6-mo period in our Respiratory Care Unit for chronically ventilator-dependent patients. Pseudomonas aeruginosa (PA) was present more frequently and persistently in the trachea than the oropharynx and stomach (p < 0.01) and members of the family Enterobacteriaceae (Ent. species) were also observed more commonly in the trachea than the oropharynx (p < 0.01). PA was seen in 6.7% of gastric specimens whereas Ent. species were found in 40% of gastric specimens. Six identical strains from a total of 53 gastric isolates and 128 oropharyngeal isolates were cultured coincidentally from these two sites. Coincidental isolation of 11 strains was observed in 177 tracheal isolates and 53 gastric samples. Documented transfers from stomach to oropharynx ascertained by sequential isolation occurred in one of 118 cultures and transfer from stomach to trachea occurred in three of 134 cultures. In summary, the stomach does not appear to be an important reservoir for gram-negative colonization in chronically mechanically ventilated patients. Despite the use of H2 blockers in six of seven patients, transfer of organisms rarely occurred from the stomach to the oropharynx or trachea. The trachea had the most frequent and persistent colonization with gram-negative organisms.
A NEW OCCUPATION DISEASE.
Journal: JAMA (1905)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Tai Y-T, Soydan E, Song W, Fulciniti M, Kim K, Hong F, Li X-F, Burger P, Rumizen MJ, Nahar S, Podar K, Hideshima T, Munshi NC, Tonon G, Carrasco RD, Afar DEH, Anderson KC. CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf–mediated interactions with bone marrow stromal cells. Blood. 2009;113(18):4309–4318.
Journal: Blood (2010)
Bastard Dosage
Authors: S. K. Sen
Journal: BMJ (1960)

<h3>Abstract</h3> Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients, occurring even more frequently in cases with anti-epileptic drug resistance. However, the underlying mechanism of SUDEP remains elusive. Our previous study demonstrated that enhancement of serotonin (5-HT) synthesis by intraperitoneal (IP) injection of 5-hydroxytryptophan (5-HTP) significantly reduced the incidence of seizure-induced respiratory arrest (S-IRA) in a DBA/1 mouse SUDEP model. Given that the 5-HT2A receptor (5-HT2AR) plays an important role in mediating the respiration system in the brain, we hypothesized that 5-HT2AR plays a key role in S-IRA and SUDEP. To test this hypothesis, we examined whether the decreased incidence of S-IRA evoked by either acoustic stimulation or pentylenetetrazole (PTZ) injection following 5-HTP administration will be blocked by treatment with ketanserin (KET), a selective antagonist of 5HT2AR, in the DBA/1 mouse SUDEP model. We observed that the reduction in S-IRA by 5-HTP was significantly reversed by IP or intracerebroventricular injection of KET. Considering the localization of 5-HT2AR in the pre-Bötzinger complex (PBC), which plays a key role in regulating respiratory rhythm, we next examined whether KET acts on 5-HT2AR in the PBC. To test this hypothesis, we activated the neural circuit between the dorsal raphe nucleus (DR) and PBC using optogenetics technology. We observed that stimulation of TPH2-ChETA-expressing neurons in the DR reduced the incidence of S-IRA evoked by PTZ, and this suppressant effect was significantly reversed by administration of KET in the bilateral PBC with no changes in electroencephalogram activity. The neural circuit between the DR and PBC was confirmed by injection of cholera toxin subunit B555 (CTB-555), a nerve tracer, in the DR or PBC separately. Calcium signaling evoked by PTZ within neurons of the PBC during seizures was significantly reduced by photostimulation of the DR. Taken together, our findings suggest that 5-HT2AR plays a critical role in regulating S-IRA and targeting the serotonergic neural circuit between the DR and PBC is a promising approach to preventing SUDEP.
Non-invasive monitoring of liver disease regression in patients with advanced chronic liver disease after sustained virologic response to INF-free therapies
Authors: Georg Semmler, Teresa Binter, Karin Kozbial, Philipp Schwabl, David Chromy, David J.M. Bauer, Benedikt Simbrunner, Bernhard Scheiner, Theresa Bucsics, Albert Stättermayer, Matthias Pinter, Petra Munda, Michael Trauner, Peter Ferenci, Thomas Reiberger, Mattias Mandorfer
Journal: Journal of Hepatology (2020)
Ruptured arteriosclerotic aneurysms of the abdominal aorta. Reducing mortality
Authors: L. W. Ottinger
Journal: JAMA (1975)

Mortality in 100 patients undergoing resection of ruptured atherosclerotic aneurysms of the abdominal aorta was 58%. In addition to advanced age and concurrent cardiac disease, lethal factors included preoperative hypotension, cardiac arrest, anuria, and free intra-abdominal rupture. Failure to establish the correct diagnosis until the onset of these four signs contributed to the high mortality. (<i>JAMA</i>233:147-150, 1975)
GRADE approach to drawing conclusions from a network meta-analysis using a partially contextualised framework
Authors: Romina Brignardello-Petersen, Ariel Izcovich, Bram Rochwerg, Ivan D Florez, Glen Hazlewood, Waleed Alhazanni, Juan Yepes-Nuñez, Nancy Santesso, Gordon H Guyatt, Holger J Schünemann
Journal: BMJ (2020)

This article describes GRADE (grading of recommendations assessment, development and evaluation) guidance on how to make conclusions from a network meta-analysis of interventions that includes individual randomised controlled trials for one outcome at a time. The guidance is based on a partially contextualised approach in which review authors must establish ranges of magnitudes of effect that represent a trivial to no effect, small but important effect, moderate effect, and large effect. The principles guiding this framework are that interventions should be grouped in categories, based on the magnitude of the effect; and that the judgments that place interventions in such categories should consider the estimates of effect, the certainty of the evidence, and the rankings. We describe and illustrate the four steps of this framework using an example.