tbuckley/cabot-search huggingface dataset:
Molecular characterization of neuroendocrine prostate cancer (NEPC) and identification of new drug targets.
Authors: H. Beltran, D. Rickman, K. Park, A. Sboner, T. Macdonald, S. T. Tagawa, M. B. Gerstein, F. Demichelis, D. M. Nanus, M. A. Rubin
Journal: Journal of Clinical Oncology (2011)

4536 Background: NEPC is an aggressive variant of prostate cancer that can arise de novo or from existing prostate adenocarcinoma (PCA), and is promoted by the use of hormonal therapy. We sought to better understand the molecular transformation of NEPC and identify new drug targets. Methods: Using Next Generation RNA sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate (BEN), and validated findings on tumors from a large cohort of patients (30 NEPC, 118 PCA, 30 BEN) using IHC and FISH. Functional studies were performed using NCI-H660 (NEPC), VCaP and LNCaP (PCA), RWPE (BEN). Results: ERG rearrangement was present in 47% of NEPC, but ERG protein expression was absent and corresponded with lack of AR. There were significant molecular differences between NEPC and PCA, with 936/25932 genes differentially expressed (P<0.001). Aurora kinase A (AURKA) and N-myc (MYCN) were overexpressed in NEPC vs PCA (P<0.001), and both genes were amplified in 35% of NEPC, 5% of PCA, and none of BEN. Transfection of MYCN induced AURKA expression and kinase activity in vitro, and AURKA induced MYCN. Either MYCN or AURKA induced expression of neuroendocrine markers (SYP, NSE) in RWPE and LNCaP, and N-myc directly binds promoters of NSE, SYP, and AR to regulate their expression (and downstream androgen regulated genes). After validating NCI-H660 as model of NEPC, we observed enhanced in vitro and in vivo sensitivity to the Aurora kinase inhibitor PHA-739358 compared to LNCaP and VCaP, with > 50% tumor shrinkage in NEPC and minimal to no effect in PCA. Phospho-H3, a downstream marker of Aurora kinase activity, was inhibited in the treated NCI-H660 and not in PCA. Notably, NE marker expression was suppressed in the treated NCI-H660 xenografts, again supporting a role of Aurora kinase in modulating the NE phenotype. Conclusions: There is likely clonal origin of NEPC from PCA (with ERG fusion in both), but ERG expression limited to PCA and driven by AR signaling. We discovered significant overexpression and amplification of AURKA and MYCN in NEPC and a small subset of PCA, and evidence that that they cooperate and induce a NE phenotype in prostate cells. In vitro and in vivo data confirms that these are novel drug targets for NEPC.
TYPHOID FEVER IN CHILDREN.
Journal: JAMA (1901)

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
Abstract 21410: Utility of Ratio of Maximum Leaflet Thickness to Residual Radius in Predicting Aortic Root Rupture or Hematoma During Transcatheter Aortic Valve Replacement
Authors: Yujun Sun, Alexis Okoh, Isheeka Edwards, Sunil Kanwal, Mark Russo, Marc . Cohen, Bruce Haik, Chunguang Chen
Journal: Circulation (2017)

Introduction: Aortic root rupture or hematoma (ARR or ARH) is a serious complication of transcatheter aortic valve replacement (TAVR). In addition to excessive oversizing (annular area/TAVR stent area) and aortic annular calcification. Hypothesis: We hypothesize that combination of small sinus of Valsalva (SOV) and excessive calcification of aortic leaflets is a significant risk factor for ARR or ARH. Methods: Patients who experienced ARR or ARH during TAVR were selected. A matched cohort who had no complications during the procedure were identified from a prospectively maintained database. Dynamic 4-D cardiac computed tomography was used to assess respective thickness of the three aortic cusps, SOV, annular area, LVOT, and the presence and extent of calcification of the LVOT. The ratio of maximum leaflet thickness (MLT) to residual radius (RR): (SOV diameter - TAVR stent diameter)/2), and TAVR stent oversizing: (TAVR stent area - aortic annular area)/TAVR stent area were calculated and severity of annular calcification graded. Stepwise logistic regression using backward selection was used to determine factors associated with ARR or ARH during TAVR. Results: Out of 800 TAVR patients, ARR/ARH occurred in 18 (2.2%) during the procedure. There were 19 well-matched (no complication) patients who served as a control group. Baseline clinical characteristics were similar in ARR/ARH - patients and ARR/ARH + patients. LVOT calcification was ≥ moderate in 61 % of ARR+ patients and 31 % in ARR- patients. The overall incidence of bio prosthetic valve oversizing 37% (n=14). On multivariable logistic regression analysis, an MLT/RR ratio &gt; 1.4, prosthetic valve oversizing ≥ 20% and ≥ moderate or greater annular calcification were significantly associated with ARR during TAVR. Conclusions: In addition to excessive oversizing of &gt;20% and annular calcification, a high MLT/RR ratio, a parameter for a combination of small sinus of Valsalva and excessive leaflet calcification, is an independent predictor of ARR or ARH.
Unbuckling lipodystrophy from insulin resistance and hypertension
Authors: Robert A. Hegele, Todd Leff
Journal: Journal of Clinical Investigation (2004)

Lipodystrophy and insulin resistance are the core features of human PPARγ deficiency states. Metabolic complications in PPARγ deficiency, such as hypertension, have been considered to be secondary to insulin resistance. However, a new mouse model that expresses the analog of a human PPARG mutation displays minimal lipodystrophy and insulin resistance but rather severe hypertension. Furthermore, the mutant protein appears to directly modulate the renin-angiotensin system in adipose tissue, providing evidence of the pleiotropic effects of PPARγ.
Unemployment among hospital junior staff: BMA inquiry
Journal: BMJ (1983)

Unemployment among -hospital junior staffAs part of its evidence to the review body the BMA submitted a report of an inquiry con- ducted by its permanent committee on manpower into the pattern of employment of hospital junior staff.This inquiry, which has now been published, took the form of a postal survey of a random sample of 2000 junior hospital doctors, from which 896 (45%) usable responses were obtained.The key re- sults are summarised here.* Thirty five (4%) of the respondents were unemployed on the chosen date of 1 June 1982.* Sixty four per cent of respondents had suffered no period of unemployment since registration; 19% had suffered one such period and 15% between two and five.* Of those who had been unemployed at any stage, 15% had been unemployed for a period over three months but the most common periods of unemployment were up to one month (20%) and one to two months (21%).
Ambulatory dialysis: special boon for children
Authors: E. Blume
Journal: JAMA (1983)

Continuous ambulatory peritoneal dialysis (CAPD) is helping young patients with kidney disease lead more normal lives, says Richard N. Fine, MD, head of the Division of Pediatric Nephrology at the UCLA Center for Health Sciences. Fine discussed the technique's pediatric use at a recent National Kidney Foundation meeting in Washington, DC. About 700 children develop end-stage renal disease (ESRD) in the United States each year. Although Fine considers the optimal treatment for such youngsters to be a successful kidney transplant, a period of dialysis, sometimes quite lengthy, is usually needed until a donor organ becomes available or in the case of graft rejection (<i>JAMA</i>[MEDICAL NEWS] 1983;249:1416). In the past, children needing dialysis have usually received intermittent hemodialysis at medical centers. With this form of treatment, Fine noted, the necessary fluid and dietary restrictions may be onerous, as may the repeated needle punctures. Rehabilitation is limited by the considerable time
Typhoid Carriers and Typhoid Immunity. Omnis Typhus ex Typho.
Journal: JAMA (1922)

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
CHAIRMAN'S ADDRESS.
Authors: G. V. I. BROWN
Journal: JAMA (1898)

It is my pleasure, as your chairman, to give the first greeting to the Section of Stomatology of this Association, and also to our confrères in joint session, the Colorado dentists, among whom I trust it may be the inaugural of long and beneficial intercourse. Stomatologists in fact we have long been, I am sure, but to be so recognized by title is a long step forward in the direction toward which, from year to year, those who have carried the burden of the vast amount of work necessary to this Section have labored, and is certainly worthy of general congratulation. We no longer serve under the somewhat limited, almost ambiguous term of "oral surgeons," but are hereafter to be recognized as those having understanding of the science of the mouth, a tribute complimentary to the scientific character of papers which, published side by side in the journal of this
Omission of Additional Contributions
Authors: Preeti Mehrotra, Andi Shane, Aaron Milstone
Journal: JAMA Pediatrics (2016)

Yung-Sen Chang, MD, MPH; Michelle K. Trivedi, MD, MPH; Ayan Jha, MBBS, MPH; Yen-Feng Lin, MD; Liezeel Dimaano, MD, MPH; Maria T. García-Romero, MD, MPH
Visual Processing In Monkey Extrastriate Cortex
Authors: J. Maunsell
Journal: Annual Review of Neuroscience (1987)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Effect of hypnotic suggestion on the delayed-type hypersensitivity response
Authors: S. E. Locke
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. <h3>Design.</h3> —A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. <h3>Setting.</h3> —A National Institutes of Health—supported clinical research center in a teaching hospital. <h3>Subjects.</h3> —A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean±SD age of 22±6 years. The mean±SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11±1. <h3>Interventions.</h3> —Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. <h3>Main Outcome Measures.</h3> —Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. <h3>Results.</h3> —The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. <h3>Conclusions.</h3> —Our subjects were unable to alter their DTH responses using hypnotic suggestion. (<i>JAMA</i>. 1994;272:47-52)
Solid Wastes from Nuclear Power Production
Authors: Harvey F. Soule
Journal: Environmental Health Perspectives (1978)

Radioactivity in nuclear power effluents is negligible compared to that in retained wastes to be disposed of as solids. Two basic waste categories are those for which shallow disposal is accepted and those for which more extreme isolation is desired. The latter includes "high level" wastes and others contaminated with radionuclides with the unusual combined properties of long radioactive half-life and high specific radiotoxicity. The favored method for extreme isolation is emplacement in a deep stable geologic formation. Necessary technologies for waste treatment and disposal are considered available. The present program to implement these technologies is discussed, including the waste management significance of current policy on spent nuclear fuel reprocessing. Recent difficulties with shallow disposal of waste are summarized.
The effect of Verapamil containing cold flush solution on the outcome of transplanted livers Dale Distant; John Wallace; Lars Backman; Caren Eisenstein; Tom Renard; Marlon Levy; Robert Goldstein; Bo Husberg; Thomas Gonwa; Goran Klintmalm. Baylor University Medical Center, Transplantation Services, 3500 Gaston Avenue, Dallas, TX 75246
Journal: Hepatology (1993)
Commentaire du travail de Britto-Arias M et al., pp. 898
Authors: Gilles Lesur
Journal: Endoscopy (2015)

See also: Forceps versus snare polypectomies in colorectal cancer screening: are we adhering to the guidelines?Endoscopy 2015; 47(10): 898-902DOI: 10.1055/s-0034-1392328
Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer
Authors: T. A. DiPetrillo, V. Pricolo, W. M. Sikov, J. Lagares-Garcia, M. Vrees, N. Oldenburg, H. Khurshid, B. McNulty, J. Shipley, H. Safran
Journal: Journal of Clinical Oncology (2008)

15041 Background: This study was designed to assess whether a short course of induction therapy with bevacizumab (B) and FOLFOX chemotherapy followed by concurrent B and preoperative chemoradiation (chemoXRT) with weekly oxaliplatin (OX) and continuous infusion (CI) 5-fluorouracil (5-FU) would increase the pathologic complete response (pCR) rate at surgery in patients (pts) with stage II-III rectal cancer. Methods: Pts received 2 biweekly courses of B 5 mg/kg and modified FOLFOX6 followed by B 5 mg/kg q2wks, OX 50 mg/m2 weekly (subsequently reduced to 40 mg/m2/week due to an unacceptably high incidence of grade 3 diarrhea), and CI 5-FU 200 mg/m2/day concurrent with 50.4 Gy pelvic radiation over 6 weeks. Surgical resection was performed between 4 and 8 weeks after completion of preoperative chemoXRT. Adjuvant chemotherapy, consisting of 6 biweekly course of B/modified FOLFOX6, was initiated 4–12 weeks after surgery. Results: Twenty-three pts have been enrolled with a median age of 50. 14 pts had nodal disease by clinical staging. One pt chose alternative therapy and is not evaluable, and another developed a grade 4 arrhythmia during induction therapy and was removed from the study. There were no other grade 3–4 toxicities during the induction B/FOLFOX. In contrast, 15 of 20 pts (75%) developed at least one grade 3 toxicity during chemoXRT, including diarrhea (9 pts), neutropenia (4 pts), pain (3 pts), fatigue, nausea, and radiation dermatitis (2 pts each) and menorrhagia (1 pt). Grade 4 toxicities were limited to one episode of neutropenia and one pt with nausea, diarrhea and weight loss. Five of 20 pts who have undergone surgery had a pCR (25%). Only one pt has relapsed following treatment. Conclusions: Induction B/FOLFOX is well tolerated by pts with stage II-III rectal cancer, while concurrent B/OX/5- FU/XRT is associated with significant gastrointestinal toxicities, that may be related to OX. The addition of induction B/FOLFOX and B/OX to conventional 5-FU/XRT has not clearly increased the pCR. However, while follow-up is short, there may be an impact on preventing systemic recurrence. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, sanofi-aventis Genentech™ BioOncology, sanofi-aventis
A phase I study of MORAb-003, a humanized monoclonal antibody against folate receptor alpha, in advanced epithelial ovarian cancer
Authors: K. M. Bell-McGuinn, J. A. Konner, N. Pandit-Taskar, S. M. Larson, S. R. Gerst, N. VanderEls, L. Old, S. Weil, M. Phillips, C. A. Aghajanian
Journal: Journal of Clinical Oncology (2008)

5517 Background: MORAb-003 (M3) is a humanized monoclonal antibody against the folate receptor alpha (FRA) which is over- expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. Binding of M3 to FRA can prevent phosphorylation of substrates specific for Lyn kinase, suppress proliferation of cells expressing FRA and tumor growth in vivo of FRA- expressing tumors in xenograft models and mediate FRA-positive tumor cell killing. This open-label, multiple-infusion, first-in-human, dose- escalation trial evaluates the safety, pharmacokinetics (PK), and anti-tumor activity of M3 in patients with platinum-resistant EOC. Methods: Platinum-resistant patients with EOC received 4 weekly infusions of M3. In this dose escalation study 3 subjects were dosed sequentially in each of the following dose cohorts: 12.5, 25, 37.5, 62.5, 100, 200mg/m2, and 6 in the 400mg/m2. Human anti-human antibody (HAHA) and PK analyses were performed. Three subjects received a tracer dose of 111In-labelled M3 with SPECT-CT and planar imaging. Results: The study has been completed. No dose-limiting toxicities, no drug-related serious or severe AEs or trends have been observed. After 1 cycle (4 weeks) of treatment with M3, CT evaluation by RECIST identified 7 subjects who demonstrated stable disease. Four subjects exhibited a decrease in CA-125. Three subjects were given M3 as extended therapy, based on the response seen after one cycle. One subject received 2 additional cycles of M3, resulting in a 48% decrease of CA-125 over a 4-month period. Radiolabelled tracer studies demonstrated significant tumor uptake of labeled M3. HAHA studies were negative for most time points; those above the positive/negative cut point did not appear to be of clinical significance. Preliminary PK analysis demonstrates a half-life appropriate for a humanized monoclonal antibody. Conclusions: M3 appears to be well tolerated in patients with EOC and may have activity in platinum-resistant ovarian cancer. Based on this study and the results of an ongoing exploratory phase 2 study in relapsed EOC, phase 2 studies of M3 in platinum-sensitive and platinum-resistant EOC are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Morphotek, Inc.
International Trials and Pediatric Nephrology
Journal: New England Journal of Medicine (1979)

Despite a few prominent demurrers,1 , 2 most of the many recently published comments on controlled clinical trials3 , 4 have strongly supported the conviction that they are increasingly needed — one admirable worker even arguing that "no treatment regimen should be brought into general use until its advantages had been established by a double-blind controlled trial."4 If there is such general agreement about the need for controlled trials, why are so few properly designed trials of sufficient magnitude being conducted? Why do we continue to read so consistently statements like: "Although these results are promising, firm conclusions must await performance of a controlled . . .
EXPERIMENTAL DIABETES
Journal: JAMA (1924)

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
Tattoos.
Authors: N S Mercer, D M Davies
Journal: BMJ (1991)

Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.