tbuckley/cabot-search huggingface dataset:
Abstract 2764: Effect of PNT2258 combinations with docetaxel, dacarbazine, or vemurafenib on the A375 melanoma xenograft
Authors: Wendi V. Rodrigueza, Christopher Whitehead, Ramzi Mohammad, J. Patrick McGovern, Michael J. Wick, Drew Rasco, Anthony W. Tolcher, Charles L. Bisgaier
Journal: Cancer Research (2012)

Abstract Bcl-2 and bcl-XL are anti-apoptotic proteins that promote drug resistance and enhance tumor cell survival. Bcl-2 gene amplification occurs in 90% of cutaneous melanomas implicating it as a potential target. PNT100 is a 24-mer unmodified DNA oligonucleotide complementary to a non-coding region of bcl-2. PNT2258, is comprised of PNT100 encapsulated in a unique pH tunable nuclear-targeted liposomes termed SMARTICLES®. Preliminary studies demonstrated fluorescently-labeled PNT100 in a SMARTICLE® is delivered to the cell nucleus and that PNT2258 produces dramatic tumor regression in a diffuse large cell lymphoma xenograft, prolonging survival with a coincident decrease in bcl-2 protein. PNT2258 activity in the A375 melanoma model was assessed as a single agent or in combination in two separate studies. Study 1: PNT2258 alone, IV, 5 days/week for 3 weeks, to mice bearing A375 produced growth delays of 10.4, 7.8, and 7.8 days at 12.5, 8.3, and 5.6 mg/kg/dose, respectively. Docetaxel alone, IV weekly x3, produced growth delays of 19.4 (1/10 TFS), 14.8 (1/10 TFS), and 11.5 days at 30, 20, and 13.3mg/kg/dose. Combination therapy produced growth delays of 45.3 (5/10 TFS), 18.9, 28.1 (2/10 TFS), and 25.0 (3/10 TFS) days at 12.5+30, 12.5+20, 5.6+30, and 5.6+20 mg/kg/dose, respectively. Study 2: PNT2258 alone produced a growth delay of 12 days at 15mg/kg/dose. Dacarbazine alone was ineffective at 80 mg/kg/dose IP. Combination therapy was not superior to PNT2258 alone. In contrast, vemurafenib alone (37.5 mg/kg/dose, PO, BIDx18 days) was highly active producing a growth delay in excess of 30 days, as did the combination of PNT2258+vemurafenib. PNT2258 is currently being evaluated for safety and tolerability in a phase Ia clinical trial. Preliminary mouse and human pharmacokinetics suggest that exposure levels in humans are similar to those producing anti-tumor efficacy in mice. Overall, 1) PNT2258+docetaxel produced a greater than additive effect compared to single agents, 2) PNT2258+dacarbazine was not superior to PNT2258 alone, 3) PNT2258+vemurafenib while highly active, was not superior to vemurafinib therapy alone, and 4) therapeutic PNT2258 exposures have been attained in patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2764. doi:1538-7445.AM2012-2764
Falls in acid output.
Authors: J N Hunt
Journal: BMJ (1971)

<h3>ABSTRACT</h3> Urban environments are heterogeneous landscapes of social and environmental features, with important consequences for human-nature entanglements, such as that of mosquito-borne disease. Investigations into this intra-urban heterogeneity in mosquito dynamics find conflicting results, likely due to the complex socio-ecological interactions and the importance of place-based context. Integrative research, which synthesizes multiple disciplines and epistemologies, can help place ecological results into their social context to explore these place-based differences. Here, we develop an integrative approach to understanding spatial patterns of mosquito burdens in urban systems by combining entomological surveys, semi-structured interviews, and sketch maps. Although we found no evidence for a difference in mosquito abundance across an urban gradient, there were differences in individuals’ everyday experiences with mosquitoes. These differences were mediated by how individuals moved through public space and their vulnerability to hazards in these spaces. This example of integrative research illustrates what can be gained from the inclusion of multiple epistemologies, particularly for research in socio-ecological systems.
Clinical Impact of Nonuniform CT-Based Attenuation Correction in Brain Perfusion SPECT/CT Using 99mTc-ECD
Authors: Karim Farid, Slavomir Petras, Xavier Poullias, Nadine Caillat-Vigneron
Journal: Clinical Nuclear Medicine (2013)

Brain perfusion SPECT is commonly used to evaluate patients with cognitive impairments. Physical limits such as attenuation compromise image quality do not allow the most accurate depiction of radionuclide distribution, and thus, application of attenuation correction (AC) has been recommended. Some reports have demonstrated discordances between the uniform (UAC) and nonuniform CT-based correction (NUAC) procedures. The aim was to study the impact of these discordances on visual interpretation and their concordance with clinical symptoms.Twelve patients presenting cognitive impairments were included. Brain perfusion SPECT images were reconstructed using 2 AC methods. Qualitative image assessment was performed as uptake analysis in 21 predefined cortical ROIs for each patient. Interpretation of perfusion patterns was based on a 2-score uptake scale (normal and reduced/pathologic). Variation of uptake scores in UAC- versus NUAC-processed images and their concordance with clinical symptoms were studied.Normal image patterns generated by UAC and NUAC methods were found in 226 (90%) of 252 and in 201 (80%) of 252 ROIs, respectively. No difference between UAC and NUAC methods was found in posterior brain areas. However, differences were recorded in 51 (20%) of 252 ROIs, and this discordance was located in the anterior areas (frontal and temporal lobes), and evaluation changed from normal to pathological patterns using NUAC method. Two years later, patients showing frontal hypoperfusion on NUAC brain SPECT images expressed clinical frontal lobe dysfunctions.Discordances between UAC- and NUAC-processed images impact visual analysis of brain perfusion SPECT images. The NUAC-processed images show a good concordance with clinical symptoms, suggesting that it is an accurate method to correct attenuation.
Abstract 2238: Non-random genetic rearrangements driven highly malignant tumor-cell population dictates the development of high-risk neuroblastoma
Authors: Faizan H. Khan, Satish K. Ramraj, Vijayabaskar Pandian, Sheeja Aravindan, Terence S. Herman, Mohan Natarajan, Natarajan Aravindan
Journal: Cancer Research (2014)

Abstract Ascertaining the driving factors and molecular flow through that confiscate favorable to aggressive high-risk disease has momentous importance in neuroblastoma cure. Herein, we investigated the cytogenetic and tumorigenic/metastatic physiognomies of distinct population of highly malignant (NBP4) cells established from multi-site aggressive tumors after parental (SH-SY5Y) cell xenotransplantation. Karyotyping (G-banding) NBP4 revealed 47 (XX) with six novel non-random chromosomal rearrangements on 1q32, 8p23, 9q34, 15q24, 22q13 (additions), and 7q32 (deletion). Compared to the parental cells, high-resolution array CGH analysis of NBP4 cells and aggressive tumors revealed genetic alterations in chromosomes 1, 7, 8 and 22 corresponding to gain in coding regions of LOC100288142, CD1C, CFHR3, FOXP2, MDFIC, RALYL, CSMD3, SAMD12-AS1, MAL2 and loss in coding regions of ADAM5, LOC400927, APOBEC3B, RPL3, MGAT3, SLC25A17, EP300, L3MBTL2, SERHL, POLDIP3, A4GALT and TTLL1. Compared to SH-SY5Y cells, aggressive NBP4 cells exert stem-like phenotype and under stem-cell-growth conditions demonstrated a profound tumorosphere forming capabilities. Moreover, xenotransplantation of NBP4 cells exhibited high tumor forming capacity and metastatic potential in vivo. Together, these data demonstrate the clonal enrichment of select highly malignant cells drives neuroblastoma progression, and further implies that observed genetic alterations could mediate phenotypic transformation and functional response. Citation Format: Faizan H. Khan, Satish K. Ramraj, Vijayabaskar Pandian, Sheeja Aravindan, Terence S. Herman, Mohan Natarajan, Natarajan Aravindan. Non-random genetic rearrangements driven highly malignant tumor-cell population dictates the development of high-risk neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2238. doi:10.1158/1538-7445.AM2014-2238
Beyond WEIRD: Towards a broad-based behavioral science
Authors: Joseph Henrich, Steven J. Heine, Ara Norenzayan
Journal: Behavioral and Brain Sciences (2010)

Abstract In our response to the 28 (largely positive) commentaries from an esteemed collection of researchers, we (1) consolidate additional evidence, extensions, and amplifications offered by our commentators; (2) emphasize the value of integrating experimental and ethnographic methods, and show how researchers using behavioral games have done precisely this; (3) present our concerns with arguments from several commentators that separate variable “content” from “computations” or “basic processes”; (4) address concerns that the patterns we highlight marking WEIRD people as psychological outliers arise from aspects of the researchers and the research process; (5) respond to the claim that as members of the same species, humans must have the same invariant psychological processes; (6) address criticisms of our telescoping contrasts; and (7) return to the question of explaining why WEIRD people are psychologically unusual. We believe a broad-based behavioral science of human nature needs to integrate a variety of methods and apply them to diverse populations, well beyond the WEIRD samples it has largely relied upon.
Naïve optimality: Subjects' heuristics can be better motivated than experimenters' optimal models
Authors: Jonathan D. Nelson
Journal: Behavioral and Brain Sciences (2009)

Is human cognition best described by optimal models, or by adaptive but suboptimal heuristic strategies? It is frequently hard to identify which theoretical model is normatively best justified. In the context of information search, naïve subjects' heuristic strategies are better motivated than some "optimal" models.
Rethinking Professional Courtesy
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (1993)

Professional courtesy, the provision of care without charge to physicians and their immediate families, is a long-standing tradition in the medical profession. The practice, as described in 1803 by Thomas Percival in Medical Ethics, reflects the interdependence of “medical men, under the pressure of sickness, either as affecting themselves or their families”1. Professional courtesy was initially envisioned as a means of improving care, not of offering physicians a bargain. The American Medical Association's first code of ethics, issued in 1847, was based in large part on Percival's work. The code noted that “a physician afflicted with disease is usually . . .
ENCEPHALITIS IN THE YAKIMA VALLEY
Authors: H. J. Shaughnessy
Journal: JAMA (1941)

<h3>To the Editor:—</h3> We would like to take exception to the statement made by Dr. W. W. Hammon (Encephalitis in the Yakima Valley,The Journal, July 19, p. 161) to the effect that we had recommended that physicians use hyperimmune rabbit serum in the treatment of Western equine encephalomyelitis in man. Actually our report inThe Journal, Sept. 28, 1940, was a factual account of the results of treating the experimental disease in mice and guinea pigs with specific hyperimmune rabbit serum. The purpose of our investigations was to determine whether a virus disease could be treated with serum after the onset of symptoms. We did not recommend or even imply that our serum be used in treatment of the disease in man. Other statements in the article made by Dr. Hammon are open to question. The first of these is that serum treatment in man would not be feasible
Severe Upper Gastrointestinal Tumor Bleeding: Endoscopic Findings, Treatment, and Outcome
Authors: T. J. Savides, D. M. Jensen, J. Cohen, G. M. Randall, T. O. G. Kovacs, E. Pelayo, S. Cheng, M. E. Jensen, H.-Y. Hsieh
Journal: Endoscopy (1996)

Background and Study Aims: The aim of the present study was to review endoscopic findings, treatment, and clinical outcomes in patients with severe upper gastrointestinal bleeding due to tumors.
Prevention of variceal rebleeding by propranolol: Can “nonresponders” be identified?
Authors: A. K. Burroughs
Journal: Hepatology (1986)

Between October, 1981 and December 1983, 46 consecutive unselected cirrhotic patients who had been admitted for variceal hemorrhage were assigned to propranolol for the prevention of variceal rebleeding and followed for a mean period of 13.3 months (ranges: 1 day, 45 months). At the time of inclusion, 87 p. 100 of patients had alcoholic cirrhosis: ascites was present in 43 p. 100, jaundice in 43 p. 100 and encephalopathy in 33 p. 100 of cases. The goal of this retrospective study was to assess the effectiveness of propranolol in these unselected patients and to determine variables associated with a high rebleeding rate. Twenty-four patients (52 p. 100) rebled from esophageal varices within a mean time of 8.2 months (range: 6 days, 39 months) and 12 of these patients died. The percentage of patients who rebled from varices was 27 p. 100 at 6 months, 43 p. 100 at 1 year, 52 p. 100 at 18 months. Patients with ascites at the time of inclusion were 3.5 times more likely to rebleed than patients without ascites (p = 0.007). Patients with jaundice (total bilirubin ≥ 50 μmol/l) were 3.1 times more likely to rebleed than patients without jaundice (p = 0.01). One year after the beginning of this treatment, the probability of rebleeding was 19 p. 100 in the 17 Pugh-Child class A cirrhotic patients, 60 p. 100 in the 15 class B patients, 55 p. 100 in the 14 class C patients. Neither proper acceptance in taking propranolol nor alcohol withdrawal were associated with significantly modified risks of rebleeding in these unselected alcoholic patients.
The Mild Geographer
Authors: Samuel Vaisrub
Journal: JAMA (1978)

Unlike the discoveries of Copernicus and Galileo, which had a pronounced impact on poetry, the discovery of the circulation did not quicken the pulses of poets in Harvey's time nor of those in the centuries to follow. Apparently, the movement of planets in infinite space appealed to the poetic imagination more than did the motion of the heart.  heart has always inspired poets, but only as a seat of emotion. As a circulatory pump, it did not stir the muse.  It is thus a rare treat to chance upon a poem bearing the title Dr. William Harvey. In this poem, Walter de la Mare (1873 to 1956) depicts Harvey as a mild geographer, who set not his mark/On unknown seas, lakes, rivers vast in flood, but rather to ponder on The motions of man's blood. Contrasting this inspiring image with the contemptuous (crackbrained, childish) references made by some of
The l-arginine/nitric oxide pathway contributes to the acute release of tissue plasminogen activator in vivo in man
Authors: David E Newby, Robert A Wright, Pamela Dawson, Christopher A Ludlam, Nicholas A Boon, Keith A.A Fox, David J Webb
Journal: Cardiovascular Research (1998)

Objective: Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, l-NG-monomethylarginine (l-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. Methods: Blood flow and plasma fibrinolytic and haemostatic factors were measured in both forearms of 8 healthy male volunteers who received unilateral brachial artery infusions of substance P (2–8 pmol/min) and l-NMMA (1–4 μg/min). Results: Substance P caused dose-dependent increases in blood flow (P<0.001) and plasma t-PA antigen (P=0.04) and activity (P<0.001) concentrations confined to the infused forearm, but had no effect on plasminogen activator inhibitor type 1 (PAI-1) or von Willebrand factor concentrations. In the presence of l-NMMA, substance P again caused significant increases in blood flow (P<0.001) and t-PA antigen (P=0.003) and activity (P<0.001) concentrations but these increases were significantly less than with substance P alone (P<0.001, P=0.05 and P<0.01, respectively). l-NMMA alone significantly reduced blood flow in the infused arm, but had no measurable effect on t-PA or PAI-1 concentrations. Conclusions: The l-arginine/nitric oxide pathway contributes to substance P-induced t-PA release in vivo in man. This provides an important potential mechanism whereby endothelial dysfunction increases the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.
Graves' Disease in a Patient With Ectopic Mediastinal Thyroid
Authors: Gozde Daglioz Gorur, Serkan Isgoren, Yusuf Ziya Tan, Zafer Utkan, Hakan Demir, Fatma Berk
Journal: Clinical Nuclear Medicine (2011)

Abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue. Ectopic mediastinal goiters are somewhat uncommon developmental anomalies, accounting for less than 1% of all thyroid ectopies. Graves' disease within mediastinal goiter is a very rare entity, described only in few cases in English literature. Pretracheal thyroidectomy alone does not cure Graves' disease and can stimulate growth of the ectopic tissue in such cases.
Humidification of Inspired Air
Authors: L. B. W. Jongkees
Journal: BMJ (1975)

tion by binding to ristocetin and not by an effect on the platelets or the ristocetin cofactor.There is no evidence that our ob- servation reflects an influence of Haemaccel on the haemostatic mechanism in vivo.All evidence suggests that this inhibition is solely an in-vitro phenomenon.-Weare, etc.,
Milestones, tombstones, and sex education
Authors: Douglas Kamerow
Journal: BMJ (2007)

Over the past several weeks, the BMJ has been conducting a poll of readers to determine the world's greatest medical milestone since the journal began publishing in 1840. Experts provided 15 candidate advances, ranging from immunizations to birth control pills to x-rays, and more than 11,000 readers voted. In addition to this week's regular journal, we are publishing a supplement with articles about each of the candidates and why they deserved to be …
IDEC-C2B8 (Rituximab) Anti-CD20 Monoclonal Antibody Therapy in Patients With Relapsed Low-Grade Non-Hodgkin's Lymphoma
Authors: David G. Maloney, Antonio J. Grillo-López, Christine A. White, David Bodkin, Russell J. Schilder, James A. Neidhart, Nalini Janakiraman, Kenneth A. Foon, Tina-Marie Liles, Brian K. Dallaire, Ken Wey, Ivor Royston, Thomas Davis, Ronald Levy
Journal: Blood (1997)
Stimulatory effect of inflammatory cytokines on alpha 1-antichymotrypsin expression in human lung-derived epithelial cells.
Authors: J Cichy, J Potempa, R K Chawla, J Travis
Journal: Journal of Clinical Investigation (1995)

Although it is a well known fact that hepatocytes are the primary source of plasma proteinase inhibitors, including alpha 1-antichymotrypsin, this protein has also been detected in lung epithelial cells, which may suggest its local production. We have demonstrated that lung-derived epithelial cells are capable of synthesizing high levels of alpha 1-antichymotrypsin. In normal bronchial epithelial cells, as well as in the HTB55 human adenocarcinoma cell line, alpha 1-antichymotrypsin synthesis was under the control of inflammatory cytokines, of which oncostatin M was the most potent stimulator. This finding is consistent with a role for this inhibitor in protecting the lung epithelium from damage by chymotrypsin-like enzymes released from phagocytes such as neutrophils following pathogen invasion.
Mineralocorticoid and glucocorticoid effects on 31,000- and 29,000-dalton proopiomelanocortin in rat anterior pituitary and neurointermediate lobe.
Authors: B A Khalid, A T Lim, D R Fraillon, J W Funder
Journal: Journal of Clinical Investigation (1982)

The effects of adrenal steroids on proopiomelanocortin (POMC) levels in rat pituitary have been studied by two-dimensional gel electrophoresis. In intact rats the relative abundance of POMC was much higher in the neurointermediate lobe (N-IL) than in anterior pituitary (AP); in both tissues the predominant species appeared to be of 29,000-dalton (29K) molecular mass, with lesser amounts of a 31K form. In both tissues, the 31K and 29K forms showed multiple spots, consistent with different degrees of sialoglycosylation. Adrenalectomy was followed by a marked increase in AP levels of POMC, and a marked decrease in N-IL levels. In adrenalectomized rats, dexamethasone administration did not affect N-IL levels of POMC, but suppressed 35S incorporation into POMC in AP in a dose-related manner; deoxycorticosterone showed minimal effects on AP levels of POMC, but progressively elevated N-IL levels; 9 alpha fluorocortisol (9 alpha fF) progressively both suppressed AP levels, and raised N-IL levels of POMC. Estimation of immunoreactive (ir) ACTH and ir-beta-endorphin in parallel samples showed an elevation of N-IL levels in response to mineralocorticoids (deoxycorticosterone, 9 alpha fF), and a paradoxical elevation of AP levels in response to glucocorticoids (dexamethasone, 9 alpha fF) compared with oil-injected adrenalectomized controls. We conclude (a) that glucocorticoids suppress the secretion of ir-ACTH and ir-beta-endorphin to a greater extent than they inhibit the synthesis of POMC; (b) that mineralocorticoids specifically elevate the N-IL levels of both POMC and its immunoreactive product (beta-endorphin).
Pseudoalbuminuria Due To Bunamiodyl
Authors: John H. Grimm
Journal: JAMA (1960)

Pseudoalbuminuria in conjunction with the use of orally administered gallbladder contrast media, as first reported by Seedorf and others in 1950 1 and in subsequent papers, 2-5 is well established. The introduction of a new contrast medium, bunamiodyl (Orabilex) and its adoption for general use in our hospital in 1959 prompted the present study. The chemical formula of bunamiodyl is 3(3-butyrylamino-2,4,6-triiodophenyl)-2-ethyl sodium acrylate. It contains 57% iodine in organic form. It is somewhat soluble in water, and excretion is largely renal.  A series of 100 patients was tested. Menstruating women, as well as patients with true albuminuria and urinary infections, were excluded. The standard dosage for each patient was 6 capsules (4.5 Gm.) of bunamiodyl. Inasmuch as the routine laboratory procedure in this hospital for detection of albumin is the use of sulfosalicylic acid and effervescent base, this was the method chosen. A solution of 4 tablets dissolved in 30