tbuckley/cabot-search huggingface dataset:
Reflex Immunohistochemistry and Microsatellite Instability Testing of Colorectal Tumors for Lynch Syndrome Among US Cancer Programs and Follow-Up of Abnormal Results
Authors: Laura C. Beamer, Marcia L. Grant, Carin R. Espenschied, Kathleen R. Blazer, Heather L. Hampel, Jeffrey N. Weitzel, Deborah J. MacDonald
Journal: Journal of Clinical Oncology (2012)

Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (MSI) are well-established tools to screen for Lynch syndrome (LS). Although many cancer centers have adopted these tools as reflex LS screening after a colorectal cancer diagnosis, the standard of care has not been established, and no formal studies have described this practice in the United States. The purpose of this study was to describe prevalent practices regarding IHC/MSI reflex testing for LS in the United States and the subsequent follow-up of abnormal results.A 12-item survey was developed after interdisciplinary expert input. A letter of invitation, survey, and online-survey option were sent to a contact at each cancer program. A modified Dillman strategy was used to maximize the response rate. The sample included 39 National Cancer Institute-designated Comprehensive Cancer Centers (NCI-CCCs), 50 randomly selected American College of Surgeons-accredited Community Hospital Comprehensive Cancer Programs (COMPs), and 50 Community Hospital Cancer Programs (CHCPs).The overall response rate was 50%. Seventy-one percent of NCI-CCCs, 36% of COMPs, and 15% of CHCPs were conducting reflex IHC/MSI for LS; 48% of the programs used IHC, 14% of the programs used MSI, and 38% of the programs used both IHC and MSI. One program used a presurgical information packet, four programs offered an opt-out option, and none of the programs required written consent.Although most NCI-CCCs use reflex IHC/MSI to screen for LS, this practice is not well-adopted by community hospitals. These findings may indicate an emerging standard of care and diffusion from NCI-CCC to community cancer programs. Our findings also described an important trend away from requiring written patient consent for screening.
Survival following coronary angioplasty versus coronary artery bypass surgery in anatomic subsets in which coronary artery bypass surgery improves survival compared with medical therapy
Authors: Peter B Berger, James L Velianou, Helen Aslanidou Vlachos, Frederick Feit, Alice K Jacobs, David P Faxon, Michael Attubato, Norma Keller, Michael L Stadius, Bonnie H Weiner, David O Williams, Katherine M Detre
Journal: Journal of the American College of Cardiology (2001)
A Commentary on Treatment at Random: The Ultimate Science or the Betrayal of Hippocrates?
Authors: Samuel Wieand, Kate Murphy
Journal: Journal of Clinical Oncology (2004)

Spyros Retsas, MD, addresses a controversial issue in oncology (and medicine in general): the proper role of randomized trials when treating individual patients. He ultimately concludes, “...the randomized trial emerges as a deficient research tool both on deontologic and methodologic grounds.” We have been asked to provide a commentary as a companion to his discussion. Dr Retsas has divided his discussion into three broad categories, with a corresponding position regarding each category: philosophical (equipoise, or absolute uncertainty, cannot exist in clinical practice); ethical (beneficence does not allow the physician to randomly assign patients because randomized clinical trials are not treatment, but research); and methodologic (randomized clinical trials are deficient research).
Large-scale gene discovery in the pea aphid Acyrthosiphon pisum(Hemiptera)
Authors: Beatriz Sabater-Muñoz, Fabrice Legeai, Claude Rispe, Joël Bonhomme, Peter Dearden, Carole Dossat, Aymeric Duclert, Jean-Pierre Gauthier, Danièle Giblot Ducray, Wayne Hunter, Phat Dang, Srini Kambhampati, David Martinez-Torres, Teresa Cortes, Andrès Moya, Atsushi Nakabachi, Cathy Philippe, Nathalie Prunier-Leterme, Yvan Rahbé, Jean-Christophe Simon, David L Stern, Patrick Wincker, Denis Tagu
Journal: Genome biology (2006)

Abstract Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum . An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect.
The sequential appearance of Ia-like antigens and two different complement receptors during the maturation of human neutrophils.
Authors: G D Ross, C I Jarowski, E M Rabellino, R J Winchester
Journal: The Journal of Experimental Medicine (1978)

Ia antigens and two different types of complement (C) receptors appeared on membrane surfaces in a distinct sequence during the maturation of human neutrophils. Taking advantage of the finding that neutrophil celll density increased with maturation, density gradient centrifugation was used to separate neutrophils into fractions that were greatly enriched in cells representing individual stages of differentiation. Myeloblasts, the earliest cells recognized in the myeloid series of both normal and myelogenous leukemic individuals, expressed Ia determinants, whereas Ia determinants were absent or diminished on the majority of promyelocytes and completely undetectable on more mature granulocytes. Double marker studies demonstrated that Ia determinants were lost from the membrane of developing myeloid cells before the appearance of any type of C receptor. In the next phase of maturation defined by surface markers, neutrophils acquired a CR2-type C receptor (C3d receptor) that was similar in specificity to CR2 of B lymphocytes. This stage of maturation approximately corresponded to the myelocyte-metamyelocyte stage defined by standard morphologic criteria, and preceded the third stage of surface marker maturation when developing neutrophils began to express CR1-type C receptors (immune adherence, C4b-C3b receptors) in addition to CR2. In the final stage of surface marker-defined maturation, CR2 was lost from high density polymorphonuclear neutrophils and CR1 was maximally expressed. Normal blood polymorphonuclear neutrophils contained only 17% of CR2-bearing cells and these were shown to be of lower density than the majority of neutrophils that expressed only CR1. There was some variation in the correlation of surface marker expression and maturation stage defined by morphologic criteria, but in all cases the sequence of marker appearance was the same: Ia leads to CR2 leads to CR1CR2 leads to CR1.
Bacterial Endocarditis Following Homograft Replacement of the Aortic Valve
Authors: PATRICIA M. CLARKSON, BRIAN G. BARRATT-BOYES
Journal: Circulation (1970)

Endocarditis was encountered on an aortic homograft valve in 14 of 539 patients, giving a total incidence of 2.6%. It was an early postoperative complication in five patients (0.9%), and only one of these survived. Four hundred and six hospital survivors were followed for periods up to 76 mo. Nine of these patients (2.2%) developed infection of the homograft valve 11 to 66 mo postoperatively and four survived. Late endocarditis occurred more commonly in patients with a history of endocarditis prior to operation ( P =0.005). In only one of the nine patients with late endocarditis was the infection related to a peripheral leak around the graft. Most patients with late endocarditis rapidly developed severe homograft valve incompetence, which was the cause of death in four of the nine. Six patients were reoperated on and three of these survived.
TCT-48 Comparison of long-term outcome between transradial approach and transfemoral approach for patients with ST-segment elevation myocardial infarction.
Authors: Ryuma Ishihara, Atsushi Tosaka, Toshio Katagiri, Yuriko Sato, Taisuke Mizumura, Youichi Sugimura, Masakazu Tsutsumi, Naoyuki Abe, Takashi Miura
Journal: Journal of the American College of Cardiology (2013)
Characterizing alterations in the pulmonary surfactant system in a rat model of Pseudomonas aeruginosa pneumonia
Authors: J Vanderzwan, L McCaig, S Mehta, M Joseph, J Whitsett, DG McCormack, JF Lewis
Journal: European Respiratory Journal (1998)

Bacterial pneumonia remains a significant cause of patient morbidity and mortality worldwide. Pulmonary surfactant serves to maintain homeostasis in the lung through the maintenance of alveolar stability and the regulation of the alveolar immune response. The purpose of this study was to characterize the lung injury and associated surfactant alterations in a rat model of acute Pseudomonas aeruginosa pneumonia. Pneumonia was induced in male Sprague-Dawley rats via intratracheal injection of 0.2 ml, phosphate-buffered saline (PBS) containing P. aeruginosa (6x10(8) colony-forming units x mL(-1)). Control animals received 0.2 mL sterile PBS. Twenty-four hours after inoculation, the pneumonia group (PN) exhibited clinical signs of pneumonia including deficits in gas exchange, leukopenia and elevated arterial lactate levels. Morphological assessment confirmed the presence of pneumonia with airspaces filled with polymorphonuclear cells. Lung homogenate analysis demonstrated evidence of bacterial colonization of pneumonic lung tissue. Lung compliance was also significantly lower in the PN group. Lung lavage analysis of PN rats revealed the pooled surfactant levels to be lower and the surfactant function reduced compared to control rats. Surfactant composition was also found to be altered in PN rats. These results demonstrate that in Pseudomonas aeruginosa pneumonia, the pulmonary surfactant system is both poorly functioning and reduced in quantity. These alterations may contribute to the lung dysfunction characteristic of this disorder.
Effects of ultraviolet light on the eye: role of protective glasses.
Authors: F J van Kuijk
Journal: Environmental Health Perspectives (1991)

Global atmospheric changes such as depletion of ozone in the stratosphere are thought to lead to increased levels of ultraviolet radiation on earth. This can have adverse effects on human health, and long-term effects of ultraviolet light on the eye are of increasing concern. Ultraviolet light exposure to the eye has been associated with cataract formation and retinal degeneration. In both cases, it is hypothesized that ultraviolet light can initiate formation of free radicals, which can cause protein modification and lipid peroxidation. Several procedures can be recommended to prevent ultraviolet light damage to the eye, such as the use of suitable protective glasses when outdoors.
Phase I Trial of Concurrent Twice-Weekly Recombinant Human Interleukin-12 Plus Low-Dose IL-2 in Patients With Melanoma or Renal Cell Carcinoma
Authors: Jared A. Gollob, Korina G. Veenstra, Robert A. Parker, James W. Mier, David F. McDermott, Daniel Clancy, Linda Tutin, Henry Koon, Michael B. Atkins
Journal: Journal of Clinical Oncology (2003)

To maintain interferon gamma (IFNgamma) induction by recombinant human interleukin-12 (rhIL-12) and enhance its activity against melanoma and renal cell cancer, a regimen of twice-weekly intravenous (IV) rhIL-12 was modified to include concurrent low-dose subcutaneous (SC) IL-2 in a phase I dose escalation study.Patients received 6-week cycles of twice-weekly IV rhIL-12 at doses of 300 to 500 ng/kg. Midway through cycle 1, low-dose SC IL-2 was added. The IL-2 was escalated from 0.5 to 6.0 MU/m2. Grade 3 elevations of hepatic ALT, AST, or alkaline phosphatase were not considered dose-limiting unless values were more than 10 times normal. During cycle 1, patients underwent immune monitoring to assess the effect of IL-2 on lymphocyte activation and cytokine production induced by rhIL-12.Twenty-eight patients were enrolled onto the study. The maximum-tolerated dose (MTD) was 500 ng/kg rhIL-12 plus 3 MU/m2 IL-2. Toxicities related to the addition of IL-2 at the MTD included fever or chills, anemia, fatigue, nausea or vomiting, and orthostatic hypotension. At the MTD, IL-2 significantly augmented IFNgamma and IFNgamma-inducible protein-10 production by rhIL-12 and led to a three-fold expansion of natural killer cells. There was one major clinical response (partial response) as well as two pathologic responses; all occurred in melanoma patients. Stable disease for three to six cycles was only observed at or above the MTD in melanoma and renal cell cancer patients.The addition of concurrent low-dose IL-2 to rhIL-12 is well tolerated, restores and maintains immune activation by rhIL-12, and has clinical activity. This regimen should be further investigated in phase II studies in untreated patients with melanoma or renal cell cancer and in other rhIL-12-responsive malignancies.
Aminophylline increases ventilation and abdominal muscle contractility in awake canines
Authors: Jenny Vannessa Jagers, Michael Ji, John Kortbeek, Paul A. Easton
Journal: European Respiratory Journal (2012)

Aminophylline (Amino) is still used in treatment of COPD. However, effects of Amino on ventilation and respiratory muscles are uncertain. Utilizing implants in awake canines, we examined the effects of Amino on costal diaphragm (Jagers et al. Resp Phys, 2009). Here we study the effect of Amino on abdominal muscles of expiration, by measurement of the transversus abdominis (TA).

Sonomicrometry transducers and EMG electrodes were implanted in the left TA. After recovery, the animals were studied awake, breathing through a mask. Airflow, ETCO2, heart rate, muscle length, and moving average EMG were recorded during room air, and CO2 stimulation, before and after Amino. Output included breath-by-breath breathing pattern, muscle shortening, peak EMG, PaCO2 and heart rate. Results are shown at room air and 3 levels of CO2.

For N= 6 dogs (mean wgt 29.8 kg) studied after 25 days, minute ventilation, tidal volume, and respiratory frequency increased significantly with Amino, during resting breathing and all levels of CO2. Mean aminophylline was 72 umol/L (therapeutic range 55-110 umol/L). TA shortening increased significantly with Amino while TA EMG activity remained unchanged, consistent with increased contractility of the TA with Amino.

![Figure][1] 



In awake, intact, canines, after Amino, TA contractility is increased, as shown by greater muscle shortening per EMG. This enhanced action of expiratory muscles occurs at therapeutic levels of Amino.

 [1]: pending:yes
Treatment of achalasia.
Authors: S Banerjee, S Pugh, P M Smith
Journal: Gut (1993)

<h3>ABSTRACT</h3> <h3>Background</h3> Mean active degree is an important proxy measure of cross-sectional network connectivity commonly used in HIV/STI epidemiology research. No current studies have compared measurement methods of mean degree using cross-sectional surveys for men who have sex with men (MSM) in the United States. <h3>Methods</h3> We compared mean degree estimates based on reported ongoing main and casual sexual partnerships (<i>current method</i>) against dates of first and last sex (<i>retrospective method</i>) from 0–12 months prior to survey date in ARTnet, a cross-sectional survey of MSM in the U.S. (2017–2019). ARTnet collected data on the number of sexual partners in the past year but limited reporting on details used for calculating mean degree to the 5 most recent partners. We used linear regression to understand the impact of truncated partnership data on mean degree estimation. <h3>Results</h3> Retrospective method mean degree systematically decreased as the month at which it was calculated increased from 0–12 months prior to survey date. Among participants with &gt;5 partners in the past year compared to those with ≤5, the average change in main degree between 12 and 0 months prior to survey date was −0.05 (95% CI: −0.08, −0.03) after adjusting for race/ethnicity, age, and education. The adjusted average change in casual degree was −0.40 (95% CI: −0.45, −0.35). <h3>Conclusions</h3> The retrospective method underestimates mean degree for MSM in surveys with truncated partnership data, especially for casual partnerships. The current method is less prone to bias from partner truncation when the target population experiences higher cumulative partners per year. <h3>Summary</h3> Survey designs can lead to potential bias, such as underestimation, in the measurement of mean active degree in sexual networks of men who have sex with men.
Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs.
Authors: B D Guth, E Thaulow, G Heusch, R Seitelberger, J Ross
Journal: Circulation Research (1990)

To study the effect of selective alpha 1- or alpha 2-adrenergic blockade on the myocardial contractile and chronotropic response to exercise, 29 dogs were chronically instrumented with a sonomicrometer for measuring myocardial wall thickness and a micromanometer for measuring left ventricular pressure. During treadmill exercise, either the selective alpha 1-blocker prazosin (80 micrograms/kg, n = 12) or the alpha 2-blocker idazoxan (80 micrograms/kg, n = 8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. alpha 1-Adrenoceptor blockade, like alpha 2-adrenoceptor blockade, was found to cause significant increases in systolic wall thickening, thickening velocity, heart rate, and left ventricular contractility, indicating an increase in inotropic state that was comparable to that with alpha 2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective alpha 1-blockade by using either systemic angiotensin II infusion (n = 6) or inflation of an intra-aortic balloon (n = 6) did not prevent the observed increases in wall thickening, heart rate, and left ventricular contractility. In four of the dogs treated with prazosin, the norepinephrine concentration in the coronary sinus was found to more than double after alpha 1-blockade. beta-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by alpha 1- or alpha 2-blockade. Selective alpha-adrenergic blockade during adrenergic activation by intravenous norepinephrine infusion, in contrast to exercise, had no effect on wall thickening, heart rate, or left ventricular contractility. These data indicate that selective alpha 1-adrenergic blockade, like selective alpha 2-adrenergic blockade, causes a significant augmentation of heart rate and left ventricular contractility in the dog during dynamic exercise. These data are consistent with the hypothesis that this occurs through a presynaptic disinhibition of neural norepinephrine release mediated by a prejunctional alpha 1-adrenoceptor.
Consciousness as phenomenal ether?
Authors: Antti Revonsuo
Journal: Behavioral and Brain Sciences (2003)

The Gestalt Bubble model of visual consciousness is a courageous attempt to take the first-person perspective as primary in the study of consciousness. I have developed similar ideas as the Virtual Reality Metaphor of consciousness (Revonsuo 1995; 2000). I can, hence, only agree with Lehar about the general shape of a proper research strategy for the study of consciousness. As to the metaphysical basis of the research program, I have, however, several reservations about panexperientialism.
Virus-Associated Tumor Imaging by Induction of Viral Gene Expression
Authors: De-Xue Fu, Yvette C. Tanhehco, Jianmeng Chen, Catherine A. Foss, James J. Fox, Victor Lemas, Ja-Mun Chong, Richard F. Ambinder, Martin G. Pomper
Journal: Clinical Cancer Research (2007)

Abstract Purpose: EBV and other herpesviruses are associated with a variety of malignancies. The EBV thymidine kinase (TK) is either not expressed or is expressed at very low levels in EBV-associated tumors. However, EBV-TK expression can be induced in vitro with several chemotherapeutic agents that promote viral lytic induction. The goal of this study is to image EBV-associated tumors by induction of viral TK expression with radiolabeled 2′-fluoro-2′-deoxy-β-d-5-iodouracil-arabinofuranoside (FIAU). Experimental Design: Immunoblot, luciferase reporter assay, and in vitro assay with [14C]FIAU were used to show the effects of bortezomib on the induction of lytic gene expression of EBV-associated tumor cells. In vivo imaging and ex vivo biodistribution studies with [125I]FIAU on EBV-associated tumors were done to visualize and confirm, respectively, the EBV(+) tumor–specific effects of bortezomib. Results: In vitro assays with [14C]FIAU and ex vivo biodistribution studies with [125I]FIAU showed that uptake and retention of radiolabeled FIAU was specific for cells that express EBV-TK. Planar gamma imaging of EBV(+) Burkitt's lymphoma xenografts in severe combined immunodeficient mice showed [125I]FIAU localization within tumors following treatment with bortezomib. Conclusions: These results indicate the feasibility of imaging chemotherapy-mediated viral lytic induction by radiopharmaceutical-based techniques such as single photon emission computed tomography and positron emission tomography.
Mastermind-like 1 Is a Specific Coactivator of β-Catenin Transcription Activation and Is Essential for Colon Carcinoma Cell Survival
Authors: Marie-Clotilde Alves-Guerra, Chiara Ronchini, Anthony J. Capobianco
Journal: Cancer Research (2007)

Abstract Misregulation of the Wnt signaling pathway has been linked to many human cancers including colon carcinoma and melanoma. The primary mediator of the oncogenic effects of the Wnt signaling pathway is β-catenin. Accumulation of nuclear β-catenin and transcription activation of lymphoid enhancer factor 1 (LEF1)/T-cell factor (TCF) target genes underlie the oncogenic activity. However, the mechanism of β-catenin–mediated transcriptional activation remains poorly understood. In this study, we identified Mastermind-like 1 (Maml1), which is thought to be a specific coactivator for the Notch pathway, as a coactivator for β-catenin. We found that Maml1 participates in the Wnt signaling by modulating the β-catenin/TCF activity. We show in vivo that Maml1 is recruited by β-catenin on the cyclin D1 and c-Myc promoters. Importantly, we show that Maml1 functions in the Wnt/β-catenin pathway independently of Notch signaling. Finally, we show that the knockdown of Mastermind-like family proteins in colonic carcinoma cells results in cell death by affecting β-catenin–induced expression of cyclin D1 and c-Myc. This is the first demonstration of a role for the Mastermind-like family in another signaling pathway and that the knockdown of Mastermind-like family function leads to tumor cell death. [Cancer Res 2007;67(18):8690–8]
Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node
Authors: A Zaza
Journal: Cardiovascular Research (2001)

Objective: Clinical indexes of autonomic activity are based on the analysis of sinus cycle length and of its variability. A common assumption underlying this practice is that neural activity and cycle length may be linearly related. Recent experimental evidence suggests that such an assumption may not be correct; indeed, the relation linking autonomic agonist concentration to cycle length was found to be strongly non-linear in single sinoatrial myocytes. In the present work, we (i) test compatibility of non-linearity of neural modulation of cycle length (CL) with previous experimental and clinical observations; (ii) evaluate its implications for what concerns the interpretation of time- and frequency-domain parameters of heart rate variability (HRV) and baroreflex sensitivity (BRS). Conclusions: Non-linearity of neural modulation of CL may result in an intrinsic rate-dependency of autonomic indexes, with the exception of normalised frequency-domain indexes (e.g. the low frequency/high frequency (LF/HF) ratio), which appear to be devoid of intrinsic rate-dependency. This characteristic may not limit the value of HRV indexes and BRS in risk stratification, but has to be taken into account in their pathophysiological interpretation.