tbuckley/cabot-search huggingface dataset:
Cheating at medical school
Authors: R. Smith
Journal: BMJ (2000)

<h3>Abstract</h3> Eradicating invasive species from islands is a proven method for safeguarding threatened and endangered species from extinction. Island eradications can deliver lasting benefits, but require large up-front expenditure of limited conservation resources. The choice of islands must therefore be prioritised. Numerous tools have been developed to prioritise island eradications, but none fully account for the risk of those eradicated species later returning to the island: reinvasion. In this paper, we develop a prioritisation method for island eradications that accounts for the complexity of the reinvasion process. By merging spatially-explicit metapopulation modelling with stochastic dynamic optimisation techniques, we construct a decision-support tool that optimises conservation outcomes in the presence of reinvasion risk. We applied this tool to two different case studies – rat (<i>Rattus rattus</i>) invasions in the Seaforth archipelago in New Zealand, and cane toad (<i>Rhinella marina</i>) invasions in the Dampier archipelago in Australia – to illustrate how state-dependent optimal policies can maximise expected conservation gains. In both case studies, incorporating reinvasion risk dramatically altered the optimal order of island eradications, and improved the potential conservation benefits. The increase in benefits was larger in Dampier than Seaforth (42% improvement versus 6%), as a consequence of both the characteristics of the invasive species, and the arrangement of the islands. Our results illustrate the potential consequences of ignoring reinvasion risk, and demonstrate that including reinvasion in eradication prioritisation can dramatically improve conservation outcomes.
Gamma rhythms as liminal operators in sensory processing
Authors: Miles A. Whittington
Journal: Behavioral and Brain Sciences (2004)

Gamma rhythms are associated with external and internal sensory processing. Within the conceptual framework of “top-down” and “bottom-up” processing, this suggests that gamma represents a format common to both camps. As these oscillations facilitate communication in the temporal domain, they may represent a mechanism by which top-down and bottom-up processing can interact. A breakdown in this interaction may lead to hallucinations.
Diabetes and Function in Different Cognitive Systems in Older Individuals Without Dementia
Authors: Zoe Arvanitakis, Robert Smith Wilson, Yan Li, Neelum Thanik Aggarwal, David Alan Bennett
Journal: Diabetes Care (2006)

OBJECTIVE—To examine the relation of type 2 diabetes to the level of function in five different cognitive systems in older individuals without dementia. RESEARCH DESIGN AND METHODS—Participants were 882 older men and women without dementia participating in the Rush Memory and Aging Project, a longitudinal clinical-pathological study of aging and dementia. They underwent uniform evaluations, which included clinical classification of dementia, and detailed cognitive function testing from which previously established summary measures of episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability, and global cognition were derived. Diabetes was identified by history and direct medication inspection. RESULTS—Diabetes was present in 116 (13%) participants. In separate linear regression models controlling for age, sex, and education, diabetes was associated with lower levels of semantic memory (P &amp;lt; 0.001) and perceptual speed (P = 0.005), but not with episodic memory, working memory, or visuospatial ability or with a measure of global cognition. The associations of diabetes with cognition were reduced when controlling for several vascular variables, and the associations were substantially stronger in current smokers than in individuals who never smoked or formerly smoked. CONCLUSIONS—These results suggest that type 2 diabetes is associated with cognitive impairment, especially in semantic memory and perceptual speed and that these effects may be modified by smoking status.
C-Reactive Protein As a Marker of Melanoma Progression
Authors: Shenying Fang, Yuling Wang, Dawen Sui, Huey Liu, Merrick I. Ross, Jeffrey E. Gershenwald, Janice N. Cormier, Richard E. Royal, Anthony Lucci, Christopher W. Schacherer, Julie M. Gardner, John D. Reveille, Roland L. Bassett, Li-E Wang, Qingyi Wei, Christopher I. Amos, Jeffrey E. Lee
Journal: Journal of Clinical Oncology (2015)

To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival.Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests.Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression.CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma.
The Molecular Basis for Oat Intolerance in Patients with Celiac Disease
Authors: Helene Arentz-Hansen, Burkhard Fleckenstein, Øyvind Molberg, Helge Scott, Frits Koning, Günther Jung, Peter Roepstorff, Knut E. A Lundin, Ludvig M Sollid
Journal: PLoS Medicine (2004)

Celiac disease is a small intestinal inflammatory disorder characterized by malabsorption, nutrient deficiency, and a range of clinical manifestations. It is caused by an inappropriate immune response to dietary gluten and is treated with a gluten-free diet. Recent feeding studies have indicated oats to be safe for celiac disease patients, and oats are now often included in the celiac disease diet. This study aimed to investigate whether oat intolerance exists in celiac disease and to characterize the cells and processes underlying this intolerance.We selected for study nine adults with celiac disease who had a history of oats exposure. Four of the patients had clinical symptoms on an oats-containing diet, and three of these four patients had intestinal inflammation typical of celiac disease at the time of oats exposure. We established oats-avenin-specific and -reactive intestinal T-cell lines from these three patients, as well as from two other patients who appeared to tolerate oats. The avenin-reactive T-cell lines recognized avenin peptides in the context of HLA-DQ2. These peptides have sequences rich in proline and glutamine residues closely resembling wheat gluten epitopes. Deamidation (glutamine-->glutamic acid conversion) by tissue transglutaminase was involved in the avenin epitope formation.We conclude that some celiac disease patients have avenin-reactive mucosal T-cells that can cause mucosal inflammation. Oat intolerance may be a reason for villous atrophy and inflammation in patients with celiac disease who are eating oats but otherwise are adhering to a strict gluten-free diet. Clinical follow-up of celiac disease patients eating oats is advisable.
Prevention of Coronary Atherosclerosis by Estrogen-Androgen Administration in the Cholesterol-Fed Chick
Authors: JEREMIAH STAMLER, RUTH PICK, LOUIS N. KATZ
Journal: Circulation Research (1953)

Estrogens are highly effective both prophylactically and therapeutically against cholesterol-induced coronary atherogenesis in cockerels. The relative immunity of premenopausal women to coronary sclerosis may be related to the presence of these ovarian hormones. Therefore, estrogens may be useful in the treatment of human coronary atherosclerosis. With this object in mind, the elimination of the feminizing effects of estrogens would be highly desirable. The present experiments prove that concomitant exhibition of androgens and estrogens maintain masculine sex characteristics without interfering with the beneficent effect of estrogens on the coronary arteries in cockerels.
The value of fine-needle-aspiration-biopsy in the diagnosis of acute rejection after liver transplantation
Authors: J. Kwekkeboom, B. Bruyneel, M.L. Kuijf, M. Mass, M. Willems, H.W. Tilanus, P.E. Zondervan, R.A. de Man, H.J. Metselaar
Journal: Journal of Hepatology (2000)
Snail1-Expressing Fibroblasts in the Tumor Microenvironment Display Mechanical Properties That Support Metastasis
Authors: Jelena Stanisavljevic, Jordina Loubat-Casanovas, Mercedes Herrera, Tomás Luque, Raúl Peña, Ana Lluch, Joan Albanell, Félix Bonilla, Ana Rovira, Cristina Peña, Daniel Navajas, Federico Rojo, Antonio García de Herreros, Josep Baulida
Journal: Cancer Research (2014)

Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, two mechanical signals generated through a Snail1/RhoA/αSMA-dependent mechanism that sustains oriented tumor cell migration and invasiveness. Snail1-depleted CAF failed to acquire myofibroblastic traits in response to TGFβ, including RhoA activation, αSMA-positive stress fibers, increased fibronectin fibrillogenesis, and production of a stiff ECM with oriented fibers. Snail1 expression in human tumor-derived CAF was associated with an ability to organize the ECM. In coculture, a relatively smaller number of Snail1-expressing CAF were capable of imposing an anisotropic ECM architecture, compared with nonactivated fibroblasts. Pathologically, human breast cancers with Snail1(+) CAF tended to exhibit desmoplastic areas with anisotropic fibers, lymph node involvement, and poorer outcomes. Snail1 involvement in driving an ordered ECM was further confirmed in wound-healing experiments in mice, with Snail1 depletion preventing the anisotropic organization of granulation tissue and delaying wound healing. Overall, our results showed that inhibiting Snail1 function in CAF could prevent tumor-driven ECM reorganization and cancer invasion.
Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats
Authors: Luis A. Colombato, Agustin Albillos, Roberto J. Groszmann
Journal: Hepatology (1992)

Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by 125 I-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats. Experimental groups were studied from day 1 through day 4 after portial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 ± 0.21 mm Hg · min · ml −1. ·100 gm vs. 5.19 ± 0.16 mm Hg · min · ml −1 100 gm; p &lt;0.01). Plasma volume increased significantly on day 2 (4.31 ± 0.07 ml · 100 gm −1 vs. 3.86 ± 0.04 ml · 100 gm −1 ; p &lt;0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 ± 0.08 ml · 100 gm −1 vs. 3.73 ± 0.03 ml · 100 gm −1 ) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 ± 0.6 ml · min −1. 100 gm −1 vs. 25.5 ± 1.2 ml · min −1 · 100 gm −1 ), iliac and mesenteric blood flow. On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the portal outflow block. Vasodilatation of the superior mesenteric artery bed was delayed until day 4, the time point at which plasma volume is maximally expanded. In portal hypertension, peripheral vasodilatation is the first hemodynamic event in the development of hyperdynamic circulation. Vasodilatation is detectedfirst in the nonsplanchnic circulatory bed and precedes plasma volume expansion, which is then required for the development of the hyperdynamic circulatory state.
Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation
Authors: Jan-Inge Henter, AnnaCarin Samuelsson-Horne, Maurizio Aricò, R Maarten Egeler, Göran Elinder, Alexandra H Filipovich, Helmut Gadner, Shinsaku Imashuku, Diane Komp, Stephan Ladisch, David Webb, Gritta Janka
Journal: Blood (2002)
The Efficiency of CD4 Recruitment to Ligand-engaged TCR Controls the Agonist/Partial Agonist Properties of Peptide–MHC Molecule Ligands
Authors: Joaquín Madrenas, Luan A. Chau, Judy Smith, Jeffrey A. Bluestone, Ronald N. Germain
Journal: The Journal of Experimental Medicine (1997)

One hypothesis seeking to explain the signaling and biological properties of T cell receptor for antigen (TCR) partial agonists and antagonists is the coreceptor density/kinetic model, which proposes that the pharmacologic behavior of a TCR ligand is largely determined by the relative rates of (a) dissociation of ligand from an engaged TCR and (b) recruitment of lck-linked coreceptors to this ligand-engaged receptor. Using several approaches to prevent or reduce the association of CD4 with occupied TCR, we demonstrate that consistent with this hypothesis, the biological and biochemical consequence of limiting this interaction is to convert typical agonists into partial agonist stimuli. Thus, adding anti-CD4 antibody to T cells recognizing a wild-type peptide–MHC class II ligand leads to disproportionate inhibition of interleukin-2 (IL-2) relative to IL-3 production, the same pattern seen using a TCR partial agonist/antagonist. In addition, T cells exposed to wild-type ligand in the presence of anti-CD4 antibodies show a pattern of TCR signaling resembling that seen using partial agonists, with predominant accumulation of the p21 tyrosine-phosphorylated form of TCR-ζ, reduced tyrosine phosphorylation of CD3ε, and no detectable phosphorylation of ZAP-70. Similar results are obtained when the wild-type ligand is presented by mutant class II MHC molecules unable to bind CD4. Likewise, antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like pattern. Finally, in accord with data showing that partial agonists often induce T cell anergy, CD4 blockade during antigen exposure renders cloned T cells unable to produce IL-2 upon restimulation. These results demonstrate that the biochemical and functional responses to variant TCR ligands with partial agonist properties can be largely reproduced by inhibiting recruitment of CD4 to a TCR binding a wild-type ligand, consistent with the idea that the relative rates of TCR–ligand disengagement and of association of engaged TCR with CD4 may play a key role in determining the pharmacologic properties of peptide–MHC molecule ligands. Beyond this insight into signaling through the TCR, these results have implications for models of thymocyte selection and the use of anti-coreceptor antibodies in vivo for the establishment of immunological tolerance.
Lovastatin (Mevinolin) in the Treatment of Heterozygous Familial Hypercholesterolemia
Authors: RICHARD J. HAVEL
Journal: Annals of Internal Medicine (1987)

Study Objective: To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia. Design: Randomized, double-blind, placebo-controlled, multicenter trial. Setting: Five lipid clinics with a central laboratory and coordinating center. Patients: 101 adult patients with heterozygous familial hypercholesterolemia. Interventions: Patients were on a lipid-lowering diet throughout the study. After a 4-week placebo baseline period, patients were randomized to five equal treatment groups. Each group received a different sequence of placebo or lovastatin 5 to 40 mg twice daily or 20 to 40 mg once daily in the evening, during three consecutive 6-week periods. Measurements and Main Results: The mean reductions in total plasma cholesterol and low-density lipoprotein cholesterol across the dosage ranges were 14% to 34% and 17% to 39%, respectively (p compared with zero and placebo < 0.01). High-density lipoprotein cholesterol and apolipoproteins Al and All rose slightly. Apolipoprotein B fell substantially at the higher dosage levels (-23% at 40 mg twice daily, p < 0.01), indicating a reduction in the concentration of circulating low-density lipoprotein particles. Maximum response was achieved in 4 to 6 weeks. Twice-daily dosing was slightly more efficient than once-daily dosing. Of those patients receiving 40 mg twice a day, 89% had a fall in low-density lipoprotein cholesterol of at least 20%, and 61% had a fall of at least 40%. Adverse effects attributable to lovastatin were minimal, and no patient was withdrawn from the study. Conclusion: Lovastatin was well tolerated and effective in the treatment of familial hypercholesterolemia.
Applying the 2011 St Gallen panel of prognostic markers on a large single hospital cohort of consecutively treated primary operable breast cancers
Authors: O. Brouckaert, A. Laenen, J. Vanderhaegen, H. Wildiers, K. Leunen, F. Amant, P. Berteloot, A. Smeets, R. Paridaens, M.R. Christiaens, G. Floris, P. Moerman, E. Van Limbergen, S. Peeters, C. Weltens, I. Vergote, P. Neven
Journal: Annals of Oncology (2012)
Evidence-Based Treatment of Post-Traumatic Stress Disorder
Authors: JoAnn Difede, Megan Olden, Judith Cukor
Journal: Annual Review of Medicine (2014)

The term translational research is typically used to refer both to “bench to bedside” research, in which preclinical research findings inform the development of novel therapeutics, and to the dissemination of new treatments to the community to encourage the use of the new health practices and treatments. Both definitions are germane to understanding the evidence base for treatment of post-traumatic stress disorder (PTSD) today. This article offers (a) an overview of evidence-based treatments for PTSD, (b) a description of a translational model of PTSD, and (c) a discussion of common barriers to dissemination and implementation of the empirically validated treatments. Recent studies in the field are discussed with a focus on pharmacotherapies, psychotherapies, and combined treatments.
Rhabdomyolysis After Ingestion of an Appetite Suppressant
Authors: K. Wolfgang Rumpf
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Recently, Swenson et al (1982;248:1216) reported on two patients with acute rhabdomyolysis and renal failure after the ingestion of diet pills containing phenylpropanolamine hydrochloride. The authors suggest a causal role of this agent in the development of nontraumatic rhabdomyolysis, although they admit that because of complicating features in their cases, definitive proof is lacking. We had the opportunity to observe a similar patient who had taken an overdose of the appetite suppressant cathine hydrochloride (formerly D-norpseudoephedrine), one of the isomers of phenylpropanolamine. We think that our case adds further evievi- for a causal relationship between sympathomimetic appetite suppressants and rhabdomyolysis. This seems to be especially plausible, since other similar amphetaminelike drugs<sup>1-3</sup>and the appetite suppressant fenfluramine hydrochloride<sup>4</sup>have been implicated in the pathogenesis of rhabdomyolysis. <h3>Report of a Case.—</h3> A 46-year-old man without previous medical history who is a member of an antialcohol society had
Functional TRPM7 Channels Accumulate at the Plasma Membrane in Response to Fluid Flow
Authors: Elena Oancea, Joshua T. Wolfe, David E. Clapham
Journal: Circulation Research (2005)

Many cells are constantly exposed to fluid mechanical forces generated by flowing blood, and wall shear stresses modulate aspects of their structure and function. However, the mechanisms for mechanotransduction of flow are not well understood. Here we report that TRPM7, which is both an ion channel and a functional kinase, is translocated within cells in response to laminar flow. After exposure of cells to physiological values of laminar fluid flow, the number of TRPM7 molecules localized at or near the plasma membrane increased up to 2-fold, in less than 100 seconds. This increase in membrane-localized GFP-TRPM7, as seen by total internal reflection fluorescence microscopy, closely correlated with increases in TRPM7 current. Both endogenous and heterologously expressed TRPM7 was found in tubulovesicular structures that were translocated to the region of the plasma membrane on induction of shear stress. In vascular smooth muscle cells, but not in several types of endothelial cells, fluid flow increased endogenous native TRPM7 current amplitude. We hypothesize that TRPM7 plays a role in pathological response to vessel wall injury.
Dendritic cells but not B cells present antigenic complexes to class II-restricted T cells after administration of protein in adjuvant.
Authors: J C Guéry, F Ria, L Adorini
Journal: The Journal of Experimental Medicine (1996)

We have analyzed the relative contribution of dendritic cells (DC) and B cells in the presentation of peptide-class II complexes in an inflammatory situation in vivo. Draining lymph node cells from mice immunized subcutaneously with hen egg-white lysozyme (HEL) in adjuvant display HEL peptide-major histocompatibility complex class II complexes able to stimulate, in the absence of any further antigen addition, specific T hybridoma cells. The antigen-presenting capacity of three different antigen-presenting cell (APC) populations recruited in lymph nodes, DC (N418+, class II+, B220-, low buoyant density), large B cells (B220+, low buoyant density), and small B cells (B220+, high buoyant density), was analyzed. After immunization with HEL in adjuvant, DC are the only lymph node APC population expressing detectable HEL peptide-class II complexes. These results indicate that lymph node DC and not B cells are the APC initiating the immune response in vivo after administration of antigen in adjuvant.