tbuckley/cabot-search huggingface dataset:
The Wine of Generations
Authors: B. A. St. Andrews
Journal: JAMA (2002)

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Optical Nanoscopy: From Acquisition to Analysis
Authors: Travis J. Gould, Samuel T. Hess, Joerg Bewersdorf
Journal: Annual Review of Biomedical Engineering (2012)

Recent advances in far-field microscopy have demonstrated that fluorescence imaging is possible at resolutions well below the long-standing diffraction limit. By exploiting photophysical properties of fluorescent probe molecules, this new class of methods yields a resolving power that is fundamentally diffraction unlimited. Although these methods are becoming more widely used in biological imaging, they must be complemented by suitable data analysis approaches if their potential is to be fully realized. Here we review the basic principles of diffraction-unlimited microscopy and how these principles influence the selection of available algorithms for data analysis. Furthermore, we provide an overview of existing analysis strategies and discuss their application.
Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents
Authors: Laura Mauri, Dean J. Kereiakes, Robert W. Yeh, Priscilla Driscoll-Shempp, Donald E. Cutlip, P. Gabriel Steg, Sharon-Lise T. Normand, Eugene Braunwald, Stephen D. Wiviott, David J. Cohen, David R. Holmes, Mitchell W. Krucoff, James Hermiller, Harold L. Dauerman, Daniel I. Simon, David E. Kandzari, Kirk N. Garratt, David P. Lee, Thomas K. Pow, Peter Ver Lee, Michael J. Rinaldi, Joseph M. Massaro
Journal: New England Journal of Medicine (2014)

Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain.Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding.A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment.Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).
Tumor Necrosis Factor α and Adiponectin in Bone Marrow Interstitial Fluid from Patients with Acute Myeloid Leukemia Inhibit Normal Hematopoiesis
Authors: Per Ole Iversen, Helge Wiig
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Locally residing cytokines may inhibit bone marrow hematopoiesis in acute myeloid leukemia (AML). Using a novel method to isolate bone marrow interstitial fluid, we examined if this fluid from 10 adult AML patients could affect normal bone marrow hematopoiesis. Experimental Design: Bone marrow interstitial fluid was isolated by centrifugation of bone marrow biopsies obtained at time of diagnosis and 2 to 4 weeks after start of induction therapy. The isolated fluid was added to normal bone marrow CD34 hematopoietic progenitor cells sampled from five healthy subjects. Results: Unlike plasma, AML-derived bone marrow interstitial fluid clearly repressed hematopoietic progenitor cell growth as determined by an in vitro colony assay, an effect that was lost after successful induction treatment. Antibodies against tumor necrosis factor α (TNFα) and adiponectin abolished growth inhibition by bone marrow interstitial fluid, suggesting a mechanistic role of these cytokines in impairing normal hematopoiesis in AML. The plasma levels of adiponectin and TNFα were unaffected by therapy whereas bone marrow interstitial fluid levels of both cytokines fell significantly in patients entering remission. Transcripts for TNFα, but not for adiponectin, were found in AML blast cells. Neither the plasma levels nor the bone marrow interstitial fluid levels of the proangiogenic factors vascular endothelial growth factor or basic fibroblast growth factor were appreciably elevated in the patients nor did they change with treatment. Conclusions: Specific analyses of bone marrow interstitial fluid may give novel information on normal and malignant hematopoietic activity and thus form the basis for mechanism-based therapy.
The myocardial no-reflow phenomenon: Role of δPKC
Authors: Gregory J. Wilson, Roberto J. Diaz
Journal: Cardiovascular Research (2007)

See article by Ikeno et al.  [1]  (pages 699–709) in this issue. 

In the paper “Impaired perfusion after myocardial infarction is due to reperfusion-induced δPKC-mediated myocardial damage” by Ikeno et al. [1], Dr. Daria Mochly-Rosen's group at Stanford University have demonstrated a novel molecular interventional strategy, targeted inhibition of the δ isoform of protein kinase C (δPKC), to treat the post-ischemic no-reflow phenomenon in the myocardium using both mouse and pig models. This they achieved by either expressing a δPKC-specific translocation inhibitor protein fragment, δV1-1, only in cardiomyocytes in a transgenic crystalloid perfused mouse ex-vivo acute global myocardial ischemia (30 min)/reperfusion (120 min) model or through intra-coronary delivery of the TAT-conjugated synthetic peptide δV1-1 during the last minute of ischemia in a porcine in-vivo regional (LAD) myocardial ischemia (30 min)/reperfusion (30 min, 24 h, 6 and 12 days) model.

Their mouse experiments showed a roughly 70% reduction in both infarction and coronary vascular resistance 5 min after reflow compared to wild-type hearts. Direct coronary delivery of the δV1-1 peptide in wild-type hearts provided similar results and, when added to the δV1-1 transgenic hearts, essentially eliminated the rise in coronary vascular resistance although no further reduction in muscle necrosis was achieved. These results suggest that δPKC inhibition protects both cardiomyocytes and microvasculature, as indicated by these investigators [1].

Their pig model included the contribution of blood cells and energy demand on the in vivo ischemic heart and involved regional ischemia more closely mimicking the clinical setting of reperfusion therapy in acute myocardial infarction. The δV1-1 peptide intra-coronary infusion performed as … 

*Corresponding author. Division of Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8. Tel.: +1 416 813 2095; fax: +1 416 813 5965. Email address: gregory.wilson{at}sickkids.ca
Risk factors for sports injuries — a methodological approach
Authors: R Bahr, I Holme
Journal: British Journal of Sports Medicine (2003)

The methodology for studies designed to investigate potential risk factors for sports injury is reviewed, using the case of hamstring strains as an example. Injuries result from a complex interaction of multiple risk factors and events. Therefore, a multivariate statistical approach should be used. In addition, the sample size of the study needs to be considered carefully. Sample size mainly depends on the expected effect of the risk factor on injury risk, and to detect moderate to strong associations 20–50 injury cases are needed, whereas small to moderate associations would need about 200 injured subjects. Studies published to date on the risk factors for hamstring strains have methodological limitations, and are too small to detect small to moderate associations.
Cardiac gap junctions and gap junction-associated vesicles: ultrastructural comparison of in situ negative staining with conventional positive staining.
Authors: L Chen, G E Goings, J Upshaw-Earley, E Page
Journal: Circulation Research (1989)

By comparing in situ negative staining of mammalian heart muscle using La(NO3)3 with conventional positive staining by uranium and lead salts, we showed that 1) the membrane area of rat cardiac gap junctions (GJs) at the intercalated disks is threefold to fourfold greater than previously thought; 2) connexon arrays of cardiac GJ are subdivided into microdomains by connexon-free aisles; 3) profiles of GJ-associated vesicles (GJAVs) of plasmalemmal origin (which are present extracellularly and sharply localized at three extracellular sites) are paired to form GJs with each other and with myocyte plasmalemma; 4) some GJAVs contain arrays of assembled connexons; and 5) myocytes contain intracytoplasmic complexes lying within cylindrical or cigar-shaped membranes and consisting of GJs and multiple vesicles apparently dissociating from these GJs.
Neoadjuvant Clinical Trial With Sorafenib for Patients With Stage II or Higher Renal Cell Carcinoma
Authors: C. Lance Cowey, Chirag Amin, Raj S. Pruthi, Eric M. Wallen, Matthew E. Nielsen, Gayle Grigson, Cathy Watkins, Keith V. Nance, Jeffrey Crane, Mark Jalkut, Dominic T. Moore, William Y. Kim, Paul A. Godley, Young E. Whang, Julia R. Fielding, W. Kimryn Rathmell
Journal: Journal of Clinical Oncology (2010)

The multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting.Thirty patients with clinical stage II or higher renal masses, selected based on their candidacy for nephrectomy, underwent preoperative treatment with sorafenib. Toxicities, surgical complications, and tumor responses were monitored.Of the thirty patients enrolled, 17 patients had localized disease and 13 had metastatic disease. After a course of sorafenib therapy (median duration, 33 days), a decrease in primary tumor size (median, 9.6%) and radiographic evidence of loss of intratumoral enhancement, quantified using a methodology similar to Choi criteria (median, 13%), was also observed. According to Response Evaluation Criteria in Solid Tumors, of the 28 patients evaluable for response, two patients had a partial response and 26 had stable disease, with no patients progressing on therapy. Toxicities from sorafenib were similar to that expected with this class of medication. All patients were able to proceed with nephrectomy and no surgical complications related to sorafenib administration were observed.The administration of preoperative sorafenib therapy can impact the size and density of the primary tumor and appears safe and feasible. Further studies are required to determine if preoperative systemic therapy improves outcomes in patients undergoing nephrectomy for renal cell carcinoma.
Polymorphism of interleukin-1β affects the eradication rates of Helicobacter pylori by triple therapy
Authors: Takahisa Furuta, Naohito Shirai, Fang Xiao, Emad M. El-omar, Charles S. Rabkin, Haruhiko Sugimura, Takashi Ishizaki, Kyoichi Ohashi
Journal: Clinical Gastroenterology and Hepatology (2004)
Self-perpetuating mechanisms of immunoglobulin G aggregation in rheumatoid inflammation.
Authors: J Lunec, D R Blake, S J McCleary, S Brailsford, P A Bacon
Journal: Journal of Clinical Investigation (1985)

When human IgG is exposed to free radical generating systems such as ultraviolet irradiation, peroxidizing lipids, or activated human neutrophils, characteristic auto-fluorescent monomeric and polymeric IgG is formed (excitation [Ex], 360 nm, emission [Em], 454 nm). 1 h ultraviolet irradiation of IgG results in the following reductions in constituent amino acids; cysteine (37.0%), tryptophan (17.0%), tyrosine (10.5%), and lysine (3.6%). The fluorescent IgG complexes, when produced in vitro, can stimulate the release of superoxide from normal human neutrophils. In the presence of excess unaltered IgG, further fluorescent damage to IgG occurs. Measurement and isolation of fluorescent monomeric and polymeric IgG by high performance liquid chromatography, from in vitro systems and from fresh rheumatoid sera and synovial fluid, indicates that identical complexes are present in vivo; all these fluorescent complexes share the property of enhancing free radical production from neutrophils. The results described in this study support the hypothesis that fluorescent monomeric and aggregated IgG may be formed in vivo by oxygen-centered free radicals derived from neutrophils, and that in rheumatoid inflammation this reaction may be self-perpetuating within the inflamed joint.
Cranial Irradiation Alters the Behaviorally Induced Immediate-Early Gene <i>Arc</i> (Activity-Regulated Cytoskeleton-Associated Protein)
Authors: Susanna Rosi, Marta Andres-Mach, Kelly M. Fishman, William Levy, Ryan A. Ferguson, John R. Fike
Journal: Cancer Research (2008)

Abstract Therapeutic irradiation of the brain is commonly used to treat brain tumors but can induce cognitive impairments that can severely affect quality of life. The underlying mechanisms responsible for radiation-induced cognitive deficits are unknown but likely involve alterations in neuronal activity. To gain some mechanistic insight into how irradiation may affect hippocampal neurons known to be associated with cognitive function, we quantitatively assessed the molecular distribution of the behaviorally induced immediate-early gene Arc (activity-regulated cytoskeleton-associated protein) at the level of mRNA and the protein. Young adult C57BL/6J mice received whole-brain irradiation with 0 or 10 Gy, and 1 week or 2 months later, exploration of a novel environment was used to induce Arc expression. The fractions of neurons expressing Arc mRNA and Arc protein were detected using fluorescence in situ hybridization and immunocytochemistry, respectively. Our results showed that there was a significant reduction in the percentage of neurons expressing Arc protein 1 week after irradiation, whereas 2 months after irradiation, there was a reduction in the percentage of neurons expressing both Arc mRNA and Arc protein. Importantly, radiation-induced changes in Arc expression were not a result of neuronal cell loss. The changes observed at 2 months were associated with a significant increase in the number of activated microglia, supporting the idea that inflammation may contribute to neuronal dysfunction. These findings are the first to show that local brain irradiation initiates changes in hippocampal neurons that disrupt the activity patterns (Arc expression) associated with neuroplasticity and memory. [Cancer Res 2008;68(23):9763–70]
Staff-Patient Staff Conferences
Authors: ERIC BERNE
Journal: American Journal of Psychiatry (1968)

The author describes a procedure whereby, following a ward meeting or group therapy session, the staff holds its professional conference—including treatment planning—in the presence of the patients. If certain rules (which he lists) are followed and each member of the staff speaks frankly and to the point, patients of all ages and diagnostic categories are almost unanimously appreciative. A few staff members find this procedure distasteful while others find it congenial, stimulating, and therapeutically valuable.
Collagen-binding integrin α1β1 regulates intestinal inflammation in experimental colitis
Authors: Christian F. Krieglstein, Wolfgang H. Cerwinka, Andrew G. Sprague, F. Stephen Laroux, Matthew B. Grisham, Victor E. Koteliansky, Norbert Senninger, D. Neil Granger, Antonin R. de Fougerolles
Journal: Journal of Clinical Investigation (2002)

Central to inflammatory responses are the integrin-mediated adhesive interactions of cells with their ECM-rich environment. We investigated the role of the collagen-binding integrin α1β1 in intestinal inflammation using the mouse model of colitis induced by dextran sodium sulfate (DSS). mAb’s directed against murine α1 were found to significantly attenuate inflammation and injury in DSS-treated wild-type mice; similar protection was seen in mice deficient for α1β1 integrin. Blockade or loss of α1β1 was also associated with decreased mucosal inflammatory cell infiltrate and cytokine production. Importantly, we demonstrated that development and α1-mediated inhibition of DSS-induced colitis occurred independently of lymphocytes (Rag-2–/– mice), and identified the monocyte as a key α1β1-expressing cell type involved in the development of colitis in this model. In response to DSS, both α1 deficiency and anti-α1 mAb treatment significantly reduced monocyte accumulation and activation within the lamina propria. In summary, the data demonstrate that engagement of leukocyte-associated α1β1 receptors with ECM plays a pivotal role in mediating intestinal inflammation via promotion of monocyte movement and/or activation within the inflamed interstitium. Therapeutic strategies designed to disrupt such interactions may prove beneficial in treating intestinal inflammation.
Thrombin-induced expression of RANTES mRNA through protease activated receptor-1 in human synovial fibroblasts
Authors: F Hirano
Journal: Annals of the Rheumatic Diseases (2002)

<h3>Objective</h3> To assess resting cerebral blood flow (CBF) in the whole brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. <h3>Methods</h3> This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. <h3>Results</h3> The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78–31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08–24.70) for healthy controls, <i>p</i> = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72–27.12] vs 16.25 mL/100 mL/min [95% CI 14.03–18.48], <i>p</i> = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85–43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57–42.35], <i>p</i> = 0.38). In patients with FD with WMH (n = 20), whole brain CBF correlated with WMH volume (<i>r</i> = 0.59, <i>p</i> = 0.006), not with plasma lyso-Gb3. <h3>Conclusion</h3> In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury.
Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study
Authors: Caroline Oudot, Marie-Françoise Auclerc, Vincent Levy, Raphaël Porcher, Christophe Piguet, Yves Perel, Virginie Gandemer, Marianne Debre, Christiane Vermylen, Brigitte Pautard, Claire Berger, Claudine Schmitt, Thierry Leblanc, Jean-Michel Cayuela, Gérard Socie, Gérard Michel, Guy Leverger, André Baruchel
Journal: Journal of Clinical Oncology (2008)

To identify prognostic factors and to evaluate the outcome of children with acute lymphoblastic leukemia (ALL) failure after induction therapy.Between June 1993 and December 1999, 1,395 leukemic children were included in the French Acute Lymphoblastic Leukemia 93 study.Fifty-three patients (3.8%) had a leukemic induction failure (LIF) after three- or four-drug induction therapy. In univariate analysis, high WBC count (P = .001), mediastinal mass (P = .017), T-cell phenotype (T-ALL; P = .001), t(9;22) translocation (P = .001), and a slow early response (at day 8 and/or on day 21, P = .001) were predictive of LIF. The following three prognostic groups for LIF were identified by multivariate analysis: a low-risk group with B-cell progenitor (BCP) ALL without t(9;22) (odds ratio [OR] = 1), an intermediate-risk group with T-ALL and a mediastinal mass (OR = 7.4, P < .0001), and a high-risk group with BCP-ALL and t(9;22) or T-ALL without a mediastinal mass (OR = 28.4, P < .0001). Complete remission (CR) was subsequently obtained in 43 patients (81%). The 5-year overall survival (OS) rate of the 53 patients was 30% +/- 6%. The 5-year OS rate among allogeneic graft recipients, autologous graft recipients, and after chemotherapy were 30.4% +/- 9.6% (50% +/- 26% after genoidentical transplantation), 50% +/- 17.7%, and 41.7% +/- 14.2%, respectively (P = .18). Fourteen patients (26%) were still in first CR after a median of 83 months (range, 53 to 117 months).Three risk categories for LIF in children with ALL were identified. Approximately one third of patients with LIF can be successfully treated with salvage therapy overall. Subsequent CR after LIF is mandatory for cure.