tbuckley/cabot-search huggingface dataset:
Initial care and outcome of glioblastoma multiforme patients in 2 diverse health care scenarios in Brazil: does public versus private health care matter?
Authors: L. V. M. Loureiro, L. d. B. Pontes, D. Callegaro-Filho, L. d. O. Koch, E. Weltman, E. d. S. Victor, A. J. Santos, L. R. R. Borges, R. A. Segreto, S. M. F. Malheiros
Journal: Neuro-Oncology (2014)

The aim of this study was to describe the epidemiological and survival features of patients with glioblastoma multiforme treated in 2 health care scenarios—public and private—in Brazil. We retrospectively analyzed clinical, treatment, and outcome characteristics of glioblastoma multiforme patients from 2003 to 2011 at 2 institutions. The median age of the 171 patients (117 public and 54 private) was 59.3 years (range, 18–84). The median survival for patients treated in private institutions was 17.4 months (95% confidence interval, 11.1–23.7) compared with 7.1 months (95% confidence interval, 3.8–10.4) for patients treated in public institutions (P < .001). The time from the first symptom to surgery was longer in the public setting (median of 64 days for the public hospital and 31 days for the private institution; P = .003). The patients at the private hospital received radiotherapy concurrent with chemotherapy in 59.3% of cases; at the public hospital, only 21.4% (P < .001). Despite these differences, the institution of treatment was not found to be an independent predictor of outcome (hazard ratio, 1.675; 95% confidence interval, 0.951–2.949; P = .074). The Karnofsky performance status and any additional treatment after surgery were predictors of survival. A hazard ratio of 0.010 (95% confidence interval, 0.003–0.033; P < .001) was observed for gross total tumor resection followed by radiotherapy concurrent with chemotherapy. Despite obvious disparities between the hospitals, the medical assistance scenario was not an independent predictor of survival. However, survival was directly influenced by additional treatment after surgery. Therefore, increasing access to resources in developing countries like Brazil is critical.
Pulmonary artery thrombosis and the nephrotic syndrome.
Authors: I. S. Menon
Journal: BMJ (1967)

MEDIALJOUHHow much easier it would be if platelet stickiness were expressed as the percentage of sticky platelets rather than as the percentage of non-sticky platelets, and how much more logical.That is: Platelet stickiness (%)= (Original Count minus Second Count) x 100Original Count With this simple transformation a high value would indicate a high degree of stickiness, and the need for mathematical gym- nastics from the reader would disappear.I would have thought that this subject is still sufficiently young to allow this break with tradition in the interests of simplicity.-I am, etc.,
Survival Differences Following Lung Transplantation Among US Transplant Centers
Authors: Gabriel Thabut, Jason D. Christie, Walter K. Kremers, Michel Fournier, Scott D. Halpern
Journal: JAMA (2010)

Although case loads vary substantially among US lung transplant centers, the impact of center effects on patient outcomes following lung transplantation is unknown.To assess variability in long-term survival following lung transplantation among US lung transplant centers.Analysis of data from the United Network for Organ Sharing registry for 15,642 adult patients undergoing lung transplantation between 1987 and 2009 in 61 US transplantation centers still active in 2008.Mixed-effect Cox models were fitted to assess survival following lung transplantation at individual centers.In 2008, 19 centers (31.1%) performed between 1 and 10 lung transplantations; 18 centers (29.5%), from 11 to 25 transplantations; 20 centers (32.8%), from 26 to 50 transplantations; and 4 centers (6.6%), more than 50 transplantations. One-month, 1-year, 3-year, and 5-year survival rates among all 61 centers were 93.4% (95% confidence interval [CI], 93.0% to 93.8%), 79.7% (95% CI, 79.1% to 80.4%), 63.0% (95% CI, 62.2% to 63.8%), and 49.5% (95% CI, 48.6% to 50.5%), respectively. Characteristics of donors, recipients, and surgical techniques varied substantially among centers. After adjustment for these factors, marked variability remained among centers, with hazard ratios for death ranging from 0.70 (95% CI, 0.59 to 0.82) to 1.71 (95% CI, 1.36 to 2.14) for low- vs high-risk centers, for 5-year survival rates of 30.0% to 61.1%. Higher lung transplantation volumes were associated with improved long-term survival and accounted for 15% of among-center variability; however, variability in center performance remained significant after controlling for procedural volume (P < .001).Center-specific variation in survival following lung transplantation was only partly associated with procedural volume. However, other statistically significant sources of variability remain to be identified.
The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)
Authors: Asha L. Bhakar, Gül Dölen, Mark F. Bear
Journal: Annual Review of Neuroscience (2012)

Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way.
Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials
Authors: Nicolas Boissel, Marie-Françoise Auclerc, Véronique Lhéritier, Yves Perel, Xavier Thomas, Thierry Leblanc, Philippe Rousselot, Jean-Michel Cayuela, Jean Gabert, Nathalie Fegueux, Christophe Piguet, Françoise Huguet-Rigal, Christian Berthou, Jean-Michel Boiron, Cécile Pautas, Gérard Michel, Denis Fière, Guy Leverger, Hervé Dombret, André Baruchel
Journal: Journal of Clinical Oncology (2003)

Purpose: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. Patients and Methods: From June 1993 to September 1994, 77 and 100 adolescents (15 to 20 years of age) were enrolled in the pediatric FRALLE-93 and adult LALA-94 protocols, respectively. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving complete remission (CR) and event-free survival (EFS). Results: Patients were younger in the FRALLE-93 than in the LALA-94 protocol (median age, 15.9 v 17.9 years, respectively), but other characteristics were similar, including median WBC count (18 × 10 9 cells/L v 16 × 10 9 cells/L), B/T-lineage (54 of 23 v 72 of 28 patients), CD10-negative ALL (13% v 15%), and poor-risk cytogenetics (t(9;22), t(4;11), or hypodiploidy less than 45 chromosomes: 6% v 5%). The CR rate depended on WBC count (P = .005) and trial (94% v 83% in FRALLE-93 and LALA-94, respectively; P = .04). Univariate analysis showed that unfavorable prognostic factors for EFS were as follows: the trial (estimated 5-year EFS, 67% v 41% for FRALLE-93 and LALA-94, respectively; P &lt; .0001), an increasing WBC count (P &lt; .0001), poor-risk cytogenetics (P = .005), and T-lineage (P = .01). The trial and WBC count remained significant parameters for EFS in multivariate analysis (P &lt; .0001 and P = .0004). Lineage subgroup analysis showed an advantage for the FRALLE-93 trial for CR achievement (98% v 81%; P = .002) and EFS (P = .0002) in B-lineage ALL and for EFS (P = .05) in T-lineage ALL. Age was not a significant prognostic factor in this population of adolescents. Conclusion: This study’s findings indicate that adolescents should be included in intensive pediatric protocols and that new trials should be designed, inspired by pediatric protocols, for the treatment of young adults with ALL.
Henoch Schonlein purpura in children: an epidemiological study among Dutch paediatricians on incidence and diagnostic criteria
Authors: J. Aalberse, K. Dolman, G. Ramnath, R. R. Pereira, J.-C. Davin
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Background:</h3> The aim of the present study on the occurrence of Henoch–Schönlein Purpura (HSP) in Dutch children is to give some insight into the epidemiology of HSP in the Netherlands, to record the diagnostic criteria used by Dutch paediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are available. <h3>Methods:</h3> Each month in 2004, all Dutch paediatricians received an electronic card asking them to mention new diagnosed HSP. Paediatricians reporting one or more new patients with HSP were sent a list of questions concerning various parameters. <h3>Results:</h3> 232 patients from 0 to 18 years of age (6.1/10<sup>5</sup>) were reported as having contracted HSP in 2004. 29% presented renal symptoms. In accordance with the classification criteria of the American College of Rheumatology, 80% of paediatricians consider that isolated purpura (without haematological abnormalities) is sufficient to allow the diagnosis of HSP in children. From the 17 skin biopsies performed, only 9 (53%) presented IgA deposits. The follow-up duration, considered as necessary, was longer in case of renal symptoms at presentation. However, 45% of patients without renal symptoms would be followed for more than 1 year. <h3>Conclusion:</h3> Considering the recent (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides, HSP should have been diagnosed in only 160 of the 179 patients of our study. The use of isolated non-thrombocytopenic purpura as the only criterion to diagnose HSP in children might therefore lead to over diagnosis and unnecessary follow-up.
A 3′ Enhancer Controls Snail Expression in Melanoma Cells
Authors: Matthew B. Palmer, Parimal Majumder, Myesha R. Green, Paul A. Wade, Jeremy M. Boss
Journal: Cancer Research (2007)

Abstract The snail gene encodes a transcriptional repressor that functions during animal development and in cancer progression to promote epithelial-mesenchymal transitions. Strict spatial and temporal boundaries of Snail expression in development imply precise transcriptional control, which becomes inappropriately activated in many cancer subtypes. To gain insight into the molecular mechanism(s) governing transcriptional control of Snail, we analyze chromatin structural changes associated with Snail transcription in melanoma cells. Regardless of transcriptional status, the Snail promoter displays three constitutive DNase hypersensitive sites (HS) and a moderate level of histone H3 Lys4 dimethylation. A robust HS is found in the 3′ region of A375 melanoma cells, in which Snail is highly expressed, but is absent in cells not expressing Snail. This element is conserved throughout the mammalian lineage and strongly activates expression of a reporter in A375 and Colo829 melanoma cells, but not in keratinocytes or primary melanocytes. Activity of this enhancer is associated with enrichment of H3 Lys4 dimethylation and H3 acetylation at both the enhancer and the promoter. Additionally, enhancer activity is associated with H3 Lys4 trimethylation at the promoter. A physical interaction between the 3′ enhancer and promoter was observed in Snail-expressing cells, demonstrating a direct role for the enhancer in Snail expression. These results suggest a model in which the Snail promoter is constitutively packaged in a poised chromatin structure that can be activated in melanoma cells by a tissue-specific enhancer, which physically contacts the promoter. [Cancer Res 2007;67(13):6113–20]
C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function
Authors: Subodh Verma, Michael A. Kuliszewski, Shu-Hong Li, Paul E. Szmitko, Liana Zucco, Chao-Hung Wang, Mitesh V. Badiwala, Donald A.G. Mickle, Richard D. Weisel, Paul W.M. Fedak, Duncan J. Stewart, Michael J.B. Kutryk
Journal: Circulation (2004)

Myocardial ischemia provides a potent stimulus to angiogenesis, and the mobilization and differentiation of endothelial progenitor cells (EPCs) has been shown to be important in this process. An elevated level of C-reactive protein (CRP) has emerged as one of the most powerful predictors of cardiovascular disease. However, the impact of CRP on EPC biology is unknown.EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in endothelial cell basal medium-2 in the absence and presence of CRP (5 to 20 microg/mL), rosiglitazone (1 micromol/L), and/or vascular endothelial growth factor. EPC differentiation, survival, and function were assayed. CRP at concentrations > or =15 microg/mL significantly reduced EPC cell number, inhibited the expression of the endothelial cell-specific markers Tie-2, EC-lectin, and VE-cadherin, significantly increased EPC apoptosis, and impaired EPC-induced angiogenesis. EPC-induced angiogenesis was dependent on the presence of nitric oxide, and CRP treatment caused a decrease in endothelial nitric oxide synthase mRNA expression by EPCs. However, all of these detrimental CRP-mediated effects on EPCs were attenuated by pretreatment with rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist.Human recombinant CRP, at concentrations known to predict adverse vascular outcomes, directly inhibits EPC differentiation, survival, and function, key components of angiogenesis and the response to chronic ischemia. This occurs in part via an effect of CRP to reduce EPC eNOS expression. The PPARgamma agonist rosiglitazone inhibits the negative effects of CRP on EPC biology. The ability of CRP to inhibit EPC differentiation and survival may represent an important mechanism that further links inflammation to cardiovascular disease.
Prediction of Protein-Protein Interactions Using Protein Signature Profiling
Authors: Mahmood A. Mahdavi, Yen-Han Lin
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain interactions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as “interacting”. In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area under the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs increased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on average 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.
Cocaine Stimulates the Human Cardiovascular System via a Central Mechanism of Action
Authors: Wanpen Vongpatanasin, Yasser Mansour, Bahman Chavoshan, Debbie Arbique, Ronald G. Victor
Journal: Circulation (1999)

Background —Cocaine is thought to stimulate the cardiovascular system by blocking peripheral norepinephrine reuptake. This study was designed to test the novel hypotheses that cocaine also stimulates the human cardiovascular system by (1) increasing central sympathetic outflow, or (2) decreasing parasympathetic control of heart rate. Methods and Results —In 14 healthy cocaine-naive humans, we measured blood pressure, heart rate, and skin sympathetic nerve activity (SNA) with intraneural microelectrodes before, during, and for 90 minutes after intranasal cocaine (2 mg/kg, n=7) or lidocaine (2 mg/kg, n=7). Intranasal cocaine caused an initial but transient 3.3-fold increase in skin SNA during the period of intranasal administration followed by a sustained 2.4-fold increase lasting for up to 90 minutes after cocaine. Unlike cocaine, intranasal lidocaine caused only a small transient increase in skin SNA due to local nasal irritation. The cocaine-induced increase in SNA was accompanied by decreased skin blood flow, increased skin vascular resistance, and increased heart rate. In 11 additional subjects, we showed that the cocaine-induced increase in heart rate was eliminated by β-adrenergic receptor blockade (propranolol) but unaffected by muscarinic receptor blockade (atropine), indicating sympathetic mediation. Conclusions —These studies provide direct microneurographic evidence in humans that intranasal cocaine stimulates central sympathetic outflow. This central sympathetic activation appears to be targeted not only to the cutaneous circulation promoting peripheral vasoconstriction but also to the heart promoting tachycardia.
Aspirin-intolerance as a precipitating factor of life-threatening attacks of asthma requiring mechanical ventilation
Authors: C Picado, JA Castillo, JM Montserrat, A Agusti-Vidal
Journal: European Respiratory Journal (1989)

The records of 92 asthmatics who underwent mechanical ventilation were reviewed. In seven patients (8%) the severe attack was precipitated by a non-steroidal anti-inflammatory drug (NSAID); one of these patients died. Five of the cases had a history of asthmatic attacks provoked by NSAIDs; whilst in two the severe attack requiring mechanical ventilation was the first manifestation of NSAID-intolerance. In two patients the NSAID had been prescribed by their physicians. Another aspirin-intolerant patient, a general practitioner, self-administered a NSAID. The sudden attack in another patient was precipitated by a preparation which contains aspirin and is usually recommended for indigestion. In the fatal case the attack was provoked by a capsule containing aspirin, which had been given by a herbalist. Unlike other reports, we found that NSAID-intolerance is a frequent provoking factor in severe acute asthma requiring mechanical ventilation. Inadequate investigation of precipitating factors in asthmatics with severe sudden attacks is a possible reason why this phenomenon is underreported.
Mirroring cannot account for understanding action
Authors: Jeremy I. M. Carpendale, Charlie Lewis
Journal: Behavioral and Brain Sciences (2008)

Abstract Susan Hurley's shared circuits model (SCM) rightly begins in action and progresses through a series of layers; but it fails to reach action understanding because it relies on mirroring as a driving force, draws on heavily criticized theories, and neglects the need for shared experience in our grasp of social understanding.
The TGR5 receptor mediates bile acid–induced itch and analgesia
Authors: Farzad Alemi, Edwin Kwon, Daniel P. Poole, TinaMarie Lieu, Victoria Lyo, Fiore Cattaruzza, Ferda Cevikbas, Martin Steinhoff, Romina Nassini, Serena Materazzi, Raquel Guerrero-Alba, Eduardo Valdez-Morales, Graeme S. Cottrell, Kristina Schoonjans, Pierangelo Geppetti, Stephen J. Vanner, Nigel W. Bunnett, Carlos U. Corvera
Journal: Journal of Clinical Investigation (2013)

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucine-enkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide- and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.
Tackling Formalin-Fixed, Paraffin-Embedded Tumor Tissue with Next-Generation Sequencing
Authors: Christopher L. Corless, Paul T. Spellman
Journal: Cancer Discovery (2012)

Abstract Most tumor samples available for clinical genotyping are formalin-fixed and paraffin-embedded (FFPE), but there has been relatively little published on the suitability of such samples for next-generation sequencing approaches. A new study by Wagle and colleagues shows that a combination of hybridization-capture and deep sequencing yields high-quality data from FFPE specimens. Cancer Discovery; 2(1); 23–4. ©2012 AACR. Commentary on Wagle et al., p. 82.
38 TREATMENT OF SEVERE ACUTE ALCOHOLIC HEPATITIS (AAH) WITH CORTICOIDS PLUS N-ACETYL CYSTEINE (C-NAC) VERSUS CORTICOIDS (C): PLANED INTERIM ANALYSIS OF A MULTICENTRE, CONTROLLED, RANDOMIZED TRIAL
Authors: E. Nguyen-Khac, T. Thevenot, M.A. Piquet, D. Chatelain, B. Tramier, F. Dewael, S. Benferhat, A. Hezam, O. Goria, B. Bernard-Chabert, T. Yzet, J.L. Dupas
Journal: Journal of Hepatology (2008)