tbuckley/cabot-search huggingface dataset:
Randomized Multicenter Comparison of Conventional Anticoagulation Versus Antiplatelet Therapy in Unplanned and Elective Coronary Stenting
Authors: Michel E. Bertrand, Victor Legrand, Jean Boland, Eckart Fleck, Johannes Bonnier, Hakan Emmanuelson, Matty Vrolix, Luc Missault, Sergio Chierchia, Michele Casaccia, Luigi Niccoli, Ali Oto, Christopher White, Michael Webb-Peploe, Eric Van Belle, Eugène P. McFadden
Journal: Circulation (1998)

Background —Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. Methods —Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. Results —In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P =0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P =0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3±3.6 versus 6.4±3.7 days, P =0.0001). Conclusions —Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.
Impaired Conduction of Vasodilation Along Arterioles in Connexin40-Deficient Mice
Authors: Cor de Wit, Frederik Roos, Steffen-Sebastian Bolz, Susanne Kirchhoff, Olaf Krüger, Klaus Willecke, Ulrich Pohl
Journal: Circulation Research (2000)

Connexins have been hypothesized to play an important role in intercellular communication within the vascular wall and may provide a mechanistic explanation for conduction of vasomotor responses. To test this hypothesis, we studied the transmission of vasomotor responses in the intact skeletal muscle microcirculation of connexin40-deficient mice (Cx40(-/-)). Arterioles were locally stimulated with hyperpolarizing dilators (acetylcholine [ACh] as well as bradykinin [Bk]) or depolarizing K(+) solution, and the resulting changes in diameter were measured using a videomicroscopy technique at the site of application and up to 1.32 mm upstream. Arterial pressure was elevated 25% in Cx40(-/-) mice (94+/-5 versus 75+/-4 mm Hg). Vessels selected for study had equivalent basal diameter and vasomotor tone in both genotypes of mice. Vasomotion was present in small arterioles of both genotypes, but its intensity was exaggerated in Cx40(-/-) mice. ACh and Bk induced dilation (33% and 53%, respectively, of maximal response) at the site of application that was of similar magnitude in both genotypes. These dilations were observed to spread upstream within <1 second without significant attenuation in Cx40(+/+) mice. However, spreading was severely attenuated in Cx40(-/-) animals (11+/-4% versus 35+/-7% with ACh and 38+/-5% versus 60+/-7% with Bk in Cx40(-/-) and Cx40(+/+), respectively; P<0.05). In contrast, conducted vasoconstrictions, induced by K(+) solution decreased equally with distance in both genotypes. These results support a significant role for Cx40 in vascular intercellular communication. Our observations indicate that Cx40 is required for normal transmission of endothelium-dependent vasodilator responses and may underlie altered vasomotion patterns.
Dietary Polyunsaturated Fatty Acid Regulation of Gene Transcription
Authors: S D Clarke, D B Jump
Journal: Annual Review of Nutrition (1994)

We have known for nearly 30 years that dietary polyenoic (n-6) and (n-3) fatty acids potentially inhibit hepatic fatty acid biosynthesis. The teleological explanation for this unique action of PUFAs resides in their ability to suppress the synthesis of (n-9) fatty acids. By inhibiting fatty acid biosynthesis, dietary PUFAs reduce the availability of substrate for delta 9 desaturase (7, 22, 34, 36) and in turn reduce the availability of (n-9) fatty acids for incorporation into plasma membranes. In this way, essential biological processes dependent on essential fatty acids (e.g. reproduction and trans-dermal water loss) continue to operate normally. Therefore, if essential fatty acid intake did not regulate (n-9) fatty acid synthesis, the survival of the organism would be threatened. During the past 20 years, we have gradually elucidated the cellular and molecular mechanisms by which dietary PUFAs modulate fatty acid biosynthesis and (n-9) fatty acid availability. Central to this mechanism has been our ability to determine that dietary PUFAs regulate the transcription of genes coding for lipogenic enzymes (12, 40). The potential mechanisms by which PUFAs govern gene transcription are numerous, and it is unlikely that any one mechanism can fully elucidate the nuclear actions of PUFA. The difficulty in providing a unifying hypothesis at this time stems from: (a) the many metabolic routes taken by PUFAs upon entering the hepatocyte (Figure 1); and (b) the lack of identity of a specific PUFA-regulated trans-acting factor. However, the studies described above indicate that macronutrients, like PUFA, are not only utilized as fuel and structural components of cells, but also serve as important mediators of gene expression (12, 14, 40). As regulators of gene expression, PUFAs (or metabolites) are thought to affect the activity of transcription factors, which in turn target key cis-linked elements associated with specific genes. Whether this targeting involves DNA-protein interaction or the interaction of PUFA-regulated factors is unclear. A better understanding of the nuclear actions of PUFA will clarify the role of these compounds in lipid metabolism and lead to a better understanding of the role of PUFAs in disease processes such as insulin-resistant diabetes and certain forms of cancer.
Comparison of the Berlin Definition for Acute Respiratory Distress Syndrome with Autopsy
Authors: Arnaud W. Thille, Andrés Esteban, Pilar Fernández-Segoviano, José-Maria Rodriguez, José-Antonio Aramburu, Oscar Peñuelas, Irene Cortés-Puch, Pablo Cardinal-Fernández, José A. Lorente, Fernando Frutos-Vivar
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

A revised definition of clinical criteria for acute respiratory distress syndrome (ARDS), the Berlin definition, was recently established to classify patients according to their severity.To evaluate the accuracy of these clinical criteria using diffuse alveolar damage (DAD) at autopsy as the reference standard.All patients who died and had a clinical autopsy in our intensive care unit over a 20-year period (1991-2010) were included. Patients with clinical criteria for ARDS were identified from the medical charts and were classified as mild, moderate, or severe according to the Berlin definition using PaO2/FiO2 oxygenation criteria. Microscopic analysis from each pulmonary lobe was performed by two pathologists.Among 712 autopsies analyzed, 356 patients had clinical criteria for ARDS at time of death, classified as mild (n = 49, 14%), moderate (n = 141, 40%), and severe (n = 166, 46%). Sensitivity was 89% and specificity 63% to identify ARDS using the Berlin definition. DAD was found in 159 of 356 (45%) patients with clinical criteria for ARDS (in 12, 40, and 58% of patients with mild, moderate, and severe ARDS, respectively). DAD was more frequent in patients who met clinical criteria for ARDS during more than 72 hours and was found in 69% of those with severe ARDS for 72 hours or longer.Histopathological findings were correlated to severity and duration of ARDS. Using clinical criteria the revised Berlin definition for ARDS allowed the identification of severe ARDS of more than 72 hours as a homogeneous group of patients characterized by a high proportion of DAD.
Hormone Receptor, Grade, Human Epidermal Growth Factor Receptor 2, and Topoisomerase II As Predictors of Response to Chemotherapy
Authors: Rita S. Mehta
Journal: Journal of Clinical Oncology (2008)

TO THE EDITOR: Pritchard et al report an interaction among human epidermal growth factor receptor 2 (HER-2) status and anthracycline and taxane chemosensitivity in their review, but they do not mention tumor grade. Multivariate analysis has revealed that Scarff-Bloom-Richardson grade 3 tumors respond better to neoadjuvant treatment than Scarff-Bloom-Richardson grade 1 tumors (P .0001). A recent study suggests that an interaction between HER-2 and estrogen-receptor pathways may lead to a higher proliferation rate and thus a higher tumor grade. Therefore, inclusion of tumor grade in all the reviewed trials would have provided the relative predictive value of HER-2 status and grade in predicting anthracycline and taxane chemosensitivity. Moreover, among patients who have HER2–negative, estrogen receptor–positive and or progesterone receptor– positive breast cancer, those with higher tumor grades may benefit from anthracycline and taxanes. Furthermore, patients who have HER-2–negative, estrogen receptor–negative, and progesterone receptor–negative breast cancer, there is a high rate of pathologic complete response, specifically with anthracyclines administered biweekly compared with every 3 weeks, and paclitaxel administered weekly compared with every 3 weeks, and thus improved survival. Of the prospectively maintained database of 14 patients with stage II-III or local relapse HER-2–negative, estrogen receptor–negative, and progesterone receptor–negative infiltrating ductal carcinoma of breast who received dose-dense doxorubicin and cyclophosphamide followed by either dose-dense paclitaxel (n 2) or once-a-week paclitaxel (cremophoror albumin-bound) with carboplatin (both 3 weeks on, 1 week off; n 12) plus or minus six doses of bevacizumab every 2 weeks (n 4), 10 (71%; 95% CI, 42% to 92%) of 14 patients achieved pathologic complete response. The progression-free survival of 86% of 14 patients at a median follow-up of 33 months is promising. Therefore, the high pathologic complete response reported by us parallels the benefit of biweekly anthracyclines, and biweekly or weekly paclitaxel scheduling in phase III trials. In an otherwise comprehensive review by Pritchard et al, it needs to be emphasized that within patients with HER-2–negative tumors, patients with estrogen receptor–negative and progesterone receptor–negative subtype (triple-negative), or patients with higher tumor grade, optimally scheduled doxorubicin and cyclophosphamide and paclitaxel should be standard. The potential additional benefit of carboplatin and bevacizumab over optimum scheduling of standard chemotherapy needs to be tested in randomized trials.
The Attention System of the Human Brain: 20 Years After
Authors: Steven E. Petersen, Michael I. Posner
Journal: Annual Review of Neuroscience (2012)

Here, we update our 1990 Annual Review of Neuroscience article, “The Attention System of the Human Brain.” The framework presented in the original article has helped to integrate behavioral, systems, cellular, and molecular approaches to common problems in attention research. Our framework has been both elaborated and expanded in subsequent years. Research on orienting and executive functions has supported the addition of new networks of brain regions. Developmental studies have shown important changes in control systems between infancy and childhood. In some cases, evidence has supported the role of specific genetic variations, often in conjunction with experience, that account for some of the individual differences in the efficiency of attentional networks. The findings have led to increased understanding of aspects of pathology and to some new interventions.
Prognostic Stratification of Stage IIIA-N2 Non–Small-Cell Lung Cancer After Induction Chemotherapy: A Model Based on the Combination of Morphometric-Pathologic Response in Mediastinal Nodes and Primary Tumor Response on Serial 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography
Authors: Christophe Dooms, Eric Verbeken, Sigrid Stroobants, Kris Nackaerts, Paul De Leyn, Johan Vansteenkiste
Journal: Journal of Clinical Oncology (2008)

Surgical resection in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) is usually reserved for patients with mediastinal downstaging after induction chemotherapy (IC). However, clinical restaging is often inaccurate, and there are insufficient data to conclude that all patients with persistent mediastinal disease will not benefit from surgery, or that all patients with mediastinal clearance benefit from surgery. We created a data-based restaging strategy combining morphometric tissue analysis of mediastinal lymph nodes (LNs) and 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) response monitoring in the primary tumor.Baseline and repeat FDG-PET after IC, as well as complete resection specimens of both mediastinal LNs and primary tumor, were available in 30 patients. Histologic response grading was performed by means of conventional morphometric procedures. Mediastinal response grading combined with the percentage decrease of maximum standardized uptake value (SUV(max)) on the primary tumor was correlated with survival.Patients with persistent major mediastinal LN involvement have a 5-year overall survival rate of 0%. The 5-year overall survival rate for patients with cleared or persistent minor mediastinal LN involvement was significantly higher in patients with a more than 60% decrease in SUV(max) on the primary tumor as compared with patients with a less than 60% decrease in SUV(max) (62% v 13%; log-rank P = .002).These data may suggest that (1) persistent mediastinal disease after IC does not always exclude favorable outcome after surgery; (2) serial FDG-PET may select surgical candidates among patients with mediastinal downstaging or persistent minor disease; (3) persistent major mediastinal disease has a poor prognosis and such patients should not be considered for surgery.
1015 TUMOR NECROSIS FACTOR-ALPHA PROMOTER GENE POLYMORPHISM IN RELATION TO RECURRENCE OF HEPATOCELLULAR CARCINOMA FOLLOWING COMPLETE REMISSION BY LOCOREGIONAL THERAPY
Authors: S.E. Kim, D. Lee, Y.-H. Chung, J.A. Kim, E.-S. Shin, W.H. Park, J.H. Shim, H.K. Yoon, P.N. Kim, K.B. Sung, J.-E. Lee
Journal: Journal of Hepatology (2012)
A rigorous approach for testing the constructionist hypotheses of brain function
Authors: Gopikrishna Deshpande, K. Sathian, Xiaoping Hu, Joseph A. Buckhalt
Journal: Behavioral and Brain Sciences (2012)

Abstract Although the target article provides strong evidence against the locationist view, evidence for the constructionist view is inconclusive, because co-activation of brain regions does not necessarily imply connectivity between them. We propose a rigorous approach wherein connectivity between co-activated regions is first modeled using exploratory Granger causality, and then confirmed using dynamic causal modeling or Bayesian modeling.
A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study
Authors: Dae Hyun Yoo, Pawel Hrycaj, Pedro Miranda, Edgar Ramiterre, Mariusz Piotrowski, Sergii Shevchuk, Volodymyr Kovalenko, Nenad Prodanovic, Mauricio Abello-Banfi, Sergio Gutierrez-Ureña, Luis Morales-Olazabal, Michael Tee, Renato Jimenez, Omid Zamani, Sang Joon Lee, HoUng Kim, Won Park, Ulf Müller-Ladner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. <h3>Methods</h3> Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. <h3>Results</h3> At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. <h3>Conclusions</h3> CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. <h3>ClinicalTrials.gov Identifier</h3> NCT01217086
Treatment strategies and outcome of induction-refractory Wegener's granulomatosis or microscopic polyangiitis: analysis of 32 patients with first-line induction-refractory disease in the WEGENT trial
Authors: Raphaèle Seror, Christian Pagnoux, Marc Ruivard, Isabelle Landru, Denis Wahl, Sophie Rivière, Solveig Aussant, Alfred Mahr, Pascal Cohen, Luc Mouthon, Loïc Guillevin
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To study the efficacy of rescue treatment strategies and outcomes in patients with Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) not achieving remission with first-line induction with corticosteroids (CS) and intravenous cyclophosphamide (CYC). Methods 159 eligible patients in the Wegener's Granulomatosis-Entretien (WEGENT) trial newly diagnosed with systemic or renal WG or MPA with ≥1 poor prognosis factors were included in this prospective study. Rescue treatment strategies and outcomes in patients with induction-refractory disease were analysed and patient characteristics at diagnosis were compared with those of induction-responders. Results Most patients (n=126, 79.2%) achieved remission; 1 stopped induction because of allergy and 32 were induction-refractory (24 WG and 8 MPA); 11 died rapidly within a median of 2.5 months, 6 of uncontrolled disease, 1 of an infectious complication and 4 of both. Treatment was discontinued in 1 patient with MPA with end-stage renal disease. Induction was switched to oral CYC in 20 patients, combined with infliximab in 1; 15 (75%) achieved remission or low disease activity state, 3 subsequently died of uncontrolled disease and 2 entered remission using several other agents including biological agents. Alveolar haemorrhage and a creatinine level &gt;200 μmol/l were independently associated with induction-refractory disease. Among patients with induction-refractory disease, massive alveolar haemorrhage was associated with higher mortality. Conclusion Switching to oral CYC can be an effective rescue treatment for patients with systemic forms of WG or MPA who fail to achieve remission with first-line CS and intravenous CYC. However, a more rapidly effective regimen remains to be identified for most severely affected patients whose outcomes can be rapidly fatal.
Effect of a community-led sanitation intervention on child diarrhoea and child growth in rural Mali: a cluster-randomised controlled trial
Authors: Amy J Pickering, Habiba Djebbari, Carolina Lopez, Massa Coulibaly, Maria Laura Alzua
Journal: The Lancet Global Health (2015)

BackgroundCommunity-led total sanitation (CLTS) uses participatory approaches to mobilise communities to build their own toilets and stop open defecation. Our aim was to undertake the first randomised trial of CLTS to assess its effect on child health in Koulikoro, Mali.MethodsWe did a cluster-randomised trial to assess a CLTS programme implemented by the Government of Mali. The study population included households in rural villages (clusters) from the Koulikoro district of Mali; every household had to have at least one child aged younger than 10 years. Villages were randomly assigned (1:1) with a computer-generated sequence by a study investigator to receive CLTS or no programme. Health outcomes included diarrhoea (primary outcome), height for age, weight for age, stunting, and underweight. Outcomes were measured 1·5 years after intervention delivery (2 years after enrolment) among children younger than 5 years. Participants were not masked to intervention assignment. The trial is registered with ClinicalTrials.gov, number NCT01900912.FindingsWe recruited participants between April 12, and June 23, 2011. We assigned 60 villages (2365 households) to receive the CLTS intervention and 61 villages (2167 households) to the control group. No differences were observed in terms of diarrhoeal prevalence among children in CLTS and control villages (706 [22%] of 3140 CLTS children vs 693 [24%] of 2872 control children; prevalence ratio [PR] 0·93, 95% CI 0·76–1·14). Access to private latrines was almost twice as high in intervention villages (1373 [65%] of 2120 vs 661 [35%] of 1911 households) and reported open defecation was reduced in female (198 [9%] of 2086 vs 608 [33%] of 1869 households) and in male (195 [10%] of 2004 vs 602 [33%] of 1813 households) adults. Children in CLTS villages were taller (0·18 increase in height-for-age Z score, 95% CI 0·03–0·32; 2415 children) and less likely to be stunted (35% vs 41%, PR 0·86, 95% CI 0·74–1·0) than children in control villages. 22% of children were underweight in CLTS compared with 26% in control villages (PR 0·88, 95% CI 0·71–1·08), and the difference in mean weight-for-age Z score was 0·09 (95% CI –0·04 to 0·22) between groups. In CLTS villages, younger children at enrolment (<2 years) showed greater improvements in height and weight than older children.InterpretationIn villages that received a behavioural sanitation intervention with no monetary subsidies, diarrhoeal prevalence remained similar to control villages. However, access to toilets substantially increased and child growth improved, particularly in children <2 years. CLTS might have prevented growth faltering through pathways other than reducing diarrhoea.FundingBill & Melinda Gates Foundation.