tbuckley/cabot-search huggingface dataset:
Effectiveness of strategies incorporating training and support of traditional birth attendants on perinatal and maternal mortality: meta-analysis
Authors: A. Wilson, I. D. Gallos, N. Plana, D. Lissauer, K. S. Khan, J. Zamora, C. MacArthur, A. Coomarasamy
Journal: BMJ (2011)

<b>Objective</b> To assess the effectiveness of strategies incorporating training and support of traditional birth attendants on the outcomes of perinatal, neonatal, and maternal death in developing countries. <b>Design</b> Systematic review with meta-analysis. <b>Data sources</b> Medline, Embase, the Allied and Complementary Medicine database, British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, BioMed Central, PsycINFO, Latin American and Caribbean Health Sciences Literature database, African Index Medicus, Web of Science, Reproductive Health Library, and Science Citation Index (from inception to April 2011), without language restrictions. Search terms were "birth attend*", "traditional midwife", "lay birth attendant", "dais", and "comadronas". <b>Review methods</b> We selected randomised and non-randomised controlled studies with outcomes of perinatal, neonatal, and maternal mortality. Two independent reviewers undertook data extraction. We pooled relative risks separately for the randomised and non-randomised controlled studies, using a random effects model. <b>Results</b> We identified six cluster randomised controlled trials (n=138 549) and seven non-randomised controlled studies (n=72 225) that investigated strategies incorporating training and support of traditional birth attendants. All six randomised controlled trials found a reduction in adverse perinatal outcomes; our meta-analysis showed significant reductions in perinatal death (relative risk 0.76, 95% confidence interval 0.64 to 0.88, P&lt;0.001; number needed to treat 35, 24 to 70) and neonatal death (0.79, 0.69 to 0.88, P&lt;0.001; 98, 66 to 170). Meta-analysis of the non-randomised studies also showed a significant reduction in perinatal mortality (0.70, 0.57 to 0.84, p&lt;0.001; 48, 32 to 96) and neonatal mortality (0.61, 0.48 to 0.75, P&lt;0.001; 96, 65 to 168). Six studies reported on maternal mortality and our meta-analysis showed a non-significant reduction (three randomised trials, relative risk 0.79, 0.53 to 1.05, P=0.12; three non-randomised studies, 0.80, 0.44 to 1.15, P=0.26). <b>Conclusion</b> Perinatal and neonatal deaths are significantly reduced with strategies incorporating training and support of traditional birth attendants.
Functional Neuroimaging of Avoidance Habits in Obsessive-Compulsive Disorder
Authors: Claire M. Gillan, Annemieke M. Apergis-Schoute, Sharon Morein-Zamir, Gonzalo P. Urcelay, Akeem Sule, Naomi A. Fineberg, Barbara J. Sahakian, Trevor W. Robbins
Journal: American Journal of Psychiatry (2014)

Objective: The purpose of this study was to determine the neural correlates of excessive habit formation in obsessive-compulsive disorder (OCD). The authors aimed to test for neurobiological convergence with the known pathophysiology of OCD and to infer, based on abnormalities in brain activation, whether these habits arise from dysfunction in the goal-directed or habit system. Method: Thirty-seven OCD patients and 33 healthy comparison subjects learned to avoid shocks while undergoing a functional MRI scan. Following four blocks of training, the authors tested whether the avoidance response had become a habit by removing the threat of shock and measuring continued avoidance. Task-related differences in brain activity in three regions of interest (the caudate, the putamen, and the medial orbitofrontal cortex) were tested at a statistical threshold set at <0.05 (family-wise-error corrected). Results: Excessive habit formation in OCD patients, which was associated with hyperactivation in the caudate, was observed. Activation in this region was also associated with subjective ratings of increased urge to perform habits. The OCD group, as a whole, showed hyperactivation in the medial orbitofrontal cortex during the acquisition of avoidance; however, this did not relate directly to habit formation. Conclusions: OCD patients exhibited excessive habits that were associated with hyperactivation in a key region implicated in the pathophysiology of OCD, the caudate nucleus. Previous studies indicate that this region is important for goal-directed behavior, suggesting that habit-forming biases in OCD may be a result of impairments in this system, rather than differences in the buildup of stimulus-response habits themselves.
Prediction of Survival in Follicular Lymphoma Based on Molecular Features of Tumor-Infiltrating Immune Cells
Authors: Sandeep S. Dave, George Wright, Bruce Tan, Andreas Rosenwald, Randy D. Gascoyne, Wing C. Chan, Richard I. Fisher, Rita M. Braziel, Lisa M. Rimsza, Thomas M. Grogan, Thomas P. Miller, Michael LeBlanc, Timothy C. Greiner, Dennis D. Weisenburger, James C. Lynch, Julie Vose, James O. Armitage, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Jan Delabie, Joseph M. Connors, Peter M. Lansdorp, Qin Ouyang, T. Andrew Lister, Andrew J. Davies, Andrew J. Norton, H. Konrad Muller-Hermelink, German Ott, Elias Campo, Emilio Montserrat, Wyndham H. Wilson, Elaine S. Jaffe, Richard Simon, Liming Yang, John Powell, Hong Zhao, Neta Goldschmidt, Michael Chiorazzi, Louis M. Staudt
Journal: New England Journal of Medicine (2004)

Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival.Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens.Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells.The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Imbalance of power between patients and doctors
Authors: Christian Koeck
Journal: BMJ (2014)

The price of ignoring the shadow 

The human capacity to understand the world is truly astonishing. What began with a taste of the fruit from the “tree of good and evil,” has developed into our unlimited capacity to separate, differentiate, define, and analyse. Consequently, the natural sciences have handed humanity previously unimaginable powers to control and shape the world. In the words of Susan Sontag, we have expanded the boundaries of the kingdom of the well and gained control of significant parts of the kingdom of the sick.1

To make this possible, society has provided vast resources to the medical sector and given physicians powers no other profession has: to open the human body, to prescribe potentially lethal substances, and to cut, pierce, and replace organs and body parts. With great powers come great responsibilities and fears. In the “Role of fear in overdiagnosis and overtreatment,” Iona Heath eloquently described the everyday inner conflicts of patients and doctors. …
A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB.
Authors: J Zhao, G J Freeman, G S Gray, L M Nadler, L H Glimcher
Journal: The Journal of Experimental Medicine (1996)

The costimulatory molecule B7.1 provides a second signal critical for T cell activation. The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli. To identify the molecular basis for specificity and inducibility, the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types. The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region. This 183-bp region was both cell type specific and responsive to two distinct stimuli, lipopolysaccharide and dibutyryl cAMP, known to regulate B7.1 expression. Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region, one of which was a nuclear factor (NF)-kappaB consensus sequence. In B7.1-positive B cells, this element bound several members of the NF-kappaB family, transcription factors already implicated in signal transduction pathways relevant to B7.1 expression. This is the first description, to our knowledge, of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule.
Human T-Cell Lymphotropic Virus Type I-Infected Cells Extravasate through the Endothelial Barrier by a Local Angiogenesis-Like Mechanism
Authors: Ali Bazarbachi, Raghida Abou Merhi, Antoine Gessain, Rabih Talhouk, Hilda El-Khoury, Rihab Nasr, Olivier Gout, Rita Sulahian, Fadia Homaidan, Hugues de Thé, Olivier Hermine, Marwan E. El-Sabban
Journal: Cancer Research (2004)

Abstract Extravasation of tumor cells through the endothelial barrier is a critical step in cancer metastasis. Human T-cell lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive disease characterized by visceral invasion. We show that ATL and HTLV-I-associated myelopathy patients exhibit high plasma levels of functional vascular endothelial growth factor and basic fibroblast growth factor. The viral oncoprotein Tax transactivates the promoter of the gap-junction protein connexin-43 and enhances gap-junction-mediated heterocellular communication with endothelial cells. The interaction of HTLV-I-transformed cells with endothelial cells induces the gelatinase activity of matrix metalloproteinase (MMP)-2 and MMP-9 in endothelial cells and down-regulates the tissue inhibitor of MMP. This leads to subendothelial basement membrane degradation followed by endothelial cell retraction, allowing neoplastic lymphocyte extravasation. We propose a model that offers a mechanistic explanation for extravasation of HTLV-I-infected cells: after specific adhesion to endothelia of target organs, tumor cells induce a local and transient angiogenesis-like mechanism through paracrine stimulation and direct cell-cell communication with endothelial cells. This culminates in a breach of the endothelial barrier function, allowing cancer cell invasion. This local and transient angiogenesis-like sequence that may facilitate visceral invasion in ATL represents a potential target for ATL therapy.
Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study.
Authors: David M Kendall, Cindy J Rubin, Pharis Mohideen, Jean-Marie Ledeine, Rene Belder, Jorge Gross, Paul Norwood, Michael O'Mahony, Kenneth Sall, Greg Sloan, Anthony Roberts, Fred T Fiedorek, Ralph A DeFronzo
Journal: Diabetes Care (2006)

We sought to evaluate the effects of muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor (PPAR) activator within the new glitazar class, on hyperglycemia and lipid abnormalities.A double-blind, randomized, controlled trial was performed in 1,159 patients with type 2 diabetes inadequately controlled with metformin. Patients received once-daily doses of either 5 mg muraglitazar or 30 mg pioglitazone for a total of 24 weeks in addition to open-label metformin. Patients were continued in a double-blind fashion for an additional 26 weeks.Analyses were conducted at week 24 for HbA1c (A1C) and at week 12 for lipid parameters. Mean A1C at baseline was 8.12 and 8.13% in muraglitazar and pioglitazone groups, respectively. At week 24, muraglitazar reduced mean A1C to 6.98% (-1.14% from baseline), and pioglitazone reduced mean A1C to 7.28% (-0.85% from baseline; P < 0.0001, muraglitazar vs. pioglitazone). At week 12, muraglitazar and pioglitazone reduced mean plasma triglyceride (-28 vs. -14%), apolipoprotein B (-12 vs. -6%), and non-HDL cholesterol (-6 vs. -1%) and increased HDL cholesterol (19 vs. 14%), respectively (P < 0.0001 vs. pioglitazone for all comparisons). At week 24, weight gain (1.4 and 0.6 kg, respectively) and edema (9.2 and 7.2%, respectively) were observed in the muraglitazar and pioglitazone groups; at week 50, weight gain and edema were 2.5 and 1.5 kg, respectively, and 11.8 and 8.9%, respectively. At week 50, heart failure was reported in seven patients (five with muraglitazar and two with pioglitazone), and seven deaths occurred: three from sudden death, two from cerebrovascular accident, and one from pancreatic cancer in the muraglitazar group and one from perforated duodenal ulcer in the pioglitazone group.We found that 5 mg muraglitazar resulted in greater improvements in A1C and lipid parameters than a submaximal dose of 30 mg pioglitazone when added to metformin. Weight gain and edema were more common when muraglitazar was compared with a submaximal dose of pioglitazone.
MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies
Authors: K Tsuboi, S Iida, H Inagaki, M Kato, Y Hayami, I Hanamura, K Miura, S Harada, M Kikuchi, H Komatsu, S Banno, A Wakita, S Nakamura, T Eimoto, R Ueda
Journal: Leukemia (2000)
Respiratory and upper airways impedance responses to methacholine inhalation in spontaneously breathing cats
Authors: N. Loos, R. Peslin, F Marchal
Journal: European Respiratory Journal (2000)

The upper airways may contribute to the increase in respiratory resistance induced by methacholine (Mch). The aim of this study was to simultaneously assess the Mch response of upper airways and lower respiratory resistances (Rua, Rrs,lo) and reactances (Xua, Xrs,lo), and to test whether the change of total respiratory resistance and reactance after Mch were affected by upper airways mechanisms. Seven cats breathing spontaneously were studied under chloralose, urethane anaesthesia. Forced oscillations were generated at 20 Hz by a loud-speaker connected to the pharyngeal cavity. A pneumotachograph was placed between rostral and caudal extremities of the severed cervical trachea. Pressure drops were measured across the upper airways and across the lower respiratory system. Rua, Xua, Rrs,lo and Xrs,lo were obtained after nebulized normal saline and Mch administered directly through the tracheostomy. The analysis focused on Mch tests showing clear positive upper airways response. Volume and flow dependence of Rrs,lo and Rua were assessed during tidal inspiration using multiple linear regression analysis. After Mch, Rrs,lo increased and became negatively volume dependent, while the increase in Rua was associated with no significant change in volume dependence; Xrs,lo became negative while Xua did not change. The upper airways response to methacholine may thus contribute to the increase in total respiratory resistance but may not account for either its negative volume dependence or the decrease in total resistance. It is surmised that these features more specifically reflect alterations in respiratory mechanics occurring at the level of the intrathoracic airways.
Gender differences in formation of endothelial dysfunction (ED) extension in COPD patients
Authors: Lyudmyla Konopkina, Tetyana Pertseva
Journal: European Respiratory Journal (2011)

ED is one of the most important branches in pathogenesis of cardio-vascular events (CVE). It is established that soluble intercellular adhesion molecule-1 (sICAM-1) is one of the markers of ED. But it is known little about ED in COPD patients (pts) particularly in accordance with gender features.   Aim:  To study the ability in prognosis of ED extension in COPD pts due to gender.  We studied 93 pts in stable phase of COPD, divided into 2 groups: 1st – 61 (65.6%) male (age – 63.0±1.1 yrs, 56 (91,8%) smokers with index “pack/year” – 38.7±2.7), 2nd – 32 (34.4%) female (age – 57.5±1.9 yrs, 8 (25%) smokers with “pack/year” – 16.5±3.9). Measurements included clinical status, spirometry, serum level of sICAM-1 (ng/ml) by ELISA.   Results:  The level of sICAM-1 was significantly higher in male with COPD than in health male, but there were no differences between levels of sICAM-1 in female with COPD and in health female (table). Due to stages of COPD there was no correlation between sICAM-1 and FEV 1  in the 1st group (r=0.175 (p>0.05)), but there was negative correlation in the 2nd group (r= -0.373 (p=0.046)).   Conclusion:  Male sex is a risk-factor of ED extension and CVE in COPD pts in the whole, but female sex is a risk-factor of ED extension and CVE only during progression of COPD.
Validation of Patient's Self-Reported Social Functioning As an Independent Prognostic Factor for Survival in Metastatic Colorectal Cancer Patients: Results of an International Study by the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer
Authors: Fabio Efficace, Pasquale F. Innominato, Georg Bjarnason, Corneel Coens, Yves Humblet, Salvatore Tumolo, Dominique Genet, Marco Tampellini, Andrew Bottomley, Carlo Garufi, Christian Focan, Sylvie Giacchetti, Francis Lévi
Journal: Journal of Clinical Oncology (2008)

A recent study identified a prognostic model for survival in metastatic colorectal cancer patients which included WBC count, alkaline phosphatase (AP), number of metastatic sites, and patients' self-reported social functioning. The aim of this research is to validate this model on data from an independent sample.This validation study is based on a prospective randomized controlled trial in patients with metastatic colorectal cancer conducted by the European Organisation for Research and Treatment of Cancer (EORTC) Chronotherapy Group. Overall, 564 patients in 10 countries were enrolled. For the purpose of this independent validation, patients with health-related quality of life (HRQOL) baseline data were analyzed. HRQOL was assessed using the EORTC Quality of Life Questionnaire C30 (QLQ-C30). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival.The previous model with an additional adjustment, by stratification for sex, was replicated and its parameters were confirmed to independently predict survival: WBC count with an hazard ratio (HR) of 1.31 (95% CI, 1.021 to 1.698; P = .034); AP with an HR of 1.53 (95% CI, 1.188 to 1.979; P = .001); number of sites involved with an HR of 1.90 (95% CI, 1.531 to 2.364; P < .0001); and patients' self-reported social functioning with an HR of 0.94 (95% CI, 0.905 to 0.976; P = .001). The latter translates into a 6% increase in the likelihood of an earlier death for every 10-point decrease in the social functioning scale of the EORTC QLQ-C30.This study provides confirmatory evidence of the independent prognostic value of patients' self-reported social functioning in patients with advanced colorectal cancer.
1404 DIAGNOSIS, PREVALENCE, AND PROGNOSIS OF ACUTE-ON- CHRONIC LIVER FAILURE (ACLF): RESULTS OF THE EASL-CHRONIC LIVER FAILURE (CLIF) CONSORTIUM CANONIC STUDY
Authors: R. Moreau, P. Gines, R. Jalan, M. Pavesi, F. Durand, P. Angeli, P. Caraceni, G. Pereira, C. Hopf, C. Alessandria, P. Solis, W. Laleman, J. Trebicka, F. Saliba, S. Zeuzem, A. Albillos, T. Gustot, M. Yago, L. Elkrief, D. Benten, J.-L. Montero, T. Chiva, M. Concepción, J. Cordoba, A. McCormick, R.-E. Stauber, W. Vogel, A. De Gottardi, F. Morando, M. Domenicali, A.-L. Gerbes, A. Risso, E. García, C. Deulofeu, M. Bernardi, V. Arroyo
Journal: Journal of Hepatology (2012)
Genome-Wide Analysis of Promoter Methylation Associated with Gene Expression Profile in Pancreatic Adenocarcinoma
Authors: Audrey Vincent, Noriyuki Omura, Seung-Mo Hong, Andrew Jaffe, James Eshleman, Michael Goggins
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations. Experimental Design: We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27,800 CpG islands covering 21 MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues and in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual. Results: This analysis identified 1,658 known loci that were commonly differentially methylated in pancreatic cancer compared with normal pancreas. By integrating the pancreatic DNA methylation status with the gene expression profiles of the same samples before and after treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine, and the histone deacetylase inhibitor, trichostatin A, we identified dozens of aberrantly methylated and differentially expressed genes in pancreatic cancers including a more comprehensive list of hypermethylated and silenced genes that have not been previously described as targets for aberrant methylation in cancer. Conclusion: We expected that the identification of aberrantly hypermethylated and silenced genes will have diagnostic, prognostic, and therapeutic applications. Clin Cancer Res; 17(13); 4341–54. ©2011 AACR.