tbuckley/cabot-search huggingface dataset:
Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction in Patients With Preserved Ejection Fraction
Authors: Mads J. Andersen, Mads Ersbøll, Anna Axelsson, Finn Gustafsson, Christian Hassager, Lars Køber, Barry A. Borlaug, Søren Boesgaard, Lene T. Skovgaard, Jacob E. Møller
Journal: Circulation (2013)

Background— Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction. Methods and Results— Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P =0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P =0.07). However, with treatment cardiac index increased at rest ( P =0.006) and peak exercise ( P =0.02) in the sildenafil group, and systemic vascular resistance index (resting, P =0.0002; peak exercise, P =0.007) and diastolic blood pressure (resting, P =0.005; peak exercise, P =0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased ( P =0.001) within the sildenafil group but was unchanged in the placebo group. Conclusions— Sildenafil did not decrease filling pressure at rest or during exercise in post–myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov/ct2/show/NCT01046838 . Unique identifier: NCT01046838.
The mosaic structure of the symbiotic plasmid of Rhizobium etliCFN42 and its relation to other symbiotic genome compartments
Authors: Víctor González, Patricia Bustos, Miguel A Ramírez-Romero, Arturo Medrano-Soto, Heladia Salgado, Ismael Hernández-González, Juan Carlos Hernández-Celis, Verónica Quintero, Gabriel Moreno-Hagelsieb, Lourdes Girard, Oscar Rodríguez, Margarita Flores, Miguel A Cevallos, Julio Collado-Vides, David Romero, Guillermo Dávila
Journal: Genome biology (2003)
Association of Resident Fatigue and Distress With Perceived Medical Errors
Authors: Colin P. West, Angelina D. Tan, Thomas M. Habermann, Jeff A. Sloan, Tait D. Shanafelt
Journal: JAMA (2009)

<h3>Context</h3>Fatigue and distress have been separately shown to be associated with medical errors. The contribution of each factor when assessed simultaneously is unknown.<h3>Objective</h3>To determine the association of fatigue and distress with self-perceived major medical errors among resident physicians using validated metrics.<h3>Design, Setting, and Participants</h3>Prospective longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic, Rochester, Minnesota. Data were provided by 380 of 430 eligible residents (88.3%). Participants began training from 2003 to 2008 and completed surveys quarterly through February 2009. Surveys included self-assessment of medical errors, linear analog self-assessment of overall quality of life (QOL) and fatigue, the Maslach Burnout Inventory, the PRIME-MD depression screening instrument, and the Epworth Sleepiness Scale.<h3>Main Outcome Measures</h3>Frequency of self-perceived, self-defined major medical errors was recorded. Associations of fatigue, QOL, burnout, and symptoms of depression with a subsequently reported major medical error were determined using generalized estimating equations for repeated measures.<h3>Results</h3>The mean response rate to individual surveys was 67.5%. Of the 356 participants providing error data (93.7%), 139 (39%) reported making at least 1 major medical error during the study period. In univariate analyses, there was an association of subsequent self-reported error with the Epworth Sleepiness Scale score (odds ratio [OR], 1.10 per unit increase; 95% confidence interval [CI], 1.03-1.16; P = .002) and fatigue score (OR, 1.14 per unit increase; 95% CI, 1.08-1.21; P &lt; .001). Subsequent error was also associated with burnout (ORs per 1-unit change: depersonalization OR, 1.09; 95% CI, 1.05-1.12; P &lt; .001; emotional exhaustion OR, 1.06; 95% CI, 1.04-1.08; P &lt; .001; lower personal accomplishment OR, 0.94; 95% CI, 0.92-0.97; P &lt; .001), a positive depression screen (OR, 2.56; 95% CI, 1.76-3.72; P &lt; .001), and overall QOL (OR, 0.84 per unit increase; 95% CI, 0.79-0.91; P &lt; .001). Fatigue and distress variables remained statistically significant when modeled together with little change in the point estimates of effect. Sleepiness and distress, when modeled together, showed little change in point estimates of effect, but sleepiness no longer had a statistically significant association with errors when adjusted for burnout or depression.<h3>Conclusion</h3>Among internal medicine residents, higher levels of fatigue and distress are independently associated with self-perceived medical errors.
Airway responsiveness to hypertonic saline: dose-response slope or PD15?
Authors: G. de Meer
Journal: European Respiratory Journal (2005)

The result of airway challenge test with hypertonic saline (HS) is expressed as the dose causing a 15% fall in forced expiratory volume in one second (FEV1; PD15). A noncensored measure, such as the dose-response slope (DRS), allows the evaluation of the risk of asthma for subjects with a fall in FEV1 &lt;15%. The aim of this study was to assess the relationship between airway responsiveness to HS by PD15 or DRS, asthma symptoms and markers of eosinophilic inflammation. Data on current wheeze and airway responsiveness were obtained for 1,107 children (aged 8–13 yrs). Blood eosinophils and serum eosinophil cationic protein (ECP) were assessed in subsets (n = 683 and 485). PD15 was assessed if FEV1 fell ≥15%, and the DRS was calculated for all tests. Graphs were constructed to visualise relationships with current wheeze, blood eosinophils and serum ECP. Odds ratios and Spearman9s correlation coefficients were calculated to quantify these relationships. Children with features of asthma had lower PD15 and higher DRS, and separation was most pronounced for DRS. Prevalence of current wheeze increased continuously over the entire range of DRS values. Blood eosinophils were significantly higher only for the highest values of DRS. In conclusion, the continuous relationship between airway responsiveness and asthma symptoms is in favour of a noncensored measure of airway responsiveness, such as the dose-response slope.
Plasma Lipids, Genetic Variants Near<i>APOA1</i>, and the Risk of Infantile Hypertrophic Pyloric Stenosis
Authors: Bjarke Feenstra, Frank Geller, Lisbeth Carstensen, Paul A. Romitti, Izabella Baranowska Körberg, Bruce Bedell, Camilla Krogh, Ruzong Fan, Anna Svenningsson, Michele Caggana, Agneta Nordenskjöld, James L. Mills, Jeffrey C. Murray, Mads Melbye
Journal: JAMA (2013)

<h3>Importance</h3> Infantile hypertrophic pyloric stenosis (IHPS) is a serious condition in which hypertrophy of the pyloric sphincter muscle layer leads to gastric outlet obstruction. Infantile hypertrophic pyloric stenosis shows strong familial aggregation and heritability, but knowledge about specific genetic risk variants is limited. <h3>Objectives</h3> To search the genome comprehensively for genetic associations with IHPS and validate findings in 3 independent sample sets. <h3>Design, Setting, and Participants</h3> During stage 1, we used reference data from the 1000 Genomes Project for imputation into a genome-wide data set of 1001 Danish surgery-confirmed samples (cases diagnosed 1987-2008) and 2371 disease-free controls. In stage 2, the 5 most significantly associated loci were tested in independent case-control sample sets from Denmark (cases diagnosed 1983-2010), Sweden (cases diagnosed 1958-2011), and the United States (cases diagnosed 1998-2005), with a total of 1663 cases and 2315 controls. <h3>Main Outcomes and Measures</h3> Association of genetic variation with the presence of infantile hypertrophic pyloric stenosis. <h3>Results</h3> We found a new genome-wide significant locus for IHPS at chromosome 11q23.3. The single-nucleotide polymorphism (SNP) with the lowest<i>P</i>value at the locus, rs12721025 (odds ratio [OR], 1.59; 95% CI, 1.38-1.83;<i>P</i> = 1.9 × 10<sup>−10</sup>), is located 301 bases downstream of the apolipoprotein A-I (<i>APOA1</i>) gene and is correlated (<i>r2</i>between 0.46 and 0.80) with SNPs previously found to be associated with levels of circulating cholesterol. For these SNPs, the cholesterol-lowering allele consistently was associated with increased risk of IHPS. <h3>Conclusions and Relevance</h3> This study identified a new genome-wide significant locus for IHPS. Characteristics of this locus suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk, which warrants further investigation.
Embolization of uterine leiomyomata: current concepts in management
Authors: Peter Braude, John Reidy, Vicky Nott, Alison Taylor, Robert Forman
Journal: Human Reproduction Update (2000)

Transcatheter bilateral uterine artery embolization is a relatively new, but fast increasing modality being offered as an alternative to surgery for the treatment of symptomatic uterine fibroids (myomata). Since its introduction in 1995, it is estimated that over 5000 procedures have been performed, despite little objective evidence of its efficacy in comparison with more traditional surgical procedures, e.g. hysterectomy, abdominal or laparoscopic myomectomy or hysteroscopic procedures. The enthusiastic uptake of uterine artery embolization is partly due to the fact that it can be performed as a day case, and is a means of avoiding surgery especially hysterectomy. However, the procedure is not without significant risks, and these are becoming clearer as more procedures are being reported. This review examines the procedure, its use and purported efficacy and discusses its complications and potential hazards.
A conservative approach for subsolid lung nodules: is it safe enough?
Authors: Maurizio Infante
Journal: European Respiratory Journal (2015)

With the foreseen dissemination of lung cancer screening with low-dose spiral computed tomography (LDCT), a great number of subjects will come to medical attention harbouring small, indeterminate pulmonary nodules [1]. Subsolid lung nodules (SSNs), also called ground-glass opacities or ground-glass nodules (GGNs), are identified in 2–3% of subjects receiving a screening LDCT [2, 3]. Many of them have a benign aetiology and resolve spontaneously over time. However, unlike solid nodules that represent true lung cancer in a tiny fraction of patients, nonresolving SSNs are found to be histologically malignant in 30–70% of the cases [4, 5]. For this reason, they are often considered for immediate resection. Nonetheless, recent reports [6, 7] suggest that long-term observation of these patients may be appropriate. A long-term follow-up strategy may be reasonable for subsolid nodules at low risk of progression based on CT features <http://ow.ly/HasGF>
Epigenetic Profiling in Chronic Lymphocytic Leukemia Reveals Novel Methylation Targets
Authors: Laura J. Rush, Aparna Raval, Pauline Funchain, Amy J. Johnson, Lisa Smith, David M. Lucas, Melania Bembea, Te-Hui Liu, Nyla A. Heerema, Laura Rassenti, Sandya Liyanarachchi, Ramana Davuluri, John C. Byrd, Christoph Plass
Journal: Cancer Research (2004)

Abstract CpG island methylation is an epigenetic alteration that contributes to tumorigenesis by transcriptional inactivation of genes. Little is known about the overall levels of CpG island methylation in chronic lymphocytic leukemia (CLL). To provide a baseline estimate of global aberrant methylation and identify target sequences for additional investigation, we performed Restriction Landmark Genomic Scanning on 10 CLL samples. Two methylation-sensitive landmark enzymes were used (NotI and AscI), allowing assessment of over 3000 CpG islands in each sample. Tumor-derived Restriction Landmark Genomic Scanning profiles were compared with profiles from CD19-selected B cells from normal volunteers and matched normal neutrophils from 4 CLL patients. We found 2.5–8.1% (mean 4.8%) of the CpG islands in CLL samples were aberrantly methylated compared with controls, and the methylation events had a nonrandom distribution (P &amp;lt; 0.0001). Furthermore, we identified 193 aberrantly methylated sequences, of which 93% have CpG island characteristics and 90% have homology to genes or expressed sequences. One such gene, the G protein-coupled metabotropic glutamate receptor 7 (GRM7), possibly inhibits cyclic AMP signaling in the induction of apoptosis. Bisulfite sequencing of GRM7 confirmed extensive CpG island methylation, and treatment with 5-aza-2′-deoxycytidine (decitabine) resulted in up-regulated expression of several genes in vitro with concurrent cellular depletion of DNMT1 protein. Our dual-enzyme global methylation study shows that CLL is characterized by widespread nonrandom CpG island methylation similar to other tumors and provides a panel of novel methylation targets that can be used in larger studies designed to assess impact on disease progression and survival.
Questions and Answers on Design of Dual-Label Microarrays for Identifying Differentially Expressed Genes
Authors: K. Dobbin, J. H. Shih, R. Simon
Journal: JNCI Journal of the National Cancer Institute (2003)

The rapid growth in the use of microarrays has generated many questions about how to design experiments that use this technology effectively. Investigators need answers to questions about RNA sample selection, allocation of samples to arrays, robustness of design, dye bias, sample size, and statistical power to ensure that the experimental objectives are achieved. We address some common questions that arise in designing duallabel microarray experiments and provide statistical answers to these questions, focusing specifically on how to select optimal designs for the identification of differentially expressed genes.
Sudden infant death syndrome and postneonatal mortality in immigrants in England and Wales.
Authors: R. Balarajan, V. Soni Raleigh, B. Botting
Journal: BMJ (1989)

To examine ethnic differences in postneonatal mortality and the incidence of sudden infant death in England and Wales during 1982-5 records were analysed, the mother9s country of birth being used to determine ethnic group. Postneonatal mortality was highest in infants of mothers born in Pakistan (6.4/1000 live births) followed by infants of mothers born in the Caribbean (4.5) and the United Kingdom and Republic of Ireland (4.1). Crude rates were lower in infants of mothers born in India (3.9/1000), east and west Africa (3.0), and Bangladesh (2.8) than in infants of mothers born in the United Kingdom despite less favourable birth weights. Mortality ratios standardised separately for maternal age, parity, and social class were significantly higher in infants of mothers born in Pakistan and lower in those of mothers born in Bangladesh. The ratio for infants of Caribbean mothers was significantly higher when adjusted for maternal age. Ratios for infants of Indian and east African mothers did not show significant differences after standardisation. An important finding was a low incidence of sudden infant death in infants of Asian origin. This was paralleled by lower mortality from respiratory causes. During 1975-85 postneonatal mortality in all immigrant groups except Pakistanis fell to a similar or lower rate than that in the United Kingdom group; Pakistanis showed a persistent excess. During 1984-5 several immigrant groups (from the Republic of Ireland, India, west Africa, and the Caribbean) recorded an increase in postneonatal mortality. Surveillance of postneonatal mortality among ethnic communities should be continued, and research is needed to identify the causes underlying the differences.
Maximal Treadmill Exercise Electrocardiography
Authors: CARROLL M. MARTIN, DAVID R. MCCONAHAY
Journal: Circulation (1972)

Electrocardiograms were recorded during and at 2-min intervals following maximal treadmill exercise in 100 patients and were correlated with coronary arteriograms, left ventricular cineangiograms, and resting and exercise cardiac hemodynamics. The incidence and extent of exercise-induced "ischemic" S-T segment depression increased significantly ( P &lt; 0.01) with increasing extent of coronary artery disease (CAD). A criterion of abnormality of 1.0 mm or greater S-T depression most accurately predicted the presence of CAD with a specificity (true negative) of 89% and a sensitivity (true positive) of 62%. Criteria of ≧0.75 and ≧0.5 mm S-T depression offered improved sensitivities (68 and 84%, respectively) but markedly reduced specificities (78 and 57%, respectively). A significant correlation ( P &lt; 0.005) was found between increasing extent of exercise-induced S-T segment depression and the pulmonary artery wedge pressure during exercise. There were no correlations between the presence or extent of exercise-induced S-T depression and the resting or exercise pulmonary artery pressure, cardiac index, stroke-volume index, or exercise factor, or the resting left ventricular dp/dt, left ventricular end-diastolic pressure, left ventricular ejection fraction, or presence of asynergy on the left ventricular cineangiogram. The maximal treadmill exercise test provided a noninvasive method for predicting the presence and extent of significant CAD in the individual patient with chest pain. Although a normal treadmill exercise test provided little insight into the underlying resting and exercise hemodynamics, an abnormal treadmill test (≧1.0 mm S-T depression) was associated with an abnormal increase in left ventricular filling pressure with exercise in 90% of the patients.
Serial Transplantation of Urethan-Treated Mammary Nodule Outgrowth Line D1&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1972)

Urethan-treated mammary nodule outgrowths were serially transplanted in various groups of mice for 2 or more generations. The urethan-treated outgrowths differed from methylcholanthrene (MCA)-treated outgrowths in 2 ways: 1) D1 nodule outgrowths exposed to urethan produced a high incidence of tumors (83%) if left in situ, continuing to yield tumors (32%) when retransplanted into untreated mice. However, the tumor incidence decreased with successive transplant generations. 2) Urethan treatment did not alter the sensitivity of the nodule cells to hormone-mediated tumor-igenesis. The oncogenic agents, urethan and mammary tumor virus (MTV), and urethan and MCA, were applied sequentially to D1 outgrowths. The results indicated that the effects of urethan and MTV, and urethan and MCA, were additive in the induction of mammary tumors. Thus, prior exposure of the outgrowths to urethan did not alter their responsiveness to MTV or MCA. These experiments provide no evidence that urethan interacts with MTV to promote mammary tumor-igenesis in these nodule outgrowths.
MB-14 * DISCOVERING THE TREATMENT REFRACTORY BTIC POPULATION IN GROUP 3 MEDULLOBLASTOMA
Authors: David Bakhshinyan, Thusyanth Vijayakumar, Neha Garg, Branavan Manoranjan, Nicole McFarlane, Chitra Venugopal, Sheila Singh
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups: WNT, SHH, Group 3 and Group 4 of which Group 3 tumours are associated with increased chances of metastasis and poor patient outcome. Using a cell-surface marker, CD133, a subpopulation of cells with stem cell properties, termed brain tumour initiating cells (BTICs) was identified, and was further shown to drive medulloblastoma tumorigenesis in vitro and in vivo. Previous in silico analyses revealed enriched expression of many stem cell self-renewal regulatory genes in Group 3 MBs. In this work, we aim to identify and characterize the treatment-refractory BTIC population in Group 3 MBs by developing a mouse- adapted therapy treatment model that mimics the clinical treatment of MB. A mouse-adapted MB therapy model was developed using our human-mouse BTIC xenograft, in which MB cells tagged with GFP were intracranially transplanted into the frontal lobes of NOD-SCID mice. After tumour engraftment, mice assigned to receive treatment of craniospinal radiation, followed by intraperitoneal injections of chemotherapeutic drugs Vincristine, Cisplatin and Cyclophosphamide. Following enrichment of tumour cells from cultured brains, in vitro stem cell assays for self-renewal, flow characterization, and candidate gene expression profiling by NanoString were performed. Spinal cords were also harvested from mice in order to elucidate spinal dissemination of human MB cells. We found that the cells cultured from xenografts of treatment group showed an increase in self-renewal and despite evident tumour regression post-therapy, treated tumours showed an increase in expression of CD133, Sox2 and Bmi1 compared to untreated tumours. Profiling genomic changes in “treatment-responsive” tumors against those that fail therapy will generate a differential profile of the refractory BTIC, which may guide future therapeutic approaches targeting this cell, and will serve as a model for targeting such CSCs in other TIC-driven solid tumours.
Serum insulin and glucose response to graded exercise in adults. Part II. The effect of exercise conditioning.
Authors: J. A. White, A. H. Ismail, C. A. Bradley
Journal: British Journal of Sports Medicine (1978)

The effect of conditioning to severe exercise upon serum immunoreactive insulin levels (IRI) and serum glucose concentrations (GC) was studied in active and sedentary groups of middle-aged men. The responses of serum IRI and serum GC were determined during graded cycle ergometer exercise which required similar low and high relative work intensities, before (pre) and after (post) a four month physical fitness programme. Both groups demonstrated a marked decline in serum IRI during high intensity exercise from pre to post tests, and a tendency to maintain serum, GC (sedentary group) or elevate serum GC (active group) during exercise, following the conditioning programme. The data provides evidence of a bi-directional response of serum IRI and serum GC to graded exercise, with only minor modifications in the response patterns resulting from exercise conditioning.