tbuckley/cabot-search huggingface dataset:
MOLECULAR (RE-)CLASSIFICATION OF CNS-PRIMITIVE NEUROECTODERMAL TUMORS
Authors: M. Kool, D. Sturm, P. A. Northcott, D. T. W. Jones, A. Korshunov, P. Lichter, S. Pfister
Journal: Neuro-Oncology (2014)

BACKGROUND: According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at a comprehensive molecular characterization of CNS-PNETs and compared our results to profiles of other brain tumor entities in order to define the biological nature of tumors diagnosed as CNS-PNETs. METHODS: A collection of 211 fresh-frozen or paraffin-embedded tumor samples with an institutional diagnosis “CNS-PNET” was profiled for genome-wide DNA methylation patterns and copy-number alterations, complemented by transcriptomic profiling of a subset (n = 71). (Epi-)genetic profiles of CNS-PNETs were compared to those of >3000 other childhood brain tumors including embryonal, astrocytic, and ependymal entities, and their respective molecular subgroups. We screened selected groups of tumors for recurrent mutations and expression of established molecular markers. RESULTS: DNA methylation and gene expression profiles showed a clear segregation of pediatric brain tumors by histological entities and molecular subgroups. Interestingly, CNS-PNET profiles showed a significant overlap with various well-defined entities, including AT/RT, ETMR, high-grade glioma, medulloblastoma, and ependymoma. When screening CNS-PNETs with profiles highly resembling other entities, hallmark genetic alterations of these, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, or mutations/deletions of the SMARCB1 locus, were frequently detected. Also, established protein markers, such as INI-1, LIN28A, and OLIG2, confirmed the reclassification of these CNS-PNETs. Strikingly, a subset (∼25%) of CNS-PNETs which could not be reclassified segregated into 3-4 distinct molecular subgroups, each with its own characteristic pattern of copy-number aberrations, DNA-methylation and gene expression. Currently, whole genome and RNA-sequencing of these distinct subgroups of CNS-PNETs is ongoing to reveal their underlying genetics. CONCLUSIONS: The correct classification of CNS-PNETs remains challenging. Based on the detection of recurrent genetic aberrations, many cases can be reliably re-classified, indicating that a significant proportion of CNS-PNETs may comprise a variety of other tumor subtypes. These findings suggest that the use of established and novel subgroups markers is needed in order to assist the histopathological evaluation of these tumors. In addition, we have identified a number of true CNS-PNET subtypes and are currently analyzing them in more detail in order to elucidate the genetics of these distinct groups. SECONDARY CATEGORY: Tumor Biology.
Yersinia arthritis: a clinical, immunological, and family study of 2 cases.
Authors: P.J Sheldon, N.S Mair, E Fox
Journal: Annals of the Rheumatic Diseases (1982)

We describe 2 patients who presented with yersinia arthritis within a period of 5 months in Leicester. Both were HLA B27 positive. Arthritis followed 2 to 3 weeks after pneumonia, abdominal pain, dysuria, and evidence of hepatic involvement in the first case, and dysuria and conjunctivitis in the second. Immunological studies showed the presence of IgM, IgG, and IgA antibodies at a significant level against Yersinia enterocolitica serotype O:3 in serum and synovial fluid, and immune complexes in the serum of the first case and synovial fluid of both. Arthropathy resolved after 16 weeks in the first case and 12 weeks in the second, the latter requiring systemic corticosteroids. Family studies revealed psoriatic spondylarthritis in the brother, and bilateral sacroiliitis in the mother of the second case. Both were HLA B27 positive. These are the fourth and fifth reported cases of yersinia arthritis in Britain. We believe the condition is probably underdiagnosed and that yersiniosis should be considered as a possibility in otherwise unexplained arthritis.
[527] THE EXTENT OF RIBAVIRIN-INDUCED HAEMOLYSIS DURING TREATMENT FOR HEPATITIS C IS UNRELATED TO ADMINISTERED DOSE, RATHER DEPENDS ON BASELINE HAEMOGLOBIN LEVEL AND DRUG ERYTHROCYTE CONCENTRATION
Authors: L. Baiocchi, C. Longhi, M. Delle Monache, L. Nosotti, A. Morrone, L.R. Conti, C. Telesca, M. Carbone, F. De Leonardis, M. Angelico
Journal: Journal of Hepatology (2007)
Axillary vs Sentinel Lymph Node Dissection for Invasive Breast Cancer
Authors: I-Chun Chen
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Confounding in Health Research
Authors: Sander Greenland, Hal Morgenstern
Journal: Annual Review of Public Health (2001)

▪ Abstract Consideration of confounding is fundamental to the design, analysis, and interpretation of studies intended to estimate causal effects. Unfortunately, the word confounding has been used synonymously with several other terms, and it has been used to refer to at least four distinct concepts. This paper provides an overview of confounding and related concepts based on a counterfactual model of causation. In this context, which predominates in nonexperimental research, confounding is a source of bias in the estimation of causal effects. Special attention is given to the history of definitions of confounding, the distinction between confounding and confounders, problems in the control of confounding, the relations of confounding to exchangeability and collapsibility, and confounding in randomized trials.
Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.
Authors: W A Hagopian, A E Karlsen, A Gottsäter, M Landin-Olsson, C E Grubin, G Sundkvist, J S Petersen, E Boel, T Dyrberg, A Lernmark
Journal: Journal of Clinical Investigation (1993)

At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy.
2Nd-Line Therapies After 1St-Line Therapy with Folfiri in Combination with Cetuximab or Bevacizumab in Patients with Kras Wild-Type Metastatic Colorectal Cancer (Mcrc)-Analysis of the Aio Krk 0306 (Fire 3)- Trial
Authors: D.P. Modest, S. Stintzing, L. Fischer von Weikersthal, T. Decker, A. Kiani, U. Vehling-Kaiser, S. Al-Batran, T. Heintges, C. Lerchenmüller, C. Kahl, G. Seipelt, F. Kullmann, M. Stauch, W. Scheithauer, S. Held, C. Giessen, A. Jung, T. Kirchner, V. Heinemann
Journal: Annals of Oncology (2014)
Spontaneous delayed recovery of perfusion and contraction after the first 5 weeks after anterior infarction. Evidence for the presence of hibernating myocardium in the infarcted area.
Authors: M Galli, C Marcassa, R Bolli, P Giannuzzi, P L Temporelli, A Imparato, P L Silva Orrego, R Giubbini, A Giordano, L Tavazzi
Journal: Circulation (1994)

BACKGROUND In patients with ventricular dysfunction caused by stunning or hibernation, it is not clear when complete recovery of the salvaged myocardium occurs after acute myocardial infarction. The purpose of this study was to determine whether a delayed recovery of perfusion and contraction continues even after the subacute phase. METHODS AND RESULTS We prospectively studied 71 consecutive male patients with first uncomplicated Q-wave anterior infarction. Resting regional blood flow distribution and contraction were assessed quantitatively 5 weeks and 7 months after the acute phase by serial sestamibi tomography and two-dimensional echocardiography. Coronary angiography also was performed in 52 patients. Overall, at 7 months there was an improvement in the perfusion defect severity (1019 +/- 811 versus 1365 +/- 821 at 5 weeks, P &lt; .001) as well as in the extent of abnormal wall motion (28 +/- 19% versus 32 +/- 15%, P &lt; .001) and left ventricular ejection fraction (53 +/- 14% versus 50 +/- 13%, P &lt; .01). Among the 68 of 71 patients showing resting perfusion defects at 5 weeks, two groups were identified: 47 (group 1) who showed a significant (beyond the reproducibility limits) 7-month reduction of the resting perfusion defect, and 21 patients (group 2) in whom the perfusion defect remained unchanged. Ejection fraction and the extent of abnormal wall motion significantly (P &lt; .01) improved in group 1 but not in group 2. Despite the presence of a comparable perfusion defect size between the two groups at 5 weeks after infarction, group 1 already showed a better regional and global ventricular function (P &lt; .05). No significant differences were found between the two groups regarding age, medical therapy, the extent of underlying coronary disease, thrombolysis in the acute phase, Thrombolysis in Myocardial Infarction grade of the infarct-related vessel, and presence of collaterals on angiography. CONCLUSIONS After anterior Q-wave infarction, the recovery of perfusion and wall motion may continue well after the subacute phase. Several patients exhibit relative hypoperfusion in viable tissue as late as 5 weeks after infarction, and a significant improvement of perfusion in the infarcted area commonly is observed between 5 weeks and 7 months. This delayed improvement of perfusion is associated with a delayed improvement of contractile function in the infarcted area after the first 5 weeks, which may continue for up to 7 months, suggesting the presence of hibernating myocardium in the infarcted area. Despite similar perfusion defect sizes, the level of regional function can be different at 5 weeks, and measurements taken around this time may not accurately estimate the eventual recovery of function.
Lowly Expressed Genes in Arabidopsis thaliana Bear the Signature of Possible Pseudogenization by Promoter Degradation
Authors: L. Yang, S. Takuno, E. R. Waters, B. S. Gaut
Journal: Molecular Biology and Evolution (2010)

Pseudogenes are defined as nonfunctional DNA sequences with homology to functional protein-coding genes, and they typically contain nonfunctional mutations within the presumptive coding region. In theory, pseudogenes can also be caused by mutations in upstream regulatory regions, appearing as open reading frames with attenuated expression. In this study, we identified 1,939 annotated protein-coding genes with little evidence of expression in Arabidopsis thaliana and characterized their molecular evolutionary characteristics. On average, this set of genes was shorter than expressed genes and evolved with a 2-fold higher rate of nonsynonymous substitutions. The divergence of upstream sequences, based on ortholog comparisons to A. lyrata, was also higher than expressed genes, suggesting that these lowly expressed genes could be examples of pseudogenization by promoter disablement, often due to transposable element insertion. We complemented our empirical study by extending the models of Force et al. (Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J. 1999. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545.) to derive the probability of promoter disablements after gene duplication.
Role of mitochondria in angiotensin II-induced reactive oxygen species and mitogen-activated protein kinase activation
Authors: G ZHANG, X LU, S KIMURA, A NISHIYAMA
Journal: Cardiovascular Research (2007)

Peptide hormone Angiotensin II (Ang II) activates NAD(P)H oxidase, via AT1 receptors leading to increased generation of reactive oxygen species (ROS), such as the superoxide anion (O2–). As an important intracellular second messenger, ROS can activate many downstream signaling molecules, including mitogen-activated protein kinases (MAPK), protein tyrosine phosphatases, protein tyrosine kinases, and transcriptional factors. Activation of these signaling cascades is highly related to risk for cardiovascular diseases. Accumulating evidence reveals that membrane-bound NAD(P)H oxidase is the main source responsible for Ang II-induced ROS generation. However, recent novel findings suggest that Ang II stimulation induces opening of mitochondrial KATP channels, depolarizes mitochondrial potential (ΔψM), and further amplifies ROS generation from mitochondria, resulting in redox-sensitive activation of MAPK. In this review, we discuss the possible mechanisms of Ang II-induced cardiac pharmacological preconditioning (PC), and focus on the role of mitochondrial KATP channels, mitochondrial ROS production, and MAPK activation in response to Ang II stimulation.
Clinical, serum cardiac troponin T and echocardiographic evaluation for prediction of late doxorubicin cardiotoxicity
Authors: E. C. Benites, M. G. Paiva, A. M. Cappellano, O. M. Felix, S. B. Marinelli, R. C. Malheiros, A. S. Petrilli
Journal: Journal of Clinical Oncology (2006)

9536 Background: To evaluate whether clinical signs or symptoms of congestive heart failure, serial assessment of systolic and diastolic cardiac function by low dose dobutamine stress echo (LDSE) and serum cardiac troponin T (cTnT) can predict doxorubicin (DOXO) cardiotoxicity. Methods: Twenty five patients with osteosarcoma enrolled in the Brazilian osteosarcoma treatment group study 2000, from january 2000 to may 2004, were studied with LDSE (&gt;5μg/kg/min) before chemotherapy, 160 mg/m 2 DOXO and after 160 mg/m 2 DOXO. cTnT were measured before and during DOXO infusion. Cardiotoxicity was defined as shortening fraction (SF) less than 30% assessed by rest echo 1 to 6 months off chemotherapy. Group A comprised those without cardiotoxicity (16 patients, 10 male, 14.3 ± 4.7 years) whereas group B included those with a SF &lt; 30% (9 patients, 6 male, 15.4 ± 3 years). Elevated serum cTnT was defined as seric levels above 0.01ng/ml. Results: Patients were submitted to a mean 3.4 LDSE and a mean of 32.5 serum cTnT. One patient (group B) presented clinical manifestation of cardiotoxicity. There was no statistical difference of elevated serum cTnT between the group B and group A (87.5% vs 46.2%; p=0,06). Left ventricular dimensions by M- MODE and transmitral Doppler inflow diastolic parameters were not significantly different between the two groups. Resting SF showed comparable values in both groups until cumulative doses of DOXO reached 160mg/m 2 , then the resting SF in group B was significant lower than group A (27% ± 2 and 34.1% ± 2, p&lt;0.01). During dobutamine infusion, SF and ΔSF (dobutamine-rest) were significantly lower in group B as compared to group A at a DOXO dose 160mg/m 2 (SF 36.1%±3,4 and ΔSF 2.1±2.3 vs. SF 45.2%±4.9 and ΔSF 9.4±3; p&lt; 0.01 and p &lt; 0.01) as well as at a DOXO dose &gt; 160mg/m 2 (30.3%±3 and 3.1±1.9 vs. 40.8%±5.9 and 7.2±4.2;p&lt;0.01 and p&lt;0.01). Conclusions: This study suggests that LDSE is more reliable than cTnT and clinical evaluation for predicting future subclinical cardiotoxicity,even at lower doxorubicin dose. No significant financial relationships to disclose.
Cardiac toxicity secondary to long term treatment with chloroquine
Authors: A CERVERA
Journal: Annals of the Rheumatic Diseases (2001)

Chloroquine is frequently used to treat systemic autoimmune diseases, such as systemic lupus erythematosus (SLE). With long term treatment, associated toxicity is well known, with retinopathy been the most common complication. Other chronic complications include skin disorders (hyperpigmentation), blood dyscrasias, corneal deposits, encephalopathy, neuropathy, myopathy, and impairment of auditory function.1 Cardiac complications, such as conduction disorders, myocardial hypertrophy, and restrictive cardiomyopathy, have also been reported in long term treatment.2-10Nevertheless, this problem is underappreciated. We describe a patient with SLE who developed a complete heart block and a restrictive cardiomyopathy owing to chronic treatment with chloroquine.

### CASE REPORT

A 64 year old woman was diagnosed with SLE and associated Sjogren's syndrome in 1988. She was treated with chloroquine for seven years (total dose 1000 g). In 1996 she presented a syncope, and a complete heart block was disclosed …
Gene Expression Profiling in Patients with Chronic Obstructive Pulmonary Disease and Lung Cancer
Authors: I-Ming Wang, Sergey Stepaniants, Yves Boie, James R Mortimer, Brian Kennedy, Mark Elliott, Shizu Hayashi, Leanna Loy, Silvija Coulter, Sandra Cervino, Jennifer Harris, Michele Thornton, Richard Raubertas, Chris Roberts, Jim C Hogg, Michael Crackower, Gary O'Neill, Peter D Paré
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Chronic obstructive lung disease (COPD) is a common and disabling lung disease for which there are few therapeutic options.We reasoned that gene expression profiling of COPD lungs could reveal previously unidentified disease pathways.Forty-eight human lung samples were obtained from tissue resected from five nonsmokers, 21 GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0, 9 GOLD stage 1, 10 GOLD stage 2, and 3 GOLD stage 3 patients. mRNA from the specimens was profiled using Agilent's Functional ID v2.0 array (Agilent, Santa Clara, CA) containing 23,720 sequences.The gene expression pattern was influenced by the percentage of the sample made up of parenchyma. Gene expression was related to forced expiratory flow between 25 and 75% of forced expiratory volume (FEF(25-75%) % predicted) revealing a signature gene set of 203 transcripts. Genes involved in extracellular matrix synthesis/degradation and apoptosis were among the up-regulated genes, whereas genes that participate in antiinflammatory responses were down-regulated. Immunohistochemistry confirmed expression of urokinase plasminogen activator (PLAU), urokinase plasminogen activator receptor (PLAUR), and thrombospondin (THBS1) by alveolar macrophages and airway epithelial cells. Genes in this pathway have been shown to be involved in the activation of transforming growth factor (TGF)-beta1 and matrix metalloproteinases and are subject to inhibition by SERPINE2. Interestingly, both TGF-beta1 and SERPINE2 have been identified as candidate genes in COPD genetic linkage and association studies.The results provide evidence that genes involved in tissue remodeling and repair are differentially regulated in the lungs of obstructed smokers and suggest that they are potential therapeutic targets. Data deposited in GEO at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE8500.
Bolus Fluorouracil and Leucovorin With Oxaliplatin as First-Line Treatment in Metastatic Colorectal Cancer
Authors: Alberto Ravaioli, Maurizio Marangolo, Enzo Pasquini, Andrea Rossi, Dino Amadori, Giorgio Cruciani, Davide Tassinari, Giovanni Oliverio, Petros Giovanis, Daniele Turci, Federica Zumaglini, Mario Nicolini, Ilaria Panzini
Journal: Journal of Clinical Oncology (2002)

PURPOSE: A phase II trial investigated the activity and toxicity of a bolus administration schedule of oxaliplatin, fluorouracil (5-FU), and leucovorin (LV) therapy in patients with untreated advanced colorectal cancer. PATIENTS AND METHODS: Forty-five patients in this multicenter, open, nonrandomized study received oxaliplatin 130 mg/m 2 on the first day of each course and 5-FU and LV 350 mg/m 2 and 20 mg/m 2 , respectively, as a daily bolus for 5 days, every 21 days, for a maximum of six courses. RESULTS: Partial responses occurred in 18 patients, giving an intent-to-treat response rate of 40.0%. Median time to response was 12.7 weeks; median duration of response was 18.4 weeks. Median progression-free survival was 5.9 months; median survival was 14 months. The independent prognostic factors for improved overall survival were good performance status and negative carcino-embryonic antigen blood level. Incidences of adverse effects were reduced after the 5-FU dose was reduced to 300 mg/m 2 . Reversible neurologic toxicity occurred in 44.4% of patients. CONCLUSION: Bolus administration of oxaliplatin, 5-FU, and LV as first-line therapy for untreated advanced colorectal cancer is efficacious and safe. In addition to a more favorable safety profile, the 300 mg/m 2 dosage offered improved dose-intensity compared with the initial dosage.
xGDB: open-source computational infrastructure for the integrated evaluation and analysis of genome features.
Authors: Shannon D Schlueter, Matthew D Wilkerson, Qunfeng Dong, Volker Brendel
Journal: Genome biology (2006)

Abstract The eXtensible Genome Data Broker (xGDB) provides a software infrastructure consisting of integrated tools for the storage, display, and analysis of genome features in their genomic context. Common features include gene structure annotations, spliced alignments, mapping of repetitive sequence, and microarray probes, but the software supports inclusion of any property that can be associated with a genomic location. The xGDB distribution and user support utilities are available online at the xGDB project website, http://xgdb.sourceforge.net/.