tbuckley/cabot-search huggingface dataset:
Randomized Trial of Two Intravenous Schedules of the Topoisomerase I Inhibitor Liposomal Lurtotecan in Women With Relapsed Epithelial Ovarian Cancer: A Trial of the National Cancer Institute of Canada Clinical Trials Group
Authors: Graham G. Dark, A. Hilary Calvert, Robert Grimshaw, Christopher Poole, Ken Swenerton, Stan Kaye, Robert Coleman, Gordon Jayson, Tien Le, Susan Ellard, Marc Trudeau, Paul Vasey, Marta Hamilton, Terri Cameron, Emma Barrett, Wendy Walsh, Lynn McIntosh, Elizabeth A. Eisenhauer
Journal: Journal of Clinical Oncology (2005)

Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study.Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior.Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B.The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.
The Coronary Blood Flow in Pulmonary Emphysema and Cor Pulmonale
Authors: LEONARD B. ROSE, DAVID L. HOFFMAN
Journal: Circulation Research (1956)

The coronary blood flow was determined in 9 individuals with pulmonary emphysema alone and emphysema with cor pulmonale. Intracardiac pressures, cardiac output and pulmonary functions were also studied. In 8 of the 9 cases coronary blood flow was within the normal range. In one case with a high cardiac output the coronary blood flow was elevated in proportion. The presence of cor pulmonale did not appear to influence the results.
Response to: ‘Is primary Sjögren's syndrome an orphan disease? A critical appraisal of prevalence studies in Europe’ by Cornec and Chiche
Authors: Baodong Qin, Jiaqi Wang, Zaixing Yang, Yan Liang, Renqiang Zhong
Journal: Annals of the Rheumatic Diseases (2014)

Response to: 'Is primary Sjögren's syndrome an orphan disease?A critical appraisal of prevalence studies in Europe' by Cornec and Chiche We thank Divi Cornec and Laurent Chiche 1 for their valuable comments on our article. 2We think that the majority of remarks they made were reasonable and helpful for a deep understanding of the prevalence of primary Sjögren's syndrome ( pSS).Due to the great differences between a population-based study and sample survey, it is obvious that a high heterogeneity ( p<0.001 for Q statistic, I 2 =98.95%) could be observed across these articles when conducting a meta-analysis.According to the definition of a rare disease, the total prevalence rate from our study did show that pSS is not a rare disease (one case in 1644).But the prevalence rate was one case per 2304 persons when only considering a population-based study, suggesting pSS is a rare disease.Among the included studies in our paper, pSS patients from sample survey were mainly found through the questionnaire.In this process, several biases including non-response bias, coverage bias and selection bias, and so on influence the accurate prevalence rate of pSS in a defined region or a target population.However, a population-based study is often used from the administrative database or hospital medical records.Then, the population-based study could avoid these biases and provide a more accurate prevalence rate of pSS.When conducting the systematic review and meta-analysis, it is impossible to completely exclude the effect of these biases on the results.This is also a limitation of this study which was present in our article. 2Then, we analysed the differences in prevalence rate through a subgroup analysis, and the results also demonstrated that prevalence rate was greatly different between those two types of studies (43.03 cases per 100 000 inhabitants vs 282.35 cases per 100 000 inhabitants).The results from subgroup analysis
Evidence-based complementary medicine: A contradiction in terms?
Authors: E ERNST
Journal: Annals of the Rheumatic Diseases (1999)

Complementary medicine (CM) has been defined as: “diagnosis, treatment and/or prevention which complements mainstream medicine by contributing to a common whole, by satisfying a demand not met by orthodoxy or by diversifying the conceptual frameworks of medicine.”1 It comprises well over 100 different therapies, each of which has little in common with the others, and proclaims to be a veritable panacea.2 Some of the most prevalent treatments are acupuncture, aromatherapy, herbalism, homoeopathy, reflexology, and spinal manipulation (chiropractic and osteopathy). To put it mildly, CM is a notoriously controversial area.3 At the same time, CM is immensely popular and increasingly profitable (for example, MacLennan et al .4) Up to one half of the general population is using some form of CM.4 5 With rheumatological patients, this figure is even higher.6 It is therefore timely to ask whether CM is, at all, evidence based.

The apparently simple key question is, does it work? CM is often perceived as effective by those who use it. Perceived effectiveness can be viewed as being composed of specific and non-specific effectiveness,7 that is, therapeutic success can be brought about by a specific mechanism of the given treatment, for example, endorphin release after acupuncture, or by factors not directly related to the therapy itself, for example, empathy, time spent with the patient, expectation, etc. Each of the two elements can vary in size from almost 0–100% of the total therapeutic effect.7 It seems obvious therefore, that rigorous research should differentiate the non-specific from the …
Tolerogenic immunosuppression for organ transplantation
Authors: Thomas E Starzl, Noriko Murase, Kareem Abu-Elmagd, Edward A Gray, Ron Shapiro, Bijan Eghtesad, Robert J Corry, Mark L Jordan, Paulo Fontes, Tim Gayowski, Geoffrey Bond, Velma P Scantlebury, Santosh Potdar, Parmjeet Randhawa, Tong Wu Adriana Zeevi, Michael A Nalesnik, Jennifer Woodward, Amadeo Marcos, Massimo Trucco, Anthony J Demetris, John J Fung
Journal: The Lancet (2003)
IFN-γ protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism
Authors: Karl-Johan Malmberg, Victor Levitsky, Håkan Norell, Cristina Teixeira de Matos, Mattias Carlsten, Kjell Schedvins, Hodjattallah Rabbani, Alessandro Moretta, Kalle Söderström, Jelena Levitskaya, Rolf Kiessling
Journal: Journal of Clinical Investigation (2002)

IFN-γ regulates the immunogenicity of target cells by increasing their expression of HLA class I molecules. This facilitates the T cell receptor–mediated recognition by CD8+ T cells but decreases target cell sensitivity to lysis by NK cells due to engagement of inhibitory NK receptors. In this study, short-term tumor cell lines from patients with advanced ovarian carcinomas were established. We demonstrate the paradoxical finding that IFN-γ treatment of these short-term ovarian carcinoma cell lines (OVACs) resulted in resistance of tumor cells to lysis by peptide- and allospecific CD8+ T cells. Blocking experiments revealed that this phenomenon was dependent on enhanced inhibitory signalling via CD94/NKG2A receptors expressed on the effector cells. This was associated with increased expression of HLA-E mRNA and HLA-G at the protein level in IFN-γ–treated OVACs. Furthermore, pulsing of untreated OVACs with the leader sequence peptide of HLA-G protected these cells from lysis by CTLs, thus mimicking the inhibitory effect of IFN-γ. This study provides evidence that CD94/NKG2A receptors play an important role in regulating T cell activity against tumors and shows that IFN-γ modulation of target cells may shift the balance of triggering and inhibitory signals to T cells, turning off their cytolytic activity.
Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
Authors: A. Luiza Maia
Journal: Journal of Clinical Investigation (2005)

The relative roles of the types 1 and 2 iodothyronine deiodinases (D1 and D2) in extrathyroidal 3,5,3'-triiodothyronine (T3) production in humans are unknown. We calculated the rate of thyroxine (T4) to T3 conversion by intact cells transiently expressing D1 or D2 at low (2 pM), normal (20 pM), and high (200 pM) free T4 concentrations. Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2). From these calculations, we predict that in euthyroid humans, D2-generated T3 is 29 nmol/d, while that of D1-generated T3 is 15 nmol/d, from these major deiodinase-expressing tissues. The total estimated extrathyroidal T3 production, 44 nmol/d, is in close agreement with the 40 nmol T3/d based on previous kinetic studies. D2-generated T3 production accounts for approximately 71% of the peripheral T3 production in hypothyroidism, but D1 for approximately 67% in thyrotoxic patients. We also show that the intracellular D2-generated T3 has a greater effect on T3-dependent gene transcription than that from D1, which indicates that generation of nuclear T3 is an intrinsic property of the D2 protein. We suggest that impairment of D2-generated T3 is the major cause of the reduced T3 production in the euthyroid sick syndrome.
Platelet-derived growth factor receptor-<i>α</i> -associated hypereosinophilic syndrome and lymphomatoid papulosis
Authors: T. McPherson, E.W. Cowen, E. McBurney, A.D. Klion
Journal: British Journal of Dermatology (2006)

Fip1‐like 1/platelet‐derived growth factor receptor‐α (FIP1L1/PDGFRA)‐positive hypereosinophilic syndrome is a rare disorder with a poor prognosis if untreated and for which treatment with imatinib mesilate is highly effective. A 33‐year‐old man presented with recurrent papular skin lesions and marked peripheral eosinophilia. Skin biopsy revealed proliferation of CD30+ T cells consistent with lymphomatoid papulosis (LyP), whereas molecular analysis of peripheral blood mononuclear cells demonstrated the presence of the FIP1L1/PDGFRA fusion gene. As the presence of this gene has important prognostic and therapeutic implications, this report underscores the importance of molecular testing in the evaluation of patients with LyP and peripheral eosinophilia.
Disease activity–guided TNF inhibitor dose reduction was noninferior to continuing TNF inhibitors for RA flares
Authors: Francisco Ramirez-Lafita
Journal: Annals of Internal Medicine (2015)

Source Citation van Herwaarden N, van der Maas A, Minten MJ, et al. Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial. BMJ. 2015;350:h1389. 25858265
Dementia in Elderly Outpatients: A Prospective Study
Authors: ERIC B. LARSON
Journal: Annals of Internal Medicine (1984)

We prospectively studied the evaluation of dementia in 107 unselected outpatients; 83 had so-called "irreversible" dementias, including 74 who had an Alzheimer-type dementia. Fifteen patients had potentially reversible dementias, of which hypothyroidism and drug toxicity were the commonest causes. Distinguishing features of reversible dementia were shorter duration, use of more prescription drugs, and less severe dementia. Almost half of the patients had other previously unrecognized treatable medical diseases. Most diagnoses were made from patient history and physical and mental status examination. Patients with reversible dementia improved but rarely reverted to normal. Objective improvement occurred in 25 patients after treating unrecognized
Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease
Authors: Petteri Paassilta
Journal: JAMA (2001)

Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD.To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD.Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland.A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias).Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD.Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103-->Trp (arginine-->tryptophan) substitution in the alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326-->Trp (glutamine-->tryptophan) substitution in the alpha2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P =.000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold.This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.
Is Carotid Artery Stent Procedure an Alternative to Carotid Endarterctomy with Regional Anesthesia Using Selective Shunt
Authors: Ata Niyazi Ecevit, Hakki Tankut Akay, Erdal Aslım, Ali Harman, Umut Özyer, Salih Özçobanoğlu, Bahadır Gültekin, Atilla Sezgin, Sait Aşlamacı
Journal: Journal of the American College of Cardiology (2013)
Statistical Guidelines for Detecting Past Population Shifts Using Ancient DNA
Authors: T. Mourier, S. Y. W. Ho, M. T. P. Gilbert, E. Willerslev, L. Orlando
Journal: Molecular Biology and Evolution (2012)

Populations carry a genetic signal of their demographic past, providing an opportunity for investigating the processes that shaped their evolution. Our ability to infer population histories can be enhanced by including ancient DNA data. Using serial-coalescent simulations and a range of both quantitative and temporal sampling schemes, we test the power of ancient mitochondrial sequences and nuclear single-nucleotide polymorphisms (SNPs) to detect past population bottlenecks. Within our simulated framework, mitochondrial sequences have only limited power to detect subtle bottlenecks and/or fast post-bottleneck recoveries. In contrast, nuclear SNPs can detect bottlenecks followed by rapid recovery, although bottlenecks involving reduction of less than half the population are generally detected with low power unless extensive genetic information from ancient individuals is available. Our results provide useful guidelines for scaling sampling schemes and for optimizing our ability to infer past population dynamics. In addition, our results suggest that many ancient DNA studies may face power issues in detecting moderate demographic collapses and/or highly dynamic demographic shifts when based solely on mitochondrial information.
Evolutionarily Conserved Amino Acids That Control TCR-MHC Interaction
Authors: Philippa Marrack, James P. Scott-Browne, Shaodong Dai, Laurent Gapin, John W. Kappler
Journal: Annual Review of Immunology (2008)

The rules for the conserved reaction of αβ T cell receptors (TCRs) with major histocompatibility complex (MHC) proteins plus peptides are poorly understood, probably because thymocytes bearing TCRs with the strongest MHC reactivity are lost by negative selection. Thus, only TCRs with an attenuated ability to react with MHC appear on mature T cells. Also, the interaction sites between TCRs and MHC may be inherently flexible and hence difficult to spot. We reevaluated contacts between TCRs and MHC in the solved structures of their complexes with these points in mind. Relatively conserved amino acids in the TCR complementarity-determining regions (CDR) 1 and CDR2 are often used to bind exposed areas of the MHC α-helices. These areas are exposed because of small amino acids that allow somewhat flexible binding of the TCRs. The TCR amino acids involved are specific to families of variable (V) regions and to some extent different rules may govern the recognition of MHCI versus MHCII.
13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography.
Authors: J Krivokapich, G T Smith, S C Huang, E J Hoffman, O Ratib, M E Phelps, H R Schelbert
Journal: Circulation (1989)

Positron emission tomography (PET) was applied to the measurement of myocardial perfusion using the perfusion tracer 13N-labeled ammonia. 13N ammonia was delivered intravenously to 13 healthy volunteers both at rest and during supine bicycle exercise. Dynamic PET imaging was obtained in three cross-sectional planes for 10 minutes commencing with each injection. The left ventricle was divided into eight sectors, and a small region of interest was assigned to the left ventricular blood pool to obtain the arterial input function. The net extraction of 13N ammonia was obtained for each sector by dividing the tissue 13N concentration at 10 minutes by the integral of the input function from the time of injection to 10 minutes. With this approach for calculating net extractions, rest and exercise net extractions were not significantly different from each other. To obviate possible overestimation of the true 13N ammonia input function by contamination by 13N-labeled compounds other than 13N ammonia or by spillover from myocardium into blood pool, the net extractions were calculated using only the first 90 seconds of the blood and tissue time-activity curves. This approach for calculating net extractions yielded significant differences between rest and exercise, with an average ratio of exercise to rest of 1.38 +/- 0.34. Nonetheless, the increase was less than predicted from the average 2.7-2.8-fold increase in double product at peak exercise or the 1.7-fold increase in double product at 1 minute after exercise. However, when the first 90 seconds of dynamic data were fit with a two compartment tracer kinetic model, average perfusion rates of 0.75 +/- 0.43 ml/min/g at rest and 1.50 +/- 0.74 ml/min/g with exercise were obtained. This average increase in perfusion of 2.2-fold corresponded to similar average increases in double product. Thus, the noninvasive technique of PET imaging with 13N ammonia shows promise for future applications in determining absolute flows in patients with coronary artery disease.
Gone with the wind: Individual differences in heuristics and biases undermine the implication of systematic irrationality
Authors: David C. Funder
Journal: Behavioral and Brain Sciences (2000)

The target article's finding of stable and general individual differences in solving of problems in heuristics-and-biases experiments is fundamentally subversive to the Meliorist research program's attention-getting claim that human thought is “systematically irrational.” Since some people get these problems right, studies of heuristics and biases may reduce to repeated demonstrations that difficult questions are hard to solve.
Ultrasonic Characterization of the Pulmonary Venous Wall
Authors: José Angel Cabrera, Damián Sánchez-Quintana, Jerónimo Farré, Felipe Navarro, José Manuel Rubio, Fernando Cabestrero, Robert H. Anderson, Siew Yen Ho
Journal: Circulation (2002)

Pulmonary vein isolation with radiofrequency catheter ablation techniques is used to prevent recurrences of human atrial fibrillation. Visualization of the architecture at the venoatrial junction could be crucial for these ablative techniques. Our study assesses the potential for intravascular ultrasound to provide this information.We retrieved 32 pulmonary veins from 8 patients dying from noncardiac causes. We obtained cross-sectional intravascular ultrasound (IVUS) images with a 3.2F, 30-MHz ultrasound catheter at intervals on each vein. Histological cross-sections at the intervals allowed comparisons with ultrasonic images. The pulmonary venous wall at the venoatrial junction revealed a 3-layered ultrasonic pattern. The inner echogenic layer represents both endothelium and connective tissue of the media (mean maximal thickness, 1.4+/-0.3 mm). The middle hypoechogenic stratum corresponds to the sleeves of left atrial myocardium surrounding the external aspect of the venous media. This layer was thickest at the venoatrial junction (mean maximal thickness, 2.6+/-0.8 mm) and decreased toward the lung hilum. The outer echodense layer corresponds to fibro-fatty adventitial tissue (mean maximal thickness, 2.15+/-0.36 mm). We found a close agreement among the IVUS and histological measurements for maximal luminal diameter (mean difference, -0.12+/-1.3 mm) and maximal muscular thickness (mean difference, 0.17+/-0.13 mm) using the Bland and Altman method.Our experimental study demonstrates for the first time that IVUS images of the pulmonary veins can provide information on the distal limits and thickness of the myocardial sleeves and can be a valuable tool to help accurate targeting during ablative procedures.