tbuckley/cabot-search huggingface dataset:
Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233
Authors: Raymond H. Mak, Daniel Hunt, William U. Shipley, Jason A. Efstathiou, William J. Tester, Michael P. Hagan, Donald S. Kaufman, Niall M. Heney, Anthony L. Zietman
Journal: Journal of Clinical Oncology (2014)

Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies.Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method.The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively.This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery.
A BAC-based integrated linkage map of the silkworm Bombyx mori
Authors: Kimiko Yamamoto, Junko Nohata, Keiko Kadono-Okuda, Junko Narukawa, Motoe Sasanuma, Shun-ichi Sasanuma, Hiroshi Minami, Michihiko Shimomura, Yoshitaka Suetsugu, Yutaka Banno, Kazutoyo Osoegawa, Pieter J de Jong, Marian R Goldsmith, Kazuei Mita
Journal: Genome biology (2008)

Abstract Background In 2004, draft sequences of the model lepidopteran Bombyx mori were reported using whole-genome shotgun sequencing. Because of relatively shallow genome coverage, the silkworm genome remains fragmented, hampering annotation and comparative genome studies. For a more complete genome analysis, we developed extended scaffolds combining physical maps with improved genetic maps. Results We mapped 1,755 single nucleotide polymorphism (SNP) markers from bacterial artificial chromosome (BAC) end sequences onto 28 linkage groups using a recombining male backcross population, yielding an average inter-SNP distance of 0.81 cM (about 270 kilobases). We constructed 6,221 contigs by fingerprinting clones from three BAC libraries digested with different restriction enzymes, and assigned a total of 724 single copy genes to them by BLAST (basic local alignment search tool) search of the BAC end sequences and high-density BAC filter hybridization using expressed sequence tags as probes. We assigned 964 additional expressed sequence tags to linkage groups by restriction fragment length polymorphism analysis of a nonrecombining female backcross population. Altogether, 361.1 megabases of BAC contigs and singletons were integrated with a map containing 1,688 independent genes. A test of synteny using Oxford grid analysis with more than 500 silkworm genes revealed six versus 20 silkworm linkage groups containing eight or more orthologs of Apis versus Tribolium , respectively. Conclusion The integrated map contains approximately 10% of predicted silkworm genes and has an estimated 76% genome coverage by BACs. This provides a new resource for improved assembly of whole-genome shotgun data, gene annotation and positional cloning, and will serve as a platform for comparative genomics and gene discovery in Lepidoptera and other insects.
Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in healthy volunteers
Authors: A V Emmanuel, M A Kamm, A J Roy, K Antonelli
Journal: Gut (1998)

<i>Background</i>—Stronger prokinetic agents which specifically enhance transit in different parts of the gut are required. R093877 is a novel 5-HT<sub>4</sub> agonist prokinetic compound which is chemically related to cisapride but believed to have greater effect on colonic activity. <i>Aims</i>—To evaluate the effects of R093877 on bowel function, upper and lower gut transit, visceral sensitivity, and sphincter function in healthy volunteers in a double blind, placebo controlled, crossover study. <i>Methods</i>—The study consisted of five consecutive one week periods: no drug treatment; active drug treatment with either 1 or 2 mg daily or placebo; washout; active drug or placebo; no treatment. Seventeen male subjects maintained a detailed diary of bowel function for the entire study. Orocaecal transit (breath hydrogen), whole gut transit (radio-opaque markers), and anorectal function were assessed at the end of each of the two treatment periods. Blood testing was performed to confirm compliance and for safety analysis. <i>Results—</i>One subject withdrew from the study due to side effects while on placebo. Eight subjects completed the study on 1 mg and a further eight on 2 mg. Blood testing showed non-compliance in one subject on the 2 mg dose, and he was excluded from analysis of all diary and physiological data. Treatment increased the number of stools per week (placebo versus 1 mg, 7.8 versus 13.6, p=0.003; placebo versus 2 mg, 8.9 versus 11.3, p=0.15) and the percentage of loose or watery stools (24.2% versus 61.5%, p&lt;0.04; 9.9% versus 40.0%, p&lt;0.02). Stool frequency and consistency reverted to normal immediately after treatment. Treatment shortened orocaecal and whole gut transit in all subjects on both doses. Treatment accelerated orocaecal (76 versus 51 minutes, p=0.007; 63 versus 47 minutes, p=0.07) and whole gut (38.2 versus 27.0 hours, p=0.05; 44.8 versus 24.0 hours, p&lt;0.04) transit, and decreased the number of retained markers ingested 36 hours previously (4.8 versus 1.8, p=0.016; 7.0 versus 4.3, p=0.033). Gut sensitivity to distension and electrical stimulation, and anal manometry, were unchanged. Transient headache occurred in seven subjects on R093877 and one subject had mild elevation of liver aminotransferases which resolved on drug cessation. <i>Conclusions</i>—R093877 is well tolerated by healthy subjects and has a marked and consistent effect on stool frequency and consistency, and upper gut and colonic transit. It does not affect visceral sensitivity or sphincter function. It holds promise for patients with large bowel symptoms or slow gut transit.
Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program
Authors: Kavita M. Dhodapkar, Devi Banerjee, John Connolly, Anjli Kukreja, Elyana Matayeva, Maria Concetta Veri, Jeffrey V. Ravetch, Ralph M. Steinman, Madhav V. Dhodapkar
Journal: The Journal of Experimental Medicine (2007)

The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory FcγRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fcγ receptor (FcγR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activator of transcription 1 (STAT1). FcγR-mediated STAT1 activation is rapid and requires activating FcγRs. However, this IFN response is observed without a detectable increase in the expression of type I IFNs themselves or the need to add exogenous IFNs. Induction of IFN response genes plays an important role in FcγR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcγR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcγRs may regulate IFN signaling in myeloid cells. Manipulation of FcγR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.
Reactivity, stability, and strength performance capacity in motor sports
Authors: H Baur, S Müller, A Hirschmüller, G Huber, F Mayer
Journal: British Journal of Sports Medicine (2006)

Racing drivers require multifaceted cognitive and physical abilities in a multitasking situation. A knowledge of their physical capacities may help to improve fitness and performance.To compare reaction time, stability performance capacity, and strength performance capacity of élite racing drivers with those of age-matched, physically active controls.Eight élite racing drivers and 10 physically active controls matched for age and weight were tested in a reaction and determination test requiring upper and lower extremity responses to visual and audio cues. Further tests comprised evaluation of one-leg postural stability on a two-dimensional moveable platform, measures of maximum strength performance capacity of the extensors of the leg on a leg press, and a test of force capacity of the arms in a sitting position at a steering wheel. An additional arm endurance test consisted of isometric work at the steering wheel at +30 degrees and -30 degrees where an eccentric threshold load of 30 N.m was applied. Subjects had to hold the end positions above this threshold until exhaustion. Univariate one way analysis of variance (alpha = 0.05) including a Bonferroni adjustment was used to detect group differences between the drivers and controls.The reaction time of the racing drivers was significantly faster than the controls (p = 0.004). The following motor reaction time and reaction times in the multiple determination test did not differ between the groups. No significant differences (p>0.05) were found for postural stability, leg extensor strength, or arm strength and endurance.Racing drivers have faster reaction times than age-matched physically active controls. Further development of motor sport-specific test protocols is suggested. According to the requirements of motor racing, strength and sensorimotor performance capacity can potentially be improved.
Insulin-Like Growth Factor I, IGF-Binding Protein 3, and Lung Cancer Risk in a Prospective Study of Men in China
Authors: S. J. London
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor. The major binding protein for IGF-I, insulin-like growth factor-binding protein 3 (IGFBP-3), modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor. In a prospective study of men in Shanghai, China, we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer. Methods: From 1986 to 1989, serum was collected from 18 244 men aged 45–64 years living in Shanghai without a history of cancer. We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects. Results: Among 230 case patients and 659 matched control subjects, increased IGF-I levels were not associated with increased risk of lung cancer. However, for subjects in the highest quartile relative to the lowest quartile of IGFBP-3, the odds ratio (OR) for lung cancer, adjusted for smoking and IGF-I, was 0.50 (95% confidence interval [CI] = 0.25 to 1.02). When the analysis was restricted to ever smokers (184 case patients and 344 matched control subjects), the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile, adjusted for smoking and IGF-I, was 0.41 (95% CI = 0.18 to 0.92). Conclusions: In this prospective study of Chinese men, higher serum levels of IGF-I did not increase the risk of lung cancer. However, subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer. This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor.
Prediction of trans-antisense transcripts in Arabidopsis thaliana
Authors: Huan Wang, Nam-Hai Chua, Xiu-Jie Wang
Journal: Genome biology (2006)

Natural antisense transcripts (NATs) are coding or non-coding RNAs with sequence complementarity to other transcripts (sense transcripts). These RNAs could potentially regulate the expression of their sense partner(s) at either the transcriptional or post-transcriptional level. Experimental and computational methods have demonstrated the widespread occurrence of NATs in eukaryotes. However, most previous studies only focused on cis-NATs with little attention being paid to NATs that originate in trans.We have performed a genome-wide screen of trans-NATs in Arabidopsis thaliana and identified 1,320 putative trans-NAT pairs. An RNA annealing program predicted that most trans-NATs could form extended double-stranded RNA duplexes with their sense partners. Among trans-NATs with available expression data, more than 85% were found in the same tissue as their sense partners; of these, 67% were found in the same cell as their sense partners at comparable expression levels. For about 60% of Arabidopsis trans-NATs, orthologs of at least one transcript of the pair also had trans-NAT partners in either Populus trichocarpa or Oryza sativa. The observation that 430 transcripts had both putative cis- and trans-NATs implicates multiple regulations by antisense transcripts. The potential roles of trans-NATs in inducing post-transcriptional gene silencing and in regulating alternative splicing were also examined.The Arabidopsis transcriptome contains a fairly large number of trans-NATs, whose possible functions include silencing of the corresponding sense transcripts or altering their splicing patterns. The interlaced relationships observed in some cis- and trans-NAT pairs suggest that antisense transcripts could be involved in complex regulatory networks in eukaryotes.
Transmission of the Blood Flow Pulse through the Pulmonary Arterial Tree of the Dog
Authors: NICHOLAS B. KARATZAS, MARK I.M. NOBLE, KENNETH B. SAUNDERS, MALCOLM B. MCLLROY
Journal: Circulation Research (1970)

We have made simultaneous measurements of the instantaneous flow in the main pulmonary artery using an electromagnetic flowmeter and the pulmonary capillaries using the nitrous oxide body plethysmograph method in six lightly anesthetized and spontaneously breathing dogs. We measured the transmission of the flow wave in the pulmonary arterial tree at a variety of heart rates and during alveolar hypoxia. Fourier analysis enabled us to study transmission in the intact animal in a way similar to that of imposed oscillations of flow in the isolated organ. The amplitude of the pulmonary capillary flow pulse was approximately half that in the main pulmonary artery. There was progressive decrease in amplitude from the first to the fourth harmonic in both the pulmonary arterial and pulmonary capillary flow pulses. Harmonics above the fourth were small and variable in amplitude. Transmission between pulmonary valve and capillaries was independent of heart rate. Hypoxia did not affect transmission. Assuming that the increase in resistance in this instance was due to precapillary vasoconstriction, this finding suggests that other factors may offset the effect of increase in resistance upon transmission.
A phase I study assessing the safety and pharmacokinetics of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with gemcitabine and cisplatin in patients with solid tumors
Authors: J.A. Gietema, R. Hoekstra, F.Y.F.L. de Vos, D.R.A. Uges, A. van der Gaast, H.J.M. Groen, W.J. Loos, R.A. Knight, R.A. Carr, R.A. Humerickhouse, F.A.L.M. Eskens
Journal: Annals of Oncology (2006)
Cyclooxygenase-2 Is Essential for HER2/<b> <i>neu</i> </b> to Suppress <b> <i>N</i> </b>- (4-Hydroxyphenyl)retinamide Apoptotic Effects in Breast Cancer Cells
Authors: Ann-Marie Simeone, Yu-Jiang Li, Lyle D. Broemeling, Marcella M. Johnson, Musaffe Tuna, Ana M. Tari
Journal: Cancer Research (2004)

Abstract We reported that HER2/neu reduces the sensitivity of breast cancer cells to N-(4-hydroxyphenyl)retinamide (4-HPR) by suppressing nitric oxide production. We show that HER2/neu uses Akt to induce cyclooxygenase-2 (COX-2) expression and that inhibition of Akt or COX-2 increases 4-HPR-induced apoptosis and nitric oxide production. Apoptosis induced by the 4-HPR and COX-2 inhibitor combination, although unaffected by an anti-HER2/neu antibody, was reversed by the COX-2 product prostaglandin E2, indicating that COX-2 is a major mechanism by which HER2/neu suppresses 4-HPR apoptosis in breast cancer cells. Combining 4-HPR with COX-2 inhibitors may be a novel chemopreventive strategy against HER2/neu-overexpressing breast tumors.
Infarct Tissue Heterogeneity by Magnetic Resonance Imaging Identifies Enhanced Cardiac Arrhythmia Susceptibility in Patients With Left Ventricular Dysfunction
Authors: André Schmidt, Clerio F. Azevedo, Alan Cheng, Sandeep N. Gupta, David A. Bluemke, Thomas K. Foo, Gary Gerstenblith, Robert G. Weiss, Eduardo Marbán, Gordon F. Tomaselli, João A.C. Lima, Katherine C. Wu
Journal: Circulation (2007)

The extent of the peri-infarct zone by magnetic resonance imaging (MRI) has been related to all-cause mortality in patients with coronary artery disease. This relationship may result from arrhythmogenesis in the infarct border. However, the relationship between tissue heterogeneity in the infarct periphery and arrhythmic substrate has not been investigated. In the present study, we quantify myocardial infarct heterogeneity by contrast-enhanced MRI and relate it to an electrophysiological marker of arrhythmic substrate in patients with left ventricular (LV) systolic dysfunction undergoing prophylactic implantable cardioverter defibrillator placement.Before implantable cardioverter defibrillator implantation for primary prevention of sudden cardiac death, 47 patients underwent cine and contrast-enhanced MRI to measure LV function, volumes, mass, and infarct size. A method for quantifying the heterogeneous infarct periphery and the denser infarct core is described. MRI indices were related to inducibility of sustained monomorphic ventricular tachycardia during electrophysiological or device testing. For the noninducible versus inducible patients, LV ejection fraction (30+/-10% versus 29+/-7%, P=0.79), LV end-diastolic volume (220+/-70 versus 228+/-57 mL, P=0.68), and infarct size by standard contrast-enhanced MRI definitions (P=NS) were similar. Quantification of tissue heterogeneity at the infarct periphery was strongly associated with inducibility for monomorphic ventricular tachycardia (noninducible versus inducible: 13+/-9 versus 19+/-8 g, P=0.015) and was the single significant factor in a stepwise logistic regression.Tissue heterogeneity is present and quantifiable within human infarcts. More extensive tissue heterogeneity correlates with increased ventricular irritability by programmed electrical stimulation. These findings support the hypothesis that anatomic tissue heterogeneity increases susceptibility to ventricular arrhythmias in patients with prior myocardial infarction and LV dysfunction.
Bronchodilator reversibility testing in COPD * Authors' reply
Authors: J E Cotes
Journal: Thorax (2004)

In their paper on bronchodilator reversibility testing in COPD, Calverley and colleagues1 come to the intuitively sensible conclusion that, in severe COPD, bronchodilator responsiveness is a continuous variable. However, this conclusion is based on an analysis in which the change in forced expiratory volume in 1 second …
THE NURSE'S ROLE IN INDIVIDUALIZING THE ADMISSION PROCESS IN A PSYCHIATRIC HOSPITAL
Authors: BARBARA J. ANDERSON, ROBERT C. LEONARD
Journal: American Journal of Psychiatry (1964)

We have described briefly some results of an experiment in which a patient-centered nursing approach was found to be effective in helping patients being admitted to a mental hospital. We believe admission is a crucial time for the patient, and therefore a very important time for help to be given. Since nurses traditionally play a big part in admitting patients, it is important for them to use this opportunity to give help. Moreover, we suspect that the implications of a helpful admission experience extend beyond the admission period. One of the patients who was helped by the experimental nurse illustrates this point. The study design formally ended the contact between experimental nurse and patient when the admission period was over. But during subsequent days and weeks, this patient consistently sought the nurse— sometimes telling her how well she was feeling, sometimes bringing problems. It seems logical that the patient whose first impression of the nurse was that of a concerned and helpful person would be better able to seek her assistance when she needed it throughout her hospitalization. The first helpful contact between nurse and patient facilitates subsequent helpful contacts. Thus the nurse's work is easier and the patient's care better.
Tositumomab and Iodine I 131 Tositumomab for Recurrent Indolent and Transformed B-Cell Non-Hodgkin’s Lymphoma
Authors: A.J. Davies, A.Z.S. Rohatiner, S. Howell, K.E. Britton, S.E. Owens, I.N. Micallef, D.P. Deakin, B.M. Carrington, J.A. Lawrance, S. Vinnicombe, S.J. Mather, J. Clayton, R. Foley, H. Jan, S. Kroll, M. Harris, J. Amess, A.J. Norton, T.A. Lister, J.A. Radford
Journal: Journal of Clinical Oncology (2004)

Purpose An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. Patients and Methods A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 × 10 9 /L). Forty of 41 patients received both infusions. Results Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. Conclusion High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.