tbuckley/cabot-search huggingface dataset:
Impact of Short-Course Preoperative Radiotherapy for Rectal Cancer on Patients' Quality of Life: Data From the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 Randomized Clinical Trial
Authors: Richard J. Stephens, Lindsay C. Thompson, Phil Quirke, Robert Steele, Robert Grieve, Jean Couture, Gareth O. Griffiths, David Sebag-Montefiore
Journal: Journal of Clinical Oncology (2010)

Purpose The Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 (MRC CR07/NCIC CTG C016) trial showed that, in patients with operable rectal cancer, short-course preoperative radiotherapy (PRE) reduced the rate of local recurrence compared with surgery followed by selective postoperative chemoradiotherapy for patients with a positive circumferential resection margin. However, the advantages of giving PRE to all patients needs to be balanced against any negative impact on patients' quality of life. Patients and Methods All 1,350 patients were asked to complete the Medical Outcomes Study Short-Form 36-item (MOS SF-36) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal 38-item (EORTC QLQ-CR38) questionnaires. A priori hypotheses related to the impact of treatment on sexual, bowel, and physical function and general health. Results Male sexual dysfunction was significantly increased following surgery (P &lt; .001), although there was no difference between treatment arms. However, a treatment difference had emerged at 6 months (PRE patients reporting significantly greater dysfunction; P = .004), which persisted out to at least 2 years (an insufficient number of female patients completed the sexual dysfunction questions to draw firm conclusions). Both treatment groups reported similar levels of decreased physical function at 3 months, but thereafter it returned to baseline levels. There was no evidence of any major changes between treatments or time points in terms of general health or bowel function, but exploratory analysis indicated a significant (P = .006 at 2 years) increase in the level of fecal incontinence with PRE. Conclusion These results from a large randomized trial using validated patient-completed questionnaires show that, for males, the main adverse effect was sexual dysfunction, and the main cause of this was surgery, but that PRE also affected sexual and some aspects of bowel functioning.
Rapid Detection of Epidermal Growth Factor Receptor Mutations in Lung Cancer by the SMart-Amplification Process
Authors: Kanako Hoshi, Hideki Takakura, Yasumasa Mitani, Kenji Tatsumi, Nobuyoshi Momiyama, Yasushi Ichikawa, Shinji Togo, Toru Miyagi, Yuki Kawai, Yasushi Kogo, Takeshi Kikuchi, Chiaki Kato, Takahiro Arakawa, Syuji Uno, Paul E. Cizdziel, Alexander Lezhava, Noburou Ogawa, Yoshihide Hayashizaki, Hiroshi Shimada
Journal: Clinical Cancer Research (2007)

Abstract Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use. Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP. Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction. Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.
Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML?
Authors: N. Timilshina, H. Breunis, J.M. Brandwein, M.D. Minden, V. Gupta, S. O'Neill, G.A. Tomlinson, R. Buckstein, M. Li, S.M.H. Alibhai
Journal: Annals of Oncology (2014)
Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study)
Authors: Jill van Aken, Lotte Heimans, Henrike Gillet-van Dongen, Karen Visser, H Karel Ronday, Irene Speyer, André J Peeters, Tom W J Huizinga, Cornelia F Allaart
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo. <h3>Methods</h3> 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)). <h3>Results</h3> 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment. <h3>Conclusions</h3> After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.
The Genomic Signature of Splicing-Coupled Selection Differs between Long and Short Introns
Authors: A. Farlow, M. Dolezal, L. Hua, C. Schlotterer
Journal: Molecular Biology and Evolution (2011)

Understanding the function of noncoding regions in the genome, such as introns, is of central importance to evolutionary biology. One approach is to assay for the targets of natural selection. On one hand, the sequence of introns, especially short introns, appears to evolve in an almost neutral manner. Whereas on the other hand, a large proportion of intronic sequence is under selective constraint. This discrepancy is largely dependent on intron length and differences in the methods used to infer selection. We have used a method based on DNA strand asymmetery that does not require comparison with any putatively neutrally evolving sequence, nor sequence conservation between species, to detect selection within introns. The strongest signal we identify is associated with short introns. This signal comes from a family of motifs that could act as cryptic 5' splice sites during mRNA processing, suggesting a mechanistic justification underlying this signal of selection. Together with an analysis of intron length and splice site strength, we observe that the genomic signature of splicing-coupled selection differs between long and short introns.
Intraprostatic Steroidogenic Enzymes – Letter: Figure 1.
Authors: Elahe Mostaghel, Peter S. Nelson, Colleen Nelson, R. Bruce Montgomery
Journal: Cancer Research (2010)

We read with interest the report by Hofland and colleagues evaluating the expression of steroidogenic enzymes in castration-recurrent prostate cancer (CRPC; ref. [1][1]). Their analysis of cell lines, xenografts, normal prostate tissue, lymph node metastases, and locally recurrent CRPC tissues
Study on relevant effects of aeroyoga on physiological parameters of youth
Authors: Benu Gupta, Mukesh Agarwal, Sunita Arora
Journal: British Journal of Sports Medicine (2010)

The purpose was to study the relevant effects of new fitness regime aeroyoga on physiological parameters of the youth. The sample subjects were confined to the youth students ageing 16–21 years of Delhi and NCR. A total of 60 subjects were chosen randomly for the study. They were divided into three groups of 20 each. One group was treated with the regime of aerobics; the second was with yogasanas and the third with aeroyoga for fitness. The aeroyoga – a complete new fitness regime was developed and implemented on controlled and experimental group in comparison with yogasana and aerobic battery for the relevance. The physiological parameters were measured at three stages that is, at resting, pre-operational and post-operational. Also, the subjective assessment was done once in between the operation and after the completion of battery. Physiological measures considered were: Wt, Ht, BMI, fat%, hip-waist ratio, HR, MHR, BMR, VO 2 max and pulse rate. Analysis of variance – statistical technique was used to study the relevant effect of aeroyoga in comparison with aerobics and yogasana. The whole statistical work deals with study of independent and interaction effects as well as mean difference in Wt, Ht, BMI, fat%, hip-waist ratio, HR, MHR, BMR, VO 2 max, pulse rate and subjective assessment of aeroyoga, aerobics and yogasana battery on active and passive youth. The result revealed the significant difference in Wt, BMI, fat%, hip-waist ratio, HR, BMR, VO 2 max, pulse rate in youth going through aeroyoga, aerobics and yogasana. Whereas there was no significant difference found in Ht and MHR. The significant difference was found in subjective assessment. Conclusions The fitness battery of aeroyoga was found to delay the onset of fatigue in comparison to other fitness battery. Aeroyoga was found to be more suitable fitness programme for the people irrespective of their physical and mental condition. Aeroyoga was found to produce maximum workout in minimum time frame when compared with other two fitness regime employed.
The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection
Authors: Hiroaki Hemmi, Osamu Takeuchi, Shintaro Sato, Masahiro Yamamoto, Tsuneyasu Kaisho, Hideki Sanjo, Taro Kawai, Katsuaki Hoshino, Kiyoshi Takeda, Shizuo Akira
Journal: The Journal of Experimental Medicine (2004)

Viral infection and stimulation with lipopolysaccharide (LPS) or double stranded RNA (dsRNA) induce phosphorylation of interferon (IFN) regulatory factor (IRF)-3 and its translocation to the nucleus, thereby leading to the IFN-β gene induction. Recently, two IκB kinase (IKK)–related kinases, inducible IκB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-β production in Toll-like receptor (TLR) signaling and viral infection. In this work, we investigated the physiological roles of these kinases by gene targeting. TBK1-deficient embryonic fibroblasts (EFs) showed dramatic decrease in induction of IFN-β and IFN-inducible genes in response to LPS or dsRNA as well as after viral infection. However, dsRNA-induced expression of these genes was residually detected in TBK1-deficient cells and intact in IKK-i–deficient cells, but completely abolished in IKK-i/TBK1 doubly deficient cells. IRF-3 activation, in response not only to dsRNA but also to viral infection, was impaired in TBK1-deficient cells. Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-β and IFN-inducible genes in both TLR-stimulated and virus-infected EFs.
ADP Acting on P2Y <sub>13</sub> Receptors Is a Negative Feedback Pathway for ATP Release From Human Red Blood Cells
Authors: Lingwei Wang, Göran Olivecrona, Matthias Götberg, Martin L. Olsson, Maria Sörhede Winzell, David Erlinge
Journal: Circulation Research (2004)

Red blood cells may regulate tissue circulation and O2 delivery by releasing the vasodilator ATP in response to hypoxia. When released extracellularly, ATP is rapidly degraded to ADP in the circulation by ectonucleotidases. In this study, we show that ADP acting on P2Y13 receptors on red blood cells serves as a negative feedback pathway for the inhibition of ATP release. mRNA of the ADP receptor P2Y13 was highly expressed in human red blood cells and reticulocytes. The stable ADP analogue 2-MeSADP decreased ATP release from red blood cells by inhibition of cAMP. The P2Y12 and P2Y13 receptor antagonist AR-C67085 (30 micromol/L), but not the P2Y1 blocker MRS2179, inhibited the effects of 2-MeSADP. At doses where AR-C67085 only blocks P2Y12 (100 nmol/L), it had no effect. AR-C67085 and the nucleotidase apyrase increased cAMP per se, indicating a constant cAMP inhibitory effect of endogenous extracellular ADP. 2-MeSADP reduced plasma ATP concentrations in an in vivo pig model. Our results indicate that the ATP degradation product ADP inhibits ATP release by acting on the red blood cell P2Y13 receptor. This negative feedback system could be important in the control of plasma ATP levels and tissue circulation.
The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors
Authors: Caroline Pabst, Holger Schirutschke, Gerhard Ehninger, Martin Bornhäuser, Uwe Platzbecker
Journal: Clinical Cancer Research (2007)

Recently, high numbers of regulatory T cells within the stem cell graft were described to be associated with less graft-versus-host disease (GVHD) after related peripheral blood stem cell transplantation (PBSCT). Studies in mice also suggest a distinct role of gamma delta TCR(+) T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and gamma delta TCR(+) T cells in human PBSCT from unrelated donors.The frequency of both T-cell subsets within the graft was analyzed in 63 patients receiving unrelated allogeneic PBSCT. The respective amounts were quantified by flow cytometry and PCR and further correlated with clinical outcome.The grafts contained a median of 11.2 x 10(6)/kg CD4(+)foxp3(+) and 9.8 x 10(6)/kg gamma delta TCR(+) T cells, respectively. Patients receiving more CD4(+)foxp3(+) cells had a lower cumulative incidence of acute GVHD II-IV (44% versus 65%, P=0.03). Interestingly, in patients who received higher concentrations of donor gamma delta TCR(+) T cells, acute GVHD II-IV was more frequent (66% versus 40%, P=0.02). In multivariate analysis, only the graft concentration of gamma delta TCR(+) T cells (P=0.002) and a positive cytomegalovirus status of the recipient (P = 0.03) were significantly associated with the occurrence of acute GVHD II-IV.Graft composition of T-cell subsets seems to affect the outcome of patients receiving allogeneic PBSCT from unrelated donors. Therefore, selective manipulation or add-back of particular subsets might be a promising strategy to reduce the incidence of GVHD.
Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study
Authors: C Warren Olanow, Karl Kieburtz, Per Odin, Alberto J Espay, David G Standaert, Hubert H Fernandez, Arvydas Vanagunas, Ahmed A Othman, Katherine L Widnell, Weining Z Robieson, Yili Pritchett, Krai Chatamra, Janet Benesh, Robert A Lenz, Angelo Antonini
Journal: The Lancet Neurology (2013)
Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization.
Authors: S Keshav, P Chung, G Milon, S Gordon
Journal: The Journal of Experimental Medicine (1991)

This study demonstrates the induction of lysozyme mRNA expression in situ in tissue macrophages (M phi) of mice following in vivo stimulation. The resting resident tissue M phi of most tissues do not contain enough lysozyme mRNA to be detected by in situ hybridization using 35S-labeled RNA probes. Following Bacille Calmette Guerin or Plasmodium yoelli infection, however, M phi recruited to liver and spleen hybridize strongly to the lysozyme probe. Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. This response is also evoked by a noninfectious agent (intravenously injected sheep erythrocytes), and is possibly the result of an early phagocytic interaction. Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. Kupffer cells are rarely lysozyme-positive. Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations.
Pyridorin in Type 2 Diabetic Nephropathy
Authors: Edmund J. Lewis, Tom Greene, Samuel Spitalewiz, Samuel Blumenthal, Tomas Berl, Lawrence G. Hunsicker, Marc A. Pohl, Richard D. Rohde, Itamar Raz, Yair Yerushalmy, Yoram Yagil, Tommy Herskovits, Robert C. Atkins, Anne T. Reutens, David K. Packham, Julia B. Lewis
Journal: Journal of the American Society of Nephrology (2011)

Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls, but whether these actions translate into renoprotective effects is unknown. In this double-blind, randomized, placebo-controlled trial, we randomly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo; Pyridorin, 150 mg twice daily; or Pyridorin, 300 mg twice daily, for 52 weeks. At baseline, the mean age ± SD was 63.9±9.5 years, and the mean duration of diabetes was 17.6±8.5 years; the mean serum creatinine level was 2.2±0.6 mg/dl, and the mean protein-to-creatinine ratio was 2973±1932 mg/g. Regarding the primary end point, a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo. However, analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function. Among patients in the lowest tertile of baseline serum creatinine concentration, treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks (0.28, 0.07, and 0.14 mg/dl for placebo, Pyridorin 150 mg, and Pyridorin 300 mg, respectively; P=0.05 for either Pyridorin dose versus placebo); there was no evidence of a significant treatment effect in the middle or upper tertiles. In conclusion, this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year, although it suggests that patients with less renal impairment might benefit.
Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis
Authors: Y Levy
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it is responsive to corticosteroids, but in certain cases it may be resistant to corticosteroid or immunosuppressive treatment, or both. <b>Objective:</b> To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. <b>Methods:</b> Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1–5 years after this treatment. <b>Results:</b> In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. <b>Conclusion:</b> IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed.
Chylothorax: a review of 18 cases.
Authors: A J Fairfax, W R McNabb, S G Spiro
Journal: Thorax (1986)

Eighteen patients who had developed a chylothorax during a 25 year period, 1955-80, were reviewed. The chylothoraces occurred as a complication of cardiothoracic surgery in 11 patients, of whom eight were children in the first decade of life. Five cases followed operations for coarctation of the aorta and two occurred as a complication of a Blalock shunt for Fallot's tetralogy. The chylothorax was evident within 48 hours of the operation in all but two patients. In seven cases a second operation was performed to prevent further chylous leakage and in two infants the thoracic duct was ligated. The remainder of the postsurgical chylothoraces responded to either continuous drainage or repeated aspiration and a low fat diet. There were no late sequelae of chylothorax following surgery. Spontaneous chylothorax was identified in seven patients and in five of these it was bilateral. Patients with spontaneous chylothorax were all adults and, despite treatment, had a poor prognosis. Three with malignant disease and two with pulmonary lymphangioleiomyomatosis had died within two years of the appearance of the chylothorax. Two patients with chronic idiopathic chylothoraces survived for more than two years and one of these developed a secondary fibrothorax.
Re: Raj Satkunasivam, Sheaumei Tsai, Sumeet Syan, et al. Robotic Unclamped “Minimal-margin” Partial Nephrectomy: Ongoing Refinement of the Anatomic Zero-ischemia Concept. Eur Urol 2015;68:705–12
Authors: Xiongbing Zu, Lin Qi, Longfei Liu
Journal: European Urology (2015)