tbuckley/cabot-search huggingface dataset:
Toxicities and Adverse Drug Reactions Experienced During Anticancer Treatment: It Is Desirable to Consider the Problem Within the International System of Pharmacovigilance
Authors: Paolo Baldo, Giulia Fornasier, Sara Francescon, Emanuela Ferrarin, Ivana Truccolo, Paolo De Paoli
Journal: Journal of Clinical Oncology (2015)

We read with much pleasure the article by Di Maio et al. 1 It is quite unusual to deal with articles reporting treatment-related toxicities as experienced and reported by patients in scientific literature.A major strength of this article is the authors' ability to share data with three sponsors.Promoters of clinical trials usually tend to emphasize, for obvious commercial reasons, their effectiveness rather than their negative implications, like adverse effects. 2,3The authors consistently discussed important issues; however, we would like to add the following considerations that may reinforce their results.
Extensive and Evolutionarily Persistent Mitochondrial tRNA Editing in Velvet Worms (Phylum Onychophora)
Authors: Romulo Segovia, Walker Pett, Steve Trewick, Dennis V. Lavrov
Journal: Molecular Biology and Evolution (2011)

Mitochondrial genomes of onychophorans (velvet worms) present an interesting problem: Some previous studies reported them lacking several transfer RNA (tRNA) genes, whereas others found that all their tRNA genes were present but severely reduced. To resolve this discrepancy, we determined complete mitochondrial DNA (mtDNA) sequences of the onychophorans Oroperipatus sp. and Peripatoides sympatrica as well as cDNA sequences from 14 and 10 of their tRNAs, respectively. We show that tRNA genes in these genomes are indeed highly reduced and encode truncated molecules, which are restored to more conventional structures by extensive tRNA editing. During this editing process, up to 34 nucleotides are added to the tRNA sequences encoded in Oroperipatus sp. mtDNA, rebuilding the aminoacyl acceptor stem, the TΨC arm, and in some extreme cases, the variable arm and even a part of the anticodon stem. The editing is less extreme in P. sympatrica in which at least a part of the TΨC arm is always encoded in mtDNA. When the entire TΨC arm is added de novo in Oroperipatus sp., the sequence of this arm is either identical or similar among different tRNA species, yet the sequences show substantial variation for each tRNA. These observations suggest that the arm is rebuilt, at least in part, by a template-independent mechanism and argue against the alternative possibility that tRNA genes or their parts are imported from the nucleus. By contrast, the 3′ end of the aminoacyl acceptor stem is likely restored by a template-dependent mechanism. The extreme tRNA editing reported here has been preserved for >140 My as it was found in both extant families of onychophorans. Furthermore, a similar type of tRNA editing may be present in several other groups of arthropods, which show a high degree of tRNA gene reduction in their mtDNA.
Suboptimal specificity of Xpert MTB/RIF among treatment-experienced patients
Authors: John Z. Metcalfe, Salome Makumbirofa, Beauty Makamure, Reggie Mutetwa, Renée A. Peñaloza, Charles Sandy, Wilbert Bara, Stanley Mungofa, Philip C. Hopewell, Peter Mason
Journal: European Respiratory Journal (2015)

The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is strongly recommended by the World Health Organization as an initial diagnostic test for treatment-experienced patients of any retreatment category [1–3]. Yet, retreatment tuberculosis (TB) suspects have been infrequently included in studies of Xpert [4], probably because current-generation PCR-based tests are unable to determine Mycobacterium tuberculosis viability [5]. Indeed, Xpert is known to frequently remain positive at the end of standard short-course therapy [6], with case reports emerging of Xpert false-positivity for up to 5 years post-treatment completion [7, 8]. Furthermore, 56% (n=3485/6285) of specificity data informing the most recent Cochrane meta-analysis [4] was derived from validation and demonstration studies [9, 10], which may be optimistic due to selection bias related to post-enrolment exclusions [7]. Not surprisingly, there have been increasing calls to clarify the guidelines for use of Xpert among treatment-experienced patients [11]. Xpert false-positivity may be common in recurrent TB. High Xpert quantitation result is unlikely to be false-positive <http://ow.ly/Ilg0F> We would like to thank Harare City Health Department (Harare, Zimbabwe) clinicians and staff for their support and assistance.
<i>IGH@</i> Translocations, <i>CRLF2</i> Deregulation, and Microdeletions in Adolescents and Adults With Acute Lymphoblastic Leukemia
Authors: Anthony V. Moorman, Claire Schwab, Hannah M. Ensor, Lisa J. Russell, Heather Morrison, Lisa Jones, Dino Masic, Bella Patel, Jacob M. Rowe, Martin Tallman, Anthony H. Goldstone, Adele K. Fielding, Christine J. Harrison
Journal: Journal of Clinical Oncology (2012)

To determine the prevalence and prognostic impact of significant acute lymphoblastic leukemia (ALL) -related genes: CRLF2 deregulation (CRLF2-d), IGH@ translocations (IGH@-t), and deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, and EBF1 in adolescents and adults.The cohort comprised 454 patients (age 15 to 60 years old) treated on the multicenter United Kingdom Acute Lymphoblastic Leukaemia Trial XII/Eastern Cooperative Oncology Group 2993 trial (UKALLXII/ECOG2993) with Philadelphia-negative B-cell precursor ALL. Fluorescent in situ hybridization and multiplex ligation-dependent probe amplification were used to detect these genetic alterations.Twenty patients (5%) had CRLF2-d (P2RY8-CRLF2, n = 7; IGH@-CRLF2, n = 13), and 36 patients (8%) harbored an IGH@-t with a different partner gene. There was little overlap between IGH@-t, CRLF2-d, and established chromosomal abnormalities. Deletions of CDKN2A/B, IKZF1, PAX5, ETV6, RB1, BTG1, or EBF1 were prevalent with 101 (33%) of 304 patients harboring one and 102 (33%) harboring two or more alterations, occurring with varying frequency in all cytogenetic subgroups. The 5-year event-free survival, relapse-free survival (RFS), and overall survival (OS) rates for the whole cohort were 40%, 55%, and 43%, respectively. Patients with CRLF2-d, IGH@-t, and IKZF1 deletions were associated with an inferior outcome in univariate but not multivariate analysis. In particular, CRLF2-d patients had a lower RFS compared with other patients (30%), whereas those with IGH@-t or IKZF1 deletions had a lower OS (27% and 35%, respectively).CRLF2-d and IGH@-t represent distinct subtypes of adolescent and adult ALL. Deletions of key B-cell differentiation and cell cycle control genes are highly prevalent but vary in frequency by cytogenetic subgroup. CRLF2-d, IGH@-t, and IKZF1 deletions are associated with poor outcome in adolescent and adult ALL.
Reply to T. Radivoyevitch et al
Authors: Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2013)

Radivoyevitch and Saunthararajah 1 propose that female sex is associated with better survival in myelodysplastic syndromes.They also point out that our randomized study of lower-dose decitabine 2 had an imbalance in sex distribution between both arms.It should be noted that this trial followed an adaptive design that resulted in early termination of the study and fewer patients in arm B (this was because of an early determination of increased response rate in arm A).Therefore, it is not unexpected that imbalances in clinical characteristics could result from such a design.Despite this and with longer follow-up (reported in the article), both arms were associated with similar outcomes, and it is therefore obvious that sex imbalance did not have an effect on the results and the conclusion of the article.The data discussed by Radivoyevitch and Saunthararajah are of interest, but at this point, circumstantial and not based on significant prospective analysis, and do not seem to be supported by our study.
Distribution of the bilbo Non-LTR Retrotransposon in Drosophilidae and its Evolution in the Drosophila obscura Species Group
Authors: David Blesa, Mónica Gandía, María J. Martínez-Sebastián
Journal: Molecular Biology and Evolution (2001)

The bilbo element is a non-LTR retrotransposon isolated from Drosophila subobscura. We conducted a distribution survey by Southern blot for 52 species of the family Drosophilidae, mainly from the obscura and melanogaster groups. Most of the analyzed species bear sequences homologous to bilbo from D. subobscura. In the obscura group, species from the same species subgroup also share similar Southern blot patterns. To investigate the phylogenetic relationship among these elements, we analyzed eight copies of a short sequence of the element from several species of the obscura group. The obtained phylogram agrees with the phylogeny of the species, which suggests vertical transmission of the element.
The Effect of Digitalis (Cedilanid) on the Mechanical and Electrical Activity of Extracted and Nonextracted Heart Muscle Preparations
Authors: H. STUTZ, E. FEIGELSON, J. EMERSON, R. J. BING
Journal: Circulation Research (1954)

The purpose of this investigation was to study the effect of Cedilanid on the mechanical and electrical activity of extracted and nonextracted heart muscle strips of dogs. The glycoside did not influence the work, the speed of contraction, or the length-resting tension relationship of extracted heart muscle. It produced changes in membrane action potentials, but none in membrane resting potentials. The problem of whether digitalis is bound to the membrane or the cell protein was investigated by temporary destruction of the cell membrane by water. The effects of cardiac glycosides on contractile proteins and on membrane activity are probably inseparable; they act through changes in ionic gradient between muscle cells and the surrounding medium.
EFFECTS OF RECOVERY TYPE ON JUDOKAS' SHORT-TERM MAXIMAL PERFORMANCES DURING A SIMULATED COMPETITION
Authors: Chtourou Hamdi, Baklouti Hana, Aloui Asma, Ismaïl Najla, Masmoudi Liwa, Chamari Karim, Chaouachi Anis, Souissi Nizar
Journal: British Journal of Sports Medicine (2013)

Background Scientific data regarding the effects of different forms of recovery on judokas' anaerobic performances during successive judo matches are lucking. Moreover, to our knowledge, no relevant studies have examined the effects of the combined-recovery (passive-active-passive) on these performances. Therefore, the present study aimed to examine the effect of three recovery modes (i.e., passive recovery, active recovery, and combined recovery) on judokas' anaerobic performances during a simulated competition. Methods Twelve male black belt judokas performed three test sessions, with one recovery type at each session [active (running at 50% of maximal-aerobic-velocity, passive, and combined-recovery (4 min passive-recovery, 7min active-recovery, and 4-min passive-recovery)]. During each session, the judokas performed the squat-jump (SJ), the countermovement-jump (CMJ), the hand-grip (HG), and the isometric-lumbar-contraction (ILC) tests before and after two 5-min judo matches separated with a 15-min recovery, and after a 15-min recovery subsequent to the second judo match. Results Performances during the SJ and CMJ, HG and ILC were higher in the combined-recovery condition compared to the passive-recovery one. Moreover, HG was higher after the combined-recovery than the active-recovery before the second combat. Besides, ILC was higher after the active-recovery compared to the passive-recovery before the second combat, and higher after the combined-recovery than the active-recovery 15-min after the second combat. Discussion/conclusions Judo is a dynamic, high-intensity-intermittent-combat-sport where the anaerobic system provides the short, quick, all-out bursts of maximal power during the match, while the aerobic system contributes to the judoka's ability to sustain effort for the total duration of the combat, to recover during the brief periods of rest or reduced effort, and to an effective recovery between matches. Therefore, active recovery could not be used between judo matches since the judokas need some minutes for muscles relaxation and to concentrate prior to the upcoming combat since judo requires tactical excellence.
Natural evolution of moderate sleep apnoea syndrome: significant progression over a mean of 17 months.
Authors: S T Pendlebury, J L Pépin, D Veale, P Lévy
Journal: Thorax (1997)

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with increased morbidity and mortality. It has remained unclear whether or not it is progressive. The evolution of OSA was examined in a retrospective case note study of 55 unselected patients of mean (SD) age 55.8 (10) years with mild to moderate disease untreated by interventional methods such as continuous positive airway pressure (CPAP) or surgery. Correlations between clinical and functional variables, upper airway anatomy, and change in disease severity were also investigated. METHODS: Patients underwent full polysomnography on two occasions (T0 and Tx) at a mean interval of 77 (50) weeks (range 17-229). In addition, upper airway imaging with computed tomographic scanning or cephalometry had been performed in 43 patients at T0. Morbidity before, during, and after the study period was assessed by questionnaire, as was smoking history and alcohol and sedative intake. RESULTS: The apnoea hypopnoea index (AHI) for the group as a whole increased from 21.8 (11.5) to 33.4 (21.3) (p = 0.0001). Using a 25% change in AHI to divide patients into worsened, stable, and improved groups showed that, although most of the patients deteriorated, 25 patients improved or remained stable. The change in AHI was not correlated with body mass index which remained stable at 29.7 (5.4) kg/m2 versus 29.7 (5.6) kg/m2. There was a trend for apnoea duration to increase. No patient reported increased alcohol consumption and only one patient reported increased use of sedatives between T0 and Tx. No correlation was found between change in AHI and age, time between recordings, anatomical measurements of the upper airway, respiratory function, oximetry, or arterial blood gas tensions. Total cardiovascular and cerebrovascular morbidity was high: hypertension (26 patients, 46%), cardiac arrhythmia (17 patients, 33%), angina (12 patients, 23%), myocardial infarction (10 patients, 19%), and stroke (10 patients, 19%). Twenty nine patients (52%) were prescribed CPAP after Tx, two of whom went on to have maxillofacial surgery. These 29 treated patients had significantly higher values of AHI at T0 and Tx and greater change in AHI than the untreated patients. CONCLUSIONS: This study shows that mild to moderate OSA has a tendency to worsen in the absence of significant weight gain and that upper airway anatomy and clinical variables do not appear to be useful in predicting progression. It follows that mild to moderate OSA justifies systematic follow up. Deterioration in AHI over a mean of 17 months led to interventional treatment in over 50% of patients in the study.
Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application
Authors: Xun Yuan, Hua Wu, Na Han, Hanxiao Xu, Qian Chu, Shiying Yu, Yuan Chen, Kongming Wu
Journal: Journal of Hematology & Oncology (2014)

Through epithelial-mesenchymal transition (EMT), cancer cells acquire enhanced ability of migration and invasion, stem cell like characteristics and therapeutic resistance. Notch signaling regulates cell-cell connection, cell polarity and motility during organ development. Recent studies demonstrate that Notch signaling plays an important role in lung cancer initiation and cross-talks with several transcriptional factors to enhance EMT, contributing to the progression of non-small cell lung cancer (NSCLC). Correspondingly, blocking of Notch signaling inhibits NSCLC migration and tumor growth by reversing EMT. Clinical trials have showed promising effect in some cancer patients received treatment with Notch1 inhibitor. This review attempts to provide an overview of the Notch signal in NSCLC: its biological significance and therapeutic application.
Tumor-Associated Antigens Produced by Mouse Mammary Tumor Cells in Artificial Capillary Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J C Hager, S Spiegelman, M Ramanarayanan, J Bausch, P M Galletti, P Calabresi
Journal: JNCI Journal of the National Cancer Institute (1982)

Mouse mammary tumor cells were cultured on a three-dimensional bundle of semipermeable hollow fibers as a prototype system for large-scale in vitro production of mammary tumor-associated antigens. Cells were seeded onto the surface of the hollow fibers that served as an artificial capillary network. The cells grew to tissue-like densities within 3 weeks, achieving the high density and three-dimensional intercellular relationships known to potentiate expression of murine mammary tumor virus (MuMTV) antigens. Significant levels of a 52,OOO-relative-molecular-weight (Mr) glycoprotein antigen of MuMTV (gp52) were detected on the cell side of the semipermeable membrane of the hollow fibers in a yield at least fiftyfold greater than that produced by monolayer cultures. Antigen could be collected from capillary cultures for 6–12 weeks, rather than days from monolayer cultures. Further, gp52 was collected in an undegraded state. Perfusates contained lesser amounts of cross-reactive antigenic species that were predominantly smaller than 50,000 Mr, which suggests that the fibers may be used to separate antigens from their degradation products. The production of nonviral, mammary tumor-associated antigens by cells on artificial capillaries was also demonstrated. Artificial capillary cell culture systems provide a means to obtain significant quantities of tumor-relevant antigens in a semipurified natural state.
Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review
Authors: P. Herbison
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> To determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome. <b>Design:</b> Systematic review of randomised controlled trials. <b>Data sources:</b> Published papers and abstracts. <b>Study selection:</b> Randomised controlled trials with anticholinergic drug treatment in one arm and placebo in another. <b>Data extraction:</b> Primary outcomes of interest were patient perceived cure or improvement in symptoms, differences in number of incontinent episodes and number of voids in 24 hours, and side effects. Secondary outcomes of interest were urodynamic measures of bladder function (volume at first contraction, maximum cystometric capacity, and residual volume) and adverse events. <b>Data synthesis:</b> 32 trials were included, totalling 6800 participants. Most trials were described as double blind but were variable in other aspects of quality. At the end of treatment, cure or improvement (relative risk 1.41, 95% confidence interval 1.29 to 1.54), differences in incontinent episodes in 24 hours (estimated mean difference 0.6, 0.4 to 0.8), number of voids in 24 hours (0.6, 0.4 to 0.8), maximum cystometric capacity (54 ml, 43 ml to 66 ml), and volume at first contraction (52 ml, 37 ml to 67 ml), were significantly in favour of anticholinergics (P&lt;0.0001 for all). Anticholinergics were associated with significantly higher residual volumes (4 ml, 1 ml to 7 ml; P=0.02) and an increased rate of dry mouth (relative risk 2.56, 2.24 to 2.92; P&lt;0.0001). Sensitivity analysis, although affected by small numbers of studies, showed little likelihood of an effect of age, sex, diagnosis, or choice of drug. <b>Conclusions:</b> Although statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies provided data on long term outcome. <h3>What is already known on this topic</h3> Anticholinergics are the first line medical treatment for overactive bladder The effectiveness of these drugs is unclear <h3>What this study adds</h3> Anticholinergics produce significant improvements in overactive bladder symptoms compared with placebo The benefits are, however, of limited clinical significance
Accumulation and persistence of hepatitis B virus core gene deletion mutants in renal transplant patients are associated with end-stage liver disease
Authors: S Günther, S Baginski, H Kissel, P Reinke, D H Krüger, H Will, H Meisel
Journal: Hepatology (1996)

In renal transplant recipients, chronic hepatitis B virus (HBV) infection often leads to cirrhosis and liver failure. In this study, we investigated whether or not in these patients viral variants would emerge despite immunosuppression, and whether they are associated with a specific course of liver disease. In a population of 552 renal transplant recipients hepatitis B 24 surface antigen (HBsAg)–positive patients were available for a 2–year follow–up. By polymerase chain reaction (PCR) and DNA sequencing, HBV genomes with deletions in the middle of the core gene (C–gene) were found in 9 out of the 24 patients. Seven of the 9 patients (group I) showed either persistent or increasing amounts of these variants; all patients had cirrhosis, and 5 died of end–stage liver disease. The viral variants emerged at least 1 year before liver failure. In 2 out of the 9 patients, the core deletion variants disappeared, and no further deterioration of the liver function was observed thereafter. In the remaining 15 patients (group II) without deletion mutants detected at any time, only 3 had cirrhosis ( P &lt; .001, group I vs. II), and none died ( P &lt; .001). Between both groups, there were no statistically significant differences in the other relevant variables that were examined. These results indicate that HBV C–gene deletion mutants can accumulate in long–term immunosuppressed patients, and that their persistence is associated with progressive liver disease. The accumulation of these variants may be caused by the development of cirrhosis or could be involved in hepatopathogenesis.
Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma
Authors: Faith E. Davies, Noopur Raje, Teru Hideshima, Suzanne Lentzsch, Gloria Young, Yu-Tzu Tai, Boris Lin, Klaus Podar, Deepak Gupta, Dharminder Chauhan, Steven P. Treon, Paul G. Richardson, Robert L. Schlossman, Gareth J. Morgan, George W. Muller, David I. Stirling, Kenneth C. Anderson
Journal: Blood (2001)