tbuckley/cabot-search huggingface dataset:
Subsequent malignancies in children and adolescents after treatment for Hodgkin's disease.
Authors: O Beaty, M M Hudson, C Greenwald, X Luo, L Fang, J A Wilimas, E I Thompson, L E Kun, C B Pratt
Journal: Journal of Clinical Oncology (1995)

PURPOSE We assessed the cumulative risk of malignancies following treatment for Hodgkin's disease in childhood and adolescence and investigated related patient and treatment characteristics. PATIENTS AND METHODS Medical records of 499 Hodgkin's disease patients treated between 1962 and 1993 were reviewed. There were 385 adolescents (&gt; or = 10 years of age at diagnosis) and 114 preadolescents (&lt; 10 years). Most patients (n = 346) were treated with radiation plus multiagent chemotherapy, while 30 received only chemotherapy and 123 only radiation therapy. Radiation doses ranged from 20 to 42 Gy. RESULTS At a median follow-up duration of 9 years (range, 0.1 to 27.4), 25 patients have had second malignancies: 19 solid tumors, four acute nonlymphoblastic leukemias (ANLLs), 1 non-Hodgkin's lymphoma (NHL), and one chronic myeloid leukemia (CML). Three patients have had a third malignancy. The estimated cumulative risk of second malignancies increased from 1.5% at 5 years to 7.7% at 15 years. All but two of the patients with second malignancies were &gt; or = 10 years of age at initial diagnosis, which reflects the higher risk among patients treated for Hodgkin's disease as adolescents (P = .01). Second malignancies were more common among female patients (P = .0002), even when those breast cancer were excluded (P = .007), and in those treated for recurrent Hodgkin's disease (P = .02). Patients with ANLL/NHL were older at diagnosis of Hodgkin's disease than those with solid tumors, (median age, 18.3 v 13.8 years; P = .04). There was no difference between groups treated with radiation therapy alone, chemotherapy alone, or radiation plus multiagent chemotherapy. CONCLUSION Adolescents treated for Hodgkin's disease are at greater at risk of second malignancies than younger patients. Overall, adolescent females treated for recurrent Hodgkin's disease appear to be at greatest risk, while preadolescents appear to be protected from this late complication.
Transcutaneous Oxygen Tension as a Potential Predictor of Cardiovascular Events in Type 2 Diabetes
Authors: Carmine Gazzaruso, Adriana Coppola, Colomba Falcone, Chiara Luppi, Tiziana Montalcini, Elisabetta Baffero, Pietro Gallotti, Arturo Pujia, Sebastiano B. Solerte, Gabriele Pelissero, Andrea Giustina
Journal: Diabetes Care (2013)

Transcutaneous oxygen tension (TcPO2) measures tissue perfusion and is important in the management of peripheral artery disease (PAD). Ankle brachial index (ABI) is used for the diagnosis of PAD and represents a predictor of major adverse cardiovascular events (MACE), even if in diabetes its diagnostic and predictive value seems to be reduced. No study has evaluated TcPO2 as a predictor of cardiovascular events. Aim of this longitudinal study was to assess whether TcPO2 is better than ABI at predicting MACE in type 2 diabetic patients.Among 361 consecutive patients with apparently uncomplicated diabetes, 67 MACE occurred during a follow-up period of 45.8 ± 23.2 months.The percentage of both subjects with low ABI (≤ 0.9) and subjects with low TcPO2 (≤ 46 mmHg as measured by a receiver operating characteristic curve) was significantly (<0.001) greater among patients with than among those without MACEs (ABI 64.2 vs. 40.8; TcPO2 58.2 vs. 34%). The Kaplan-Meier method showed that both low ABI (Mantel log-rank test, 4.087; P = 0.043) and low TcPO2 (Mantel log-rank test, 33.748; P > 0.0001) were associated with a higher rate of MACEs. Cox regression analysis showed that low TcPO2 (hazard ratio 1.78 [95% CI 1.44-2.23]; P < 0.001) was a significant predictor of MACE, while ABI did not enter the model.This longitudinal study showed that TcPO2 may be a potential predictor of MACE among patients with uncomplicated type 2 diabetes and that its predictive value seems to be greater than that of ABI.
Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial
Authors: S. Priebe, K. Yeeles, S. Bremner, C. Lauber, S. Eldridge, D. Ashby, A. S. David, N. O'Connell, A. Forrest, T. Burns
Journal: BMJ (2013)

To test whether offering financial incentives to patients with psychotic disorders is effective in improving adherence to maintenance treatment with antipsychotics.Cluster randomised controlled trial.Community mental health teams in secondary psychiatric care in the United Kingdom.Patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder, who were prescribed long acting antipsychotic (depot) injections but had received 75% or less of the prescribed injections. We randomly allocated 73 teams with a total of 141 patients. Primary outcome data were available for 35 intervention teams with 75 patients (96% of randomised) and for 31 control teams with 56 patients (89% of randomised).Participants in the intervention group were offered £15 (€17; $22) for each depot injection over a 12 month period. Participants in the control condition received treatment as usual.The primary outcome was the percentage of prescribed depot injections given during the 12 month intervention period.73 teams with 141 consenting patients were randomised, and outcomes were assessed for 131 patients (93%). Average baseline adherence was 69% in the intervention group and 67% in the control group. During the 12 month trial period adherence was 85% in the intervention group and 71% in the control group. The adjusted effect estimate was 11.5% (95% confidence interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of ≥ 95%, which was achieved in 28% of the intervention group and 5% of the control group (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003). Although differences in clinician rated clinical improvement between the groups failed to reach statistical significance, patients in the intervention group had more favourable subjective quality of life ratings (β=0.71, 95% confidence interval 0.26 to 1.15, P=0.002). The number of admissions to hospital and adverse events were low in both groups and did not show substantial differences.Offering modest financial incentives to patients with psychotic disorders is an effective method for improving adherence to maintenance treatment with antipsychotics.Current Controlled Trials ISRCTN77769281.
Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials
Authors: Chantal Quinten, Corneel Coens, Murielle Mauer, Sylvie Comte, Mirjam AG Sprangers, Charles Cleeland, David Osoba, Kristin Bjordal, Andrew Bottomley
Journal: The Lancet Oncology (2009)
microRNA-Associated Progression Pathways and Potential Therapeutic Targets Identified by Integrated mRNA and microRNA Expression Profiling in Breast Cancer
Authors: Francesca M. Buffa, Carme Camps, Laura Winchester, Cameron E. Snell, Harriet E. Gee, Helen Sheldon, Marian Taylor, Adrian L. Harris, Jiannis Ragoussis
Journal: Cancer Research (2011)

microRNA expression profiling plays an emerging role in cancer classification and identification of therapeutic strategies. In this study, we have evaluated the benefits of a joint microRNA-mRNA analysis in breast cancer. Matched mRNA and microRNA global expression profiling was conducted in a well-annotated cohort of 207 cases with complete 10-year follow-up. Penalized Cox regression including microRNA expression, mRNA expression, and clinical covariates was used to identify microRNAs associated with distant relapse-free survival (DRFS) that provide independent prognostic information, and are not simply surrogates of previously identified prognostic covariates. Penalized regression was chosen to prevent overfitting. Furthermore, microRNA-mRNA relationships were explored by global expression analysis, and exploited to validate results in several published cohorts (n = 592 with DRFS, n = 1,050 with recurrence-free survival). Four microRNAs were independently associated with DRFS in estrogen receptor (ER)-positive (3 novel and 1 known; miR-128a) and 6 in ER-negative (5 novel and 1 known; miR-210) cases. Of the latter, miR-342, -27b, and -150 were prognostic also in triple receptor-negative tumors. Coordinated expression of predicted target genes and prognostic microRNAs strengthened these results, most significantly for miR-210, -128a, and -27b, whose targets were prognostic in meta-analysis of several cohorts. In addition, miR-210 and -128a showed coordinated expression with their cognate pri-microRNAs, which were themselves prognostic in independent cohorts. Our integrated microRNA-mRNA global profiling approach has identified microRNAs independently associated with prognosis in breast cancer. Furthermore, it has validated known and predicted microRNA-target interactions, and elucidated their association with key pathways that could represent novel therapeutic targets.
Relationship between plasma uridine and urinary urea excretion
Authors: Tuneyoshi Ka, Taku Inokuchi, Daisuke Tamada, Michio Suda, Zenta Tsutsumi, Chihiro Okuda, Asako Yamamoto, Sumio Takahashi, Yuji Moriwaki, Tetsuya Yamamoto
Journal: Metabolism (2009)
Abstract 3060: DYRK2-mediated phosphorylation of c-Jun and c-Myc is requisite for proper control of the G1/S transition
Authors: Naoe Taira, Rei Mimoto, Yoshio Miki, Kiyotsugu Yoshida
Journal: Cancer Research (2012)

Abstract Transcription factors c-Jun and c-Myc are indispensable regulators for the G1/S transition and their expressions were tightly regulated at transcriptional and post-translational levels. Dysregulation of these expressions leads to tumor development and progression. Degradation of c-Jun/c-Myc, a critical event for the G1/S transition, is triggered by sequential phosphorylations by unknown priming kinase(s) and GSK3-beta. Here we show that DYRK2 (dual-specificity tyrosine-phosphorylation-regulated kinase 2) functions as a priming kinase for c-Jun/c-Myc and modifies its expression at the by post-translational level. In the absence of priming phosphorylation, c-Jun and c-Myc escape from GSK-3-mediated sequential phosphorylation and Fbw-7-mediated ubiquitination. Therefore, depletion of DYRK2 results in aberrant expression of c-Jun and c-Myc. Furthermore, in DYRK2 knockdown cells, up-regulated c-Jun and c-Myc facilitate cell proliferation and shorten the length of the G1 phase and prompts the G1/S transition. Furthermore, DYRK2 inactivation contributes to cell proliferation and tumor progression in vitro and in vivo. Pathological analysis demonstrated that DYRK2 expression is decreased in multiple cancerous tissues. Taken together, DYRK2 controls cell cycle progression at G1/S phase via phosphorylation of c-Jun and c-Myc Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3060. doi:1538-7445.AM2012-3060
Gender Eugenics Between Medicine, Culture, and Society
Authors: Vincent Couture, Régen Drouin, Anne-Sophie Ponsot, Frédérique Duplain-Laferrière, Chantal Bouffard
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image size Acknowledgments We are grateful for the precious discussions we had with the members of the Transdisciplinary Research group in Medical Genetics and Social Sciences at Université de Sherbrooke. We thank Mrs. Naomi Levin for her precious help in editing the commentary. The work underlying this commentary was supported by the Fonds de la recherche en santé du Québec (grant FRSQ-09-10-525) to CB and RD. VC holds a studentship from the Fonds québécois de la recherche sur la société et la culture (FQRSC) and the Quebec Training Network in Perinatal Research (QTNPR). FDL holds a studentship from the Foundation of Stars. CB was a Research Scholar (junior 2 program) of the FRSQ.
Phylogenomic Analysis of Kinetoplastids Supports That Trypanosomatids Arose from within Bodonids
Authors: P. Deschamps, E. Lara, W. Marande, P. Lopez-Garcia, F. Ekelund, D. Moreira
Journal: Molecular Biology and Evolution (2010)

Kinetoplastids are a large group of free-living and parasitic eukaryotic flagellates, including the medically important trypanosomatids (e.g., Trypanosoma and Leishmania) and the widespread free-living and parasitic bodonids. Small subunit rRNA- and conserved protein-based phylogenies support the division of kinetoplastids into five orders (Prokinetoplastida, Neobodonida, Parabodonida, Eubodonida, and Trypanosomatida), but they produce incongruent results regarding their relative branching order, in particular for the position of the Trypanosomatida. In general, small subunit rRNA tends to support their early emergence, whereas protein phylogenies most often support a more recent origin from within bodonids. In order to resolve this question through a phylogenomic approach, we carried out massive parallel sequencing of cDNA from representatives of three bodonid orders (Bodo saltans -Eubodonida-, Procryptobia sorokini -Parabodonida-, and Rhynchomonas nasuta -Neobodonida-). We identified 64 well-conserved proteins shared by these species, four trypanosomatids, and two closely related outgroup species (Euglena gracilis and Diplonema papillatum). Phylogenetic analysis of a concatenated data set yielded a strongly supported tree showing the late emergence of trypanosomatids as a sister group of the Eubodonida. In addition, we identified homologues of proteins involved in trypanosomatid mitochondrial mRNA editing in the three bodonid species, suggesting that editing may be widespread in kinetoplastids. Comparison of expressed sequences from mitochondrial genes showed variability at U positions, in agreement with the existence of editing activity in the three bodonid orders most closely related to trypanosomatids (Neobodonida, Parabodonida, and Eubodonida). Mitochondrial mRNA editing appears to be an ancient phenomenon in kinetoplastids.
Different Psychophysiological and Behavioral Responses Elicited by Frustration in Pediatric Bipolar Disorder and Severe Mood Dysregulation
Authors: Brendan A. Rich, Mariana Schmajuk, Koraly E. Perez-Edgar, Nathan A. Fox, Daniel S. Pine, Ellen Leibenluft
Journal: American Journal of Psychiatry (2007)

Objective: Researchers disagree as to whether irritability is a diagnostic indicator for pediatric mania in bipolar disorder. The authors compared the behavioral and psychophysiological correlates of irritability among children with severe mood dysregulation (i.e., nonepisodic irritability and hyperarousal without episodes of euphoric mood) and narrow-phenotype bipolar disorder (i.e., a history of at least one manic or hypomanic episode with euphoric mood) as well as those with no diagnosis (i.e., healthy comparison children). Method: Subjects with severe mood dysregulation (N=21) or narrow-phenotype bipolar disorder (N=35) and comparison subjects (N=26) completed the affective Posner task, an attentional task that manipulated emotional demands and induced frustration. Mood response, behavior (reaction time and accuracy), and brain activity (event-related potentials) were measured. Results: The severe mood dysregulation and narrow-phenotype bipolar disorder groups both reported significantly more arousal than comparison subjects during frustration, but behavioral and psychophysiological performance differed between the patient groups. In the frustration condition, children with narrow-phenotype bipolar disorder had lower P3 amplitude than children with severe mood dysregulation or comparison subjects, reflecting impairments in executive attention. Regardless of emotional context, children with severe mood dysregulation had lower N1 event-related potential amplitude than comparison subjects or children with narrow-phenotype bipolar disorder, reflecting impairments in the initial stages of attention. Post hoc analyses demonstrated that the N1 deficit in children with severe mood dysregulation is associated with oppositional defiant disorder symptom severity. Conclusions: Results indicate that while irritability is an important feature of severe mood dysregulation and narrow-phenotype bipolar disorder, the pathophysiology of irritability may differ among the groups and is influenced by oppositional defiant disorder severity.
Vitamin D Receptor Activators Can Protect against Vascular Calcification
Authors: Suresh Mathew, Richard J. Lund, Lala R. Chaudhary, Theresa Geurs, Keith A. Hruska
Journal: Journal of the American Society of Nephrology (2008)

An apparent conflict exists between observational studies that suggest that vitamin D receptor (VDR) activators provide a survival advantage for patients with ESRD and other studies that suggest that they cause vascular calcification. In an effort to explain this discrepancy, we studied the effects of the VDR activators calcitriol and paricalcitol on aortic calcification in a mouse model of chronic kidney disease (CKD)-stimulated atherosclerotic cardiovascular mineralization. At dosages sufficient to correct secondary hyperparathyroidism, calcitriol and paricalcitol were protective against aortic calcification, but higher dosages stimulated aortic calcification. At protective dosages, the VDR activators reduced osteoblastic gene expression in the aorta, which is normally increased in CKD, perhaps explaining this inhibition of aortic calcification. Interpreting the results obtained using this model, however, is complicated by the adynamic bone disorder; both calcitriol and paricalcitol stimulated osteoblast surfaces and rates of bone formation. Therefore, the skeletal actions of the VDR activators may have contributed to their protection against aortic calcification. We conclude that low, clinically relevant dosages of calcitriol and paricalcitol may protect against CKD-stimulated vascular calcification.
Central sleep apnoea, pathogenesis and treatment: an overview and perspective
Authors: WA De Backer
Journal: European Respiratory Journal (1995)

The prevalence of reported sleep disturbances in a general population is high. Many of the complaints are the result of sleep-related breathing disorders, due mainly to the occurrence of obstructive and central apnoeas. Obstructive sleep apnoea is a fully described and well-recognized entity. Central sleep apnoea (CSA) however, has been poorly studied. There is accumulating evidence that central sleep apnoea should be considered as the end of a spectrum. Instability in the breathing pattern is the main underlying mechanism and is due to the interaction of many factors. Breathing during sleep is dependent on metabolic control and the activity of the respiratory muscles. Decreased chemical drive and/or failing respiratory muscle function are associated with CSA and usually also with ongoing hypoventilation during wakefulness, characterized by chronic daytime hypercapnia. Central respiratory drive can also be inhibited by upper airway reflexes. Mostly, however, CSA occurs as the hallmark of unstable breathing during sleep brought about by an overall increase in loop gain (especially in light sleep stages) and the unmasking of a CO2 threshold. Arousal following central apnoeas acts as an amplification of the instability. Micro electroencephographic (EEG) arousals are often observed as a consequence of CSA. They are responsible for sleep fragmentation and hypersomnolence during the day. The daytime hypersomnolence and complaints of awakenings during sleep in patients with CSA can be striking. CSA can occur in specific pathologies, such as chronic heart failure and (post-traumatic) brain lesions, that are associated with irregular breathing. Treatment strategies are remarkably few in number. Use of nasal ventilation and the inhalation of CO2 are mainly of theoretical interest, since patients do not often tolerate these more invasive therapies. Drug treatment, especially with acetazolamide, is easier to perform. Stimulation of upper airway reflexes, by less invasive methods, seems to be promising for the near future.
Matrix metalloproteinase-2 and myocardial oxidative stress injury: beyond the matrix
Authors: A. D. Kandasamy, A. K. Chow, M. A.M. Ali, R. Schulz
Journal: Cardiovascular Research (2009)

Matrix metalloproteinase (MMP)-2 belongs to a family of zinc-dependent proteases which are best known for their ability to proteolyse extracellular matrix proteins throughout the body, including the cardiovascular system. Increased MMP-2 activity has been demonstrated in myocardial ischaemia and reperfusion injury and the progression to congestive heart failure, with most evidence to date for its role in cardiac remodelling. Recent evidence, however, shows that MMP-2 also co-localizes with and proteolyses specific protein targets within the cardiomyocyte to cause acute, reversible contractile dysfunction, challenging the conventional wisdom on the 'extracellular matrix only' actions of this enzyme. In this review, we discuss the recent upsurge in MMP-2 research with regards to its activation by non-proteolytic pathways in the setting of enhanced oxidative stress in the heart. We will focus on the consequences of intracellular actions of MMP-2 within the cardiomyocyte and its regulation at several levels including its expression, post-translational modifications, and regulation by endogenous tissue inhibitors of metalloproteinases, caveolin, and small molecule MMP inhibitors. MMP-2 is emerging as an important signalling protease implicated in the proteolytic regulation of various intracellular proteins in myocardial oxidative stress injury.
Evidence for a Secular Trend in Age of Menarche
Authors: Grace Wyshak, Rose E. Frisch
Journal: New England Journal of Medicine (1982)

WE present data documenting a secular trend toward an earlier age of menarche in Europe and the United States in the past century. There has been recent controversy on whether such a change has taken place.1 , 2 We have reviewed 218 reports on age of menarche in Europe from 1795 to 1981, covering 220,037 individuals.3 4 5 6 The historical European data are mainly from Backman's extensive collation.3 Figure 1 and Table 1 show that in Europe the age of menarche has become earlier by two to three months per decade in the past century and a half. The greatest rate of decline, 3.2 months per decade, has . . .
Imaging Macrophage and Hematopoietic Progenitor Proliferation in Atherosclerosis
Authors: Yu-Xiang Ye, Claudia Calcagno, Tina Binderup, Gabriel Courties, Edmund J. Keliher, Gregory R. Wojtkiewicz, Yoshiko Iwamoto, Jun Tang, Carlos Pérez-Medina, Venkatesh Mani, Seigo Ishino, Camilla Bardram Johnbeck, Ulrich Knigge, Zahi A. Fayad, Peter Libby, Ralph Weissleder, Ahmed Tawakol, Shipra Dubey, Anthony P. Belanger, Marcelo F. Di Carli, Filip K. Swirski, Andreas Kjaer, Willem J.M. Mulder, Matthias Nahrendorf
Journal: Circulation Research (2015)

Local plaque macrophage proliferation and monocyte production in hematopoietic organs promote progression of atherosclerosis. Therefore, noninvasive imaging of proliferation could serve as a biomarker and monitor therapeutic intervention.