tbuckley/cabot-search huggingface dataset:
Looking for Darwin in Genomic Sequences—Validity and Success of Statistical Methods
Authors: Weiwei Zhai, Rasmus Nielsen, Nick Goldman, Ziheng Yang
Journal: Molecular Biology and Evolution (2012)

The use of codon substitution models to compare synonymous and nonsynonymous substitution rates is a widely used approach to detecting positive Darwinian selection affecting protein evolution. However, in several recent papers, Hughes and colleagues claim that codon-based likelihood-ratio tests (LRTs) are logically flawed as they lack prior hypotheses and fail to accommodate random fluctuations in synonymous and nonsynonymous substitutions Friedman and Hughes (2007) also used site-based LRTs to analyze 605 gene families consisting of human and mouse paralogues. They found that the outcome of the tests was largely determined by irrelevant factors such as the GC content at the third codon positions and the synonymous rate d(S), but not by the nonsynonymous rate d(N) or the d(N)/d(S) ratio, factors that should be related to selection. Here, we reanalyze those data. Contra Friedman and Hughes, we found that the test results are related to sequence length and the average d(N)/d(S) ratio. We examine the criticisms of Hughes and suggest that they are based on misunderstandings of the codon models and on statistical errors. Our analyses suggest that codon-based tests are useful tools for comparative analysis of genomic data sets.
Low Ca2+ reperfusion and enhanced susceptibility of the postischemic heart to the calcium paradox.
Authors: J H Kirkels, T J Ruigrok, C J Van Echteld, F L Meijler
Journal: Circulation Research (1989)

This study was designed to define the effect of postischemic low Ca2+ perfusion on recovery of high-energy phosphates, intracellular pH, and contractile function in isolated rat hearts. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to follow creatine phosphate, adenosine triphosphate, intracellular inorganic phosphate, and intracellular pH during control perfusion (15 minutes), total ischemia (30 minutes), and reperfusion (30 minutes). In Group I the perfusate [Ca2+] was 1.3 mmol/l throughout the experiment, whereas in Group II the perfusate [Ca2+] was reduced to 0.05 mmol/l during the first 10 minutes of reperfusion. Hearts from Group III were not made ischemic but were subjected to 10 minutes of low Ca2+ perfusion followed by 20 minutes of normal Ca2+ perfusion. During low Ca2+ reperfusion (Group II) recovery of high-energy phosphates and pH was significantly better than in controls (Group I). However, after reexposure to normal Ca2+, metabolic recovery was largely abolished, coronary flow was suddenly impaired, and contracture developed without any rhythmic contractions. These observations indicated the occurrence of a calcium paradox rather than postponed ischemia-reperfusion damage. On the other hand, normoxic hearts (Group III) tolerated temporary perfusion with 0.05 mmol/l Ca2+ very well with respect to left ventricular developed pressure, coronary flow, and metabolic parameters. In conclusion, postischemic low Ca2+ (0.05 mmol/l) perfusion may reduce reperfusion damage, but at the same time ischemia appears to enhance the susceptibility of the heart to the calcium paradox.
T Helper Subset Differentiation in the Absence of Invariant Chain
Authors: Daniel R. Brown, Kevin Swier, Naomi H. Moskowitz, Marisa F. Naujokas, Richard M. Locksley, Steven L. Reiner
Journal: The Journal of Experimental Medicine (1997)

The outcome of murine infection with Leishmania major is regulated by major histocompatibility complex class II–restricted T helper cells. Invariant chain-deficient (Ii −/−) mice have impaired ability to present major histocompatibility complex class II–restricted antigens, and reduced numbers of CD4+ T cells. Despite these deficits, C57BL/6 Ii −/− mice controlled L. major infection comparably to wild-type mice. As assessed by mRNA analysis and in vitro antigen restimulation for IFN-γ, Ii −/− mice had normal induction of Th1 subset differentiation even though antigen-dependent proliferation of their lymph node cells was substantially compromised. In addition, BALB/c Ii −/− mice exhibited a progressive course of infection and Th2 effector cell development that were comparable to that seen in wild-type BALB/c mice. We wished to determine whether this unexpected efficiency of T helper subset induction despite inefficient T cell stimulation could be modeled in vitro. In the presence of rIL-12 or rIL-4 naive parasite-specific transgenic T cells could mature into IFN-γ–or IL-4–secreting T helper cells, respectively, even when antigen presentation was suboptimal or antigen dose was submitogenic. These experiments demonstrate that activation of T helper cells to a threshold required for IL-2 production or proliferation is not required to achieve induction of disease-regulating T helper cell effector functions, and that pathogen-associated secondary activation signals may facilitate the full differentiation of T helper subsets during limiting presentation of antigenic peptides.
Differential Genetic and Functional Markers of Second Neoplasias in Hodgkin's Disease Patients
Authors: Yolanda Lorenzo, Mariano Provencio, Luís Lombardía, Raquel Díaz, Javier Silva, Mercedes Herrera, Jose M. García, Cristina Peña, Vanesa García, Jesús Romero, Gemma Domínguez, Félix Bonilla
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The mechanisms involved in the appearance of a second neoplasia in patients with Hodgkin's disease (HD) are probably related to the genomic damage induced by the treatments administered and its repair. Here, we searched for some constitutive molecular mechanisms that in a basal manner may influence the behavior of HD patients. Experimental Design: We aimed to evaluate with the Comet Assay whether baseline, induced, and unrepaired DNA damage differ between HD patients who did not develop a second neoplasia (HD-NST), HD patients who developed a second tumor (HD-ST), and healthy individuals; and to identify, through cDNA microarray hybridization, an expression signature of genes that could discriminate between the three groups. Results: Baseline, induced, and unrepaired DNA damage was higher in HD-ST than in HD-NST and higher in the second group than in healthy donors. The genomic approach revealed two sets of genes that discriminated between healthy subjects and patients and between the three sets of individuals. Hsp40, RAD50, TPMT, Rap2a, E2F2, EPHX2, TBX21, and BATF were validated by reverse transcription-PCR. Conclusions: Functional and genomic techniques revealed that alterations in cell cycle, repair, detoxification, and stress response pathways could be involved in the development of HD and in the occurrence of a primary second neoplasia in these patients. Both approaches may be useful as biological markers in the clinical setting.
Temozolomide in metastatic breast cancer (MBC): a phase II trial of the National Cancer Institute of Canada – Clinical Trials Group (NCIC-CTG)
Authors: M.E. Trudeau, M. Crump, D. Charpentier, L. Yelle, L. Bordeleau, S. Matthews, E. Eisenhauer
Journal: Annals of Oncology (2006)
Long‐Term Safety, Efficacy, and Quality of Life in Patients With Juvenile Idiopathic Arthritis Treated With Intravenous Abatacept for Up to Seven Years
Authors: Daniel J. Lovell, Nicolino Ruperto, Richard Mouy, Eliana Paz, Nadina Rubio‐Pérez, Clovis A. Silva, Carlos Abud‐Mendoza, Ruben Burgos‐Vargas, Valeria Gerloni, Jose A. Melo‐Gomes, Claudia Saad‐Magalhaes, J. Chavez‐Corrales, Christian Huemer, Alan Kivitz, Francisco J. Blanco, Ivan Foeldvari, Michael Hofer, Hans‐Iko Huppertz, Chantal Job Deslandre, Kirsten Minden, Marilynn Punaro, Alan J. Block, Edward H. Giannini, Alberto Martini
Journal: Arthritis & Rheumatology (2015)

The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease-modifying antirheumatic drugs were previously established in a phase III study that included a 4-month open-label lead-in period, a 6-month double-blind withdrawal period, and a long-term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient-reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup.Patients enrolled in the phase III trial could enter the open-label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double-blind period.One hundred fifty-three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient-years) of adverse events decreased during the LTE phase (433.61 events during the short-term phase [combined lead-in and double-blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time.Long-term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality-of-life benefits in patients with JIA.
Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study
Authors: Jesper Hallas, Michael Dall, Alin Andries, Birthe Søgaard Andersen, Claus Aalykke, Jane Møller Hansen, Morten Andersen, Annmarie Touborg Lassen
Journal: BMJ (2006)

To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population.Population based case-control study.Funen County, Denmark (population 470,000).1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and sex matched controls.Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment.Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population.Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.
Violence and Women's Mental Health: The Impact of Physical, Sexual, and Psychological Aggression
Authors: Carol E. Jordan, Rebecca Campbell, Diane Follingstad
Journal: Annual Review of Clinical Psychology (2010)

The reach of violence against women (VAW) has been profoundly felt by women across the United States and around the globe. VAW has been documented for decades as a legal and social justice problem, but as illuminated in this review, it is also a substantial mental health concern. A full understanding of the phenomenon must include discussion of how often it occurs, in what forms, and to whom. This review defines violence against women in its variant forms and examines the literature on the mental health effects associated with these abuse experiences. The effectiveness of the mental health system's response to the complex needs of women suffering battering, rape, stalking, and psychological aggression is also examined. The future of research and the important role of the discipline of psychology in the future of this field of study are discussed.
Discriminative Validity and Clinical Utility of an Abuse-Neglect Interview for Adolescents With Conduct and Substance Use Problems
Authors: Thomas J. Crowley, Susan K. Mikulich, Kristen M. Ehlers, Shannon K. Hall, Elizabeth A. Whitmore
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Many youths with conduct and substance use problems experience abuse and neglect. A valid measure of the severity of abuse-neglect events could facilitate research and clinical care. The authors' goal was to examine the discriminative validity, clinical utility, and severity correlations of the Colorado Adolescent Rearing Inventory, a structured, 20–45-minute abuse-neglect interview in the assessment of adolescents with conduct and substance use problems. METHOD: Ninety-eight adolescent patients with conduct and substance use problems and 102 comparison subjects (about 40% of the subjects in each group were female) completed the Colorado Adolescent Rearing Inventory, the Diagnostic Interview Schedule for Children, and the Composite International Diagnostic Interview—Substance Abuse Module. RESULTS: Although the subjects were advised that reports of abuse-neglect would be communicated to child welfare agencies, nearly two-thirds of the patients with conduct and substance use problems endorsed items indicating probable abuse-neglect, compared with about a third of the comparison subjects, a highly significant difference. Clinicians judged that 68%–80% of the cases of the patients and comparison subjects who endorsed such items warranted reporting to child welfare agencies. Scores on the Colorado Adolescent Rearing Inventory correlated significantly with severity of substance involvement, conduct disorder, and major depression. Compared to males, significantly more females (including 15% of comparison females) reported sexual abuse. Patients were significantly more likely than comparison subjects to attribute adverse life effects to their reported abuse-neglect experiences. CONCLUSIONS: Colorado Adolescent Rearing Inventory scores revealed many cases of serious abuse-neglect, generated many reports to child welfare agencies, demonstrated discriminative validity, correlated with clinical measures, and reflected important gender differences. The Colorado Adolescent Rearing Inventory can contribute to clinical evaluation and research involving youths with conduct and substance use problems.
The Shame of the States
Authors: Albert Deutsch
Journal: JAMA (1949)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Raising the awareness: projecting the future burden of COPD with the BOLD model
Authors: M. Rutten-van Molken
Journal: European Respiratory Journal (2009)

ot so long ago, cost-of-illness studies were criticised for mainly estimating the annual costs of a disease in retrospect, without paying attention to trends in costs and the return on the investments in terms of health benefits.From the time when we began developing models that can simulate the future burden and costs of a disease, we recognised the importance of cost-of-illness studies for providing insight into future healthcare needs and planning purposes.Providing this insight is one of the goals of the Burden of Obstructive Lung Disease (BOLD) project.The BOLD project aims to measure the prevalence of chronic obstructive pulmonary disease (COPD) among the population aged o40 yrs, its risk factors and its impact on quality of life, activity limitation, respiratory symptoms and use of healthcare services in various countries around the world, using a standardised protocol that includes spirometry [1, 2].Among the primary objectives of the BOLD initiative was the development of a COPD health economic model to make projections of the burden of COPD in the future.In the current issue of the European Respiratory Journal, NIELSEN et al. [3] have used this model to estimate the current and future costs of COPD in Iceland and Norway over a 10-and 20-yr period.These are the first cost-of-illness data for COPD in these countries.
Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients
Authors: Koji Kurose, Yoshihiro Ohue, Hisashi Wada, Shinsuke Iida, Takashi Ishida, Takashi Kojima, Toshihiko Doi, Susumu Suzuki, Midori Isobe, Takeru Funakoshi, Kazuhiro Kakimi, Hiroyoshi Nishikawa, Heiichiro Udono, Mikio Oka, Ryuzo Ueda, Eiichi Nakayama
Journal: Clinical Cancer Research (2015)

Abstract Purpose: FoxP3+ Tregs inhibit immune responses against tumors. KW-0761 is a humanized anti-human CCR4 monoclonal antibody (mAb) that has antibody-dependent cellular cytotoxicity activity. Depletion of CCR4-expressing FoxP3+ CD4 Tregs by KW-0761 infusion was investigated in solid cancer patients. Experimental Design: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and 3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte subpopulations, including Tregs, and induction of immune responses were analyzed. Results: The results showed that KW-0761 infusion in a dose range between 0.1 mg/kg and 1.0 mg/kg was safe and well tolerated. No dose-limiting toxicity was observed. Four of 10 patients showed stable disease during treatment and were long survivors. The monitoring of FoxP3+ Tregs in the peripheral blood mononuclear cells during treatment indicated efficient depletion of those cells, even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T cells and CD8 T cells was limited, whereas a significant reduction was observed with Th 2 and Th 17 CD4 T cells. Immune responses to cancer/testis (CT) antigens and an autoantibody response to thyroid peroxidase were observed in some patients. Conclusions: The findings showed Tregs depletion and the possible occurrence of an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete FoxP3+ Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is a promising approach to augment immune responses. Clin Cancer Res; 21(19); 4327–36. ©2015 AACR.
Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients
Authors: M Majori, I Vachier, P Godard, M Farce, J Bousquet, P Chanez
Journal: European Respiratory Journal (1998)

Reactive oxygen species play an important role in promoting inflammation. Blood monocytes have been described to release higher amounts of superoxide anion in uncontrolled and untreated asthmatics. Corticosteroids are widely used in asthma, but little is known about their molecular mechanism of action. The aim of our study was to analyse the ex vivo effect of corticosteroid treatments on superoxide anion release by blood monocytes. Superoxide anion release was measured by a spectrophotometric method based on the superoxide dismutase (SOD) -inhibitable reduction of ferricytochrome C by blood monocytes from untreated patients and asthmatics treated with i.v., inhaled and oral corticosteroids. Monocytes from uncontrolled and untreated asthmatics, released high amounts of superoxide anions. After short-term treatment with i.v., corticosteroids, this release was found to decrease significantly (1.410 versus 0.340 nM, p&lt;0.05). Cells from asthmatics who had undergone long-term treatment with inhaled or oral steroids presented low amounts of superoxide anion production, with a significant difference as compared to untreated asthmatics (0.375 nM p&lt;0.01 and 0.620 nM p&lt;0.02 respectively). In general, patients with controlled asthma (treated with short-term oral steroids, or with long-term inhaled steroids) released lesser amounts of superoxide anion than uncontrolled and untreated asthmatics. In the case of steroid-dependent asthmatics there was no difference between patients with a controlled or uncontrolled disease.
Improved disease-free survival with epirubicin-based chemoendocrine adjuvant therapy compared with tamoxifen alone in one to three node-positive, estrogen-receptor-positive, postmenopausal breast cancer patients: results of French Adjuvant Study Group 02 and 07 trials
Authors: M. Namer, P. Fargeot, H. Roché, M. Campone, P. Kerbrat, P. Romestaing, A. Monnier, E. Luporsi, P. Montcuquet, J. Bonneterre
Journal: Annals of Oncology (2005)
Mediterranean Diet Reduces the Adverse Effect of the <i>TCF7L2</i>-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence
Authors: Dolores Corella, Paula Carrasco, Jose V. Sorlí, Ramón Estruch, Jesús Rico-Sanz, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, M. Isabel Covas, Oscar Coltell, Fernando Arós, José Lapetra, Lluís Serra-Majem, Valentina Ruiz-Gutiérrez, Julia Warnberg, Miquel Fiol, Xavier Pintó, Carolina Ortega-Azorín, Miguel Ángel Muñoz, J. Alfredo Martínez, Enrique Gómez-Gracia, José I. González, Emilio Ros, José M. Ordovás
Journal: Diabetes Care (2013)

Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.
The Methods of Comparative Effectiveness Research
Authors: Harold C. Sox, Steven N. Goodman
Journal: Annual Review of Public Health (2012)

This review describes methods used in comparative effectiveness research (CER). The aim of CER is to improve decisions that affect medical care at the levels of both policy and the individual. The key elements of CER are (a) head-to-head comparisons of active treatments, (b) study populations typical of day-to-day clinical practice, and (c) a focus on evidence to inform care tailored to the characteristics of individual patients. These requirements will stress the principal methods of CER: observational research, randomized trials, and decision analysis. Observational studies are especially vulnerable because they use data that directly reflect the decisions made in usual practice. CER will challenge researchers and policy makers to think deeply about how to extract more actionable information from the vast enterprise of the daily practice of medicine. Fortunately, the methods are largely applicable to research in the public health system, which should therefore benefit from the intense interest in CER.