tbuckley/cabot-search huggingface dataset:
Detecting over-age players using wrist MRI: science partnering with sport to ensure fair play
Authors: Jiri Dvorak
Journal: British Journal of Sports Medicine (2009)

Detecting the presence of over-age players in age-related tournaments has been a difficult challenge for many sports organisations. “Age-doping” is a form of cheating that involves falsification of information about the age of a player to gain advantage in the sport. This clearly contradicts the ethics of sport and fair play.

Until now, the age of competitors has generally been proven by official documents such as birth certificates. In some regions of the world, however, births are registered at police stations or rural health clinics, or by village elders. Since births do not take place at established hospitals, their registration is often delayed because of cultural, religious and climatic reasons. At times, the large distance between a place of residence and a registration “office” can mean days of travel (and hence delay). Thus, the official “birth certificate” may not reflect the actual date of birth.

In addition …
The Vav Binding Site (Y315) in ZAP-70 Is Critical for Antigen Receptor–mediated Signal Transduction
Authors: Jun Wu, Qihong Zhao, Tomohiro Kurosaki, Arthur Weiss
Journal: The Journal of Experimental Medicine (1997)

Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently phosphorylate numerous intracellular substrates, including the 95-kD protooncogene product Vav. Vav is essential for both T and B cell development and T and B cell antigen receptor–mediated signal transduction. After receptor ligation, Vav associates with phosphorylated Syk and ZAP-70 PTKs, an interaction that depends upon its SH2 domain. Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav– ZAP-70 interaction. Moreover, the Y315 mutation impaired the function of ZAP-70 in antigen receptor signaling. Surprisingly, this mutation also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav, SLP-76, and Shc. These data demonstrate that the Vav binding site in ZAP-70 plays a critical role in antigen receptor–mediated signal transduction.
Abnormal Coronary Vasomotion as a Prognostic Indicator of Cardiovascular Events in Women
Authors: Gregory O. von Mering, Christopher B. Arant, Timothy R. Wessel, Susan P. McGorray, C. Noel Bairey Merz, Barry L. Sharaf, Karen M. Smith, Marian B. Olson, B. Delia Johnson, George Sopko, Eileen Handberg, Carl J. Pepine, Richard A. Kerensky
Journal: Circulation (2004)

Coronary vascular dysfunction has been linked to atherosclerosis and adverse cardiovascular outcomes in men, but these relationships have not been firmly established in women.As part of the Women's Ischemia Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood Institute, 163 women referred for clinically indicated coronary angiography underwent coronary reactivity assessment with quantitative coronary angiography and intracoronary Doppler flow before and after intracoronary administration of acetylcholine, adenosine, and nitroglycerin and were then followed up for clinical outcomes. History of hypertension was present in 61%, dyslipidemia in 54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy-five percent had no or only mild epicardial coronary artery disease (CAD). Over a median follow-up of 48 months, events occurred in 58 women. On bivariate analysis, women with an event had significantly less change in coronary cross-sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator response to acetylcholine had less time free from cardiovascular events (P=0.004). In multivariable analysis, after controlling for age, hypertension, diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with acetylcholine (P=0.001) independently predicted events. When the outcome was restricted to only death, myocardial infarction, congestive heart failure, and stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006).In women in this study, impaired coronary vasomotor response to acetylcholine was independently linked to adverse cardiovascular outcomes regardless of CAD severity.
Preserving Fertility in Cancer Patients
Authors: A. Azvolinsky
Journal: JNCI Journal of the National Cancer Institute (2012)

F our years ago, Alice Crisci was diagnosed with stage I breast cancer at age 31. She immediately brought up fertility preservation with her oncologist, who told her there was a 50% chance the chemotherapy treatment for breast cancer would leave her infertile. “I knew if they told me there was a 2% chance, I would have still wanted to pursue fertility preservation,” said Crisci. She quickly learned that fertility preservation is expensive and that insurance typically does not cover the cost of the procedures and tests. When she did not qualify for fi nancial aid through Fertile Hope — a nonprofi t that helps cancer patients at risk for infertility — she put the $20,000 fertility preservation bill on her credit card. “I walked out of the clinic, thinking, ‘This must be why I got cancer. I am going to raise money so that other women don ’ t have to put this on their credit cards. ’ ” Three weeks after her cancer diagnosis, Crisci started a nonprofi t organization to help women with cancer preserve their fertility. “My experience echoes the experience of all the patients that I connect with and help,” Crisci said. Oncologists are much more likely to have the fertility preservation conversation with a younger female patient now than a few years ago. Still, few young women are taking the steps to preserve their fertility before undergoing toxic cancer treatment, according to a study published March 26 in Cancer. The research also shows that much more needs to be done to provide effective counseling on fertility preservation for women of reproductive age who have a cancer diagnosis.
THE ROLE OF THE PLATELET IN THE GENERALIZED SHWARTZMAN REACTION
Authors: William Margaretten, Donald G. McKay
Journal: The Journal of Experimental Medicine (1969)

Rabbits were injected with an antiplatelet serum to produce selective thrombocytopenia without inducing a significant alteration of their leukocyte counts. Thrombocytopenic levels persisted for 8 hr after the injection of platelet antiserum. During this time, the generalized Shwartzman reaction could not be provoked with the second injection of endotoxin. Since platelet phospholipid is required for the formation of plasma thromboplastin, the results indicate that platelets are essential to the evolution of the generalized Shwartzman reaction and endotoxin triggers the intrinsic rather than the extrinsic clotting system to elicit the lesions.
Determinants and prediction of transmural myocardial perfusion.
Authors: J I Hoffman
Journal: Circulation (1978)

The vulnerability of subendocardial muscle to ischemic damage is due primarily to the greater risk of under- perfusion.Recent studies of coronary autoregulation have shown that as myocardial oxygen needs increase beyond the ability of coronary blood flow to supply oxygen, maximal vasodilatation occurs earliest in subendocardial vessels; any further imbalance then causes subendocardial ischemia, since no further compensatory vasodilatation is possible.In animal experiments relative subendocardial perfusion (the ratio of flow per gram in subendocardial to subepicardial muscle) can be predicted from the DPTI: SPTI ratio of two pressure-time areas, where DPTI = the area between coronary and left ventric- ular pressures in diastole and SPTI = the area beneath the left ventricular systolic pressure.Early studies demonstrated subendocardial underperfusion when DPTI: SPTI was below 0.7, but more recent studies show that this critical ratio is about 0.4.Applying the results of these animal studies to man must be done very cautiously.Peak ventricular systolic pressure is better than SPTI in predicting myocardial oxygen needs, but neither measure allows for changes in wall tension or contractility.Second, increased coronary vascular resistance at maximal vasodilatation results in subendocardial underperfusion at t) PI'l: SPTI ratios above 0.4; these resistances increase with myocardial edema, hypertrophy, coronary vessel disease or in- creased blood viscosity.Finally, DPTI probably overestimates the actual mean pressure drop across the coronary vascular bed because in diastole intramyocardial tissue pressures may be 20-30 mm Hg.SUBENDOCARDIAL MUSCLE (the innermost or deepest quarter or one-third of the thickness of the free wall of the left or right ventricle) is exceptionally vulnerable to necrosis and fibrosis, both when coronary arteries are normal and when they are narrowed by atheroma.In patients with normal coronary arteries, left ventricular subendocardial damage has been noted when there is severe aortic stenosis or incompetence,' hemorrhagic shock,6 I pulmonary em- bolism,7 prolonged hypothermia,8 after cardiopulmonary bypass,9' 10 and in some types of cyanotic heart disease.Similar damage to right ventricular sub- endocardial muscle has also been found in patients with right ventricular hypertrophy, especially if they also have cyanotic heart disease.1 2, 11, 12 When coronary arteries are severely narrowed by atheroma, there may be infarction that is either entirely suben- docardial or that, even if transmural, shows more in-
Caveolins and the regulation of endothelial nitric oxide synthase in the heart
Authors: O FERON, J BALLIGAND
Journal: Cardiovascular Research (2006)

Virtually all cell types within the myocardium express caveolae, where cell-specific isoforms of caveolin both maintain the structural organisation of these cholesterol-rich of the plasmalemma and serve as scaffolds for the dynamic constitution of "signalosomes", or hubs concentrating numerous transmembrane signaling proteins and their effectors. Analysis of the phenotype of mice with genetic deletion or overexpression of specific caveolin isoforms has provided key evidence for the importance of caveolins and caveolae in several aspects of the cardiovascular biology, including vascular contractility, lipid metabolism, angiogenesis, or the control of cardiac hypertrophy. Among specific protein–protein interactions involving caveolins in cardiac tissue, these genetic models unequivocally confirmed the functional importance of the dynamic association of the endothelial isoform of nitric oxide synthase (eNOS) for its post-translational regulation in endothelial cells and cardiac myocytes, which bears on the enzyme's capacity to modulate nitric oxide (NO)-dependent endothelial function, angiogenesis, and excitation–contraction coupling. We will review the current understanding of this regulation of eNOS (and potentially other NOS isoforms) through protein–protein interactions involving several G-protein-coupled receptors and other allosteric modulators in the context of emerging paradigms on the regulation of cardiac function by NO.
Adherence with Twice-daily Dosing of Inhaled Steroids
Authors: ANDREA J. APTER, SUSAN T. REISINE, GLENN AFFLECK, ERIK BARROWS, RICHARD L. ZuWALLACK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Poor adherence to medication regimens may be contributing to the recent increase in asthma morbidity and mortality. We examined patient characteristics that may influence adherence to twice-daily inhaled steroid regimens. Fifty adults with moderate to severe asthma completed questionnaires examining sociodemographics, asthma severity, and health locus of control. Adherence was electronically monitored for 42 d. Following monitoring, patients' understanding of asthma pathophysiology and the function of inhaled corticosteroids were assessed. Patient beliefs about the effectiveness and convenience of these medications, and their perception of communications with their clinician were measured. Mean adherence was 63% ± 38%; 54% of subjects recorded at least 70% of the prescribed number of inhaled-steroid actuations. Factors associated with poor adherence were less than 12 yr of formal education (p < 0.001), poor patient–clinician communication (p < 0.001), household income less than $20,000 (p = 0.002), Spanish as primary language (p = 0.005), and minority status (p = 0.007). In a multiple logistic regression analysis, less than 12 yr of formal education (OR: 6.72; CI: 1.10 to 41.0) and poor patient–clinician communication (OR: 1.2; CI: 1.01 to 1.55) were independently associated with poor adherence. These results emphasize the importance of socioeconomic status and adequate patient–clinician communication for adherence to inhaled-steroid schedules.
Tenosynovitis with acute onset: unexpected giant cell tumour of the tendon sheath
Authors: E Kruithof
Journal: Annals of the Rheumatic Diseases (2002)

The “case study in diagnostic imaging”, reported by Peh et al illustrates nicely a giant cell tumour of the tendon sheath as a slowly progressing, mildly tender mass of the wrist.1 Here we report another case of giant cell tumour of the tendon sheath, which had an unusual disease onset.

A 33 year old man presented with acute swelling and severe pain of the palmar side of the right hand. He had symptoms of carpal …
Unequal sister chromatid exchange. A mechanism affecting Ig gene arrangement and expression.
Authors: S A Tilley, B K Birshtein
Journal: The Journal of Experimental Medicine (1985)

Two gamma 2a gene forms in the MPC11 mouse myeloma cell line (gamma 2b, K) have been localized to the expressed H chain chromosome, where they exist in tandem downstream of the expressed gamma 2b gene. The gamma 2a gene duplication has apparently occurred by spontaneous, unequal sister chromatid exchange (SCE) in a B lymphoid precursor of MPC11 or in MPC11 itself. It is especially significant that either of the tandem gamma 2a gene forms may be used in the class switch from gamma 2b to gamma 2a production occurring in the MPC11 line, indicating that heavy chain constant region (CH) gene duplication (or deletion) may be a mechanism normally impinging on CH gene expression. The gamma 2a genes of MPC11 undergo further copy number variation via unequal SCE in variants of this line derived by mutagenesis and selection for altered H chain production. The remarkable frequency with which copy number variation occurs in these cells suggests that unequal SCE may play a physiological role in CH gene arrangement and expression.
Regulation of alternative splicing by the circadian clock and food related cues
Authors: Nicholas J McGlincy, Amandine Valomon, Johanna E Chesham, Elizabeth S Maywood, Michael H Hastings, Jernej Ule
Journal: Genome biology (2012)

Abstract Background The circadian clock orchestrates daily rhythms in metabolism, physiology and behaviour that allow organisms to anticipate regular changes in their environment, increasing their adaptation. Such circadian phenotypes are underpinned by daily rhythms in gene expression. Little is known, however, about the contribution of post-transcriptional processes, particularly alternative splicing. Results Using Affymetrix mouse exon-arrays, we identified exons with circadian alternative splicing in the liver. Validated circadian exons were regulated in a tissue-dependent manner and were present in genes with circadian transcript abundance. Furthermore, an analysis of circadian mutant Vipr2 -/- mice revealed the existence of distinct physiological pathways controlling circadian alternative splicing and RNA binding protein expression, with contrasting dependence on Vipr2-mediated physiological signals. This view was corroborated by the analysis of the effect of fasting on circadian alternative splicing. Feeding is an important circadian stimulus, and we found that fasting both modulates hepatic circadian alternative splicing in an exon-dependent manner and changes the temporal relationship with transcript-level expression. Conclusions The circadian clock regulates alternative splicing in a manner that is both tissue-dependent and concurrent with circadian transcript abundance. This adds a novel temporal dimension to the regulation of mammalian alternative splicing. Moreover, our results demonstrate that circadian alternative splicing is regulated by the interaction between distinct physiological cues, and illustrates the capability of single genes to integrate circadian signals at different levels of regulation.
Comprehensive Surgical Management of Congenital Heart Disease
Authors: Marc R de Leval
Journal: Journal of the Royal Society of Medicine (2004)

Richard Jonas has performed the remarkable feat of writing, virtually single-handedly, a comprehensive textbook on congenital heart surgery very much based on his own practice. The book is divided into three sections. The first includes a chapter on basic surgical techniques, which is welcome and practical. The same applies to the chapter on biomaterials for congenital cardiac surgery. This section also includes a chapter on anaesthesia and intensive care written by two co-authors. Both are comprehensive and are supported by a very large clinical experience.

In section two, nearly 60 pages are devoted to cardiopulmonary bypass. This emphasis reflects the view of Jonas that cardiopulmonary bypass is a dominant determinant factor of surgical outcomes. It is also a reflection of the many and important contributions he has made in elucidating the physiopathology of extracorporeal perfusion and organ protection (the brain in particular). The third and main section describes the specific congenital cardiac anomalies in well structured chapters that highlight best current practice, preceded by anatomical and physiological descriptions and ending with a summary of current results from leading institutions. The book is very well written. The illustrations, by Rebekah Dodson, are outstanding. This book is a display of superior individual knowledge—virtually encyclopaedic. The most difficult technical procedures are described with accuracy, in simple terms that reflect the skills and talents of a masterful surgeon. Any congenital cardiac surgeon, any surgical trainee interested in congenital cardiac surgery, will consult this book with great pleasure.
Economic Opportunities and Challenges for Pharmacogenomics
Authors: Patricia A. Deverka, John Vernon, Howard L. McLeod
Journal: The Annual Review of Pharmacology and Toxicology (2010)

Economic evaluation provides health care decision makers with a powerful tool for resource allocation decisions because it offers a framework for comparing the costs and benefits of competing interventions or options. This paper reviews how economic analyses have been applied to the field of pharmacogenomics, both by the pharmaceutical industry to inform investment decisions and by payers to make coverage decisions. There is much anticipation that pharmacogenomic testing is likely to be cost-effective because it uses genomic information to improve drug effectiveness and reduce toxicity both in the drug development process and at the bedside. However, the demonstration of economic benefits first requires that pharmacogenomic testing show evidence of clinical effectiveness. This will only be achieved by greater participation of pharmacogenomics experts in comparative effectiveness research and additional emphasis on including costs in the determination of the relative value of pharmacogenomic testing to the health care system.
Inhibition of T-tropic HIV Strains by Selective Antagonization of the Chemokine Receptor CXCR4
Authors: Dominique Schols, Sofie Struyf, Jo Van Damme, José A. Esté, Geoffrey Henson, Erik De Clercq
Journal: The Journal of Experimental Medicine (1997)

Bicyclams are a novel class of antiviral compounds that are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2. Surprisingly, however, when the prototype compound AMD3100 was tested against M-tropic virus strains such as BaL, ADA, JR-CSF, and SF-162 in human peripheral blood mononuclear cells, the compound was completely inactive. Because of the specific and potent inhibitory effect of AMD3100 on T-tropic viruses, but not M-tropic viruses, it was verified that AMD3100 interacts with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-tropic viruses. AMD3100 dose dependently inhibited the binding of a specific CXCR4 monoclonal antibody to SUP-T1 cells as measured by flow cytometry. It did not inhibit the binding of the biotinylated CC-chemokine macrophage inflammatory protein (MIP) 1α or MIP-1β, ligands for the chemokine receptor CCR5 (the main coreceptor for M-tropic viruses). In addition, AMD3100 completely blocked (a) the Ca2+ flux at 100 ng/ml in lymphocytic SUP-T1 and monocytic THP-1 cells, and (b) the chemotactic responses of THP-1 cells induced by stromal cell–derived factor 1α, the natural ligand for CXCR4. Finally, AMD3100 had no effect on the Ca2+ flux induced by the CC-chemokines MIP-1α, regulated on activation normal T cell expressed and secreted (RANTES; also a ligand for CCR5), or monocyte chemoattractant protein 3 (a ligand for CCR1 and CCR2b), nor was it able to induce Ca2+ fluxes by itself. The bicyclams are, to our knowledge, the first low molecular weight anti-HIV agents shown to act as potent and selective CXCR4 antagonists.
Low cognitive ability in early adulthood is associated with reduced lung function in middle age: the Vietnam Experience Study
Authors: D. Carroll, G. D. Batty, L. H. Mortensen, I. J. Deary, A. C. Phillips
Journal: Thorax (2011)

<h3>Objective</h3> Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age. <h3>Methods</h3> Participants were 4256 male Vietnam-era US veterans. Cognitive ability was assessed by the Army General Technical Test on enlistment when participants were, on average, 20 years old (range: 17–34). Data on ethnicity and place of service were extracted from army files. Smoking behaviour, alcohol consumption, basic socio-demographics and whether participants had a physician-diagnosed chronic disease were determined by telephonic interview in middle age in 1985. Forced expiratory volume in one second (FEV<sub>1</sub>) was measured by spirometry at a 3-day medical examination in 1986. Height and weight were also measured. <h3>Results</h3> In linear regression models, poor cognitive ability in early adulthood was associated with reduced lung function in middle age, first adjusting for age and height, β=0.17, p&lt;0.001, then additionally adjusting for circumstantial, socio-demographic, lifestyle and health factors, β=0.12, p=0.001. The same results were obtained when the analysis was confined to non-smokers. <h3>Conclusion</h3> Not only is lung function related to subsequent cognitive ability, but poor cognitive ability earlier in life is also associated with reduced lung function in middle age.