tbuckley/cabot-search huggingface dataset:
Mid-year review: physical inactivity universally accepted as the biggest public health problem of the 21st century, shoulder exam challenges, and progress against the scourges of anterior knee pain and ACL injuries
Authors: K M Khan
Journal: British Journal of Sports Medicine (2009)

As the northern hemisphere embarks on various degrees of summer stupor, and the southern hemisphere weathers the winter with a crowd of football codes, I take this chance to alert you to what many have considered highlights of the year to date.

Professor Steven Blair opened BJSM’s year by announcing a “surge” against physical inactivity.1 Interestingly there has been no push-back against Professor Blair’s powerful argument and compelling data. How time flies when I consider that Dr Frank Booth’s classic declaration of war against physical inactivity was in 2000—almost a decade ago!2

Now is the time to redouble our efforts to promote physical activity as the single most useful health modality. We also need to be cohesive so that lawmakers are not confused by multiple messages or by competing interests. To this end, BJSM fully endorses the …
Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning
Authors: Frédéric Baron, Jennifer E. Baker, Rainer Storb, Theodore A. Gooley, Brenda M. Sandmaier, Michael B. Maris, David G. Maloney, Shelly Heimfeld, Dmitrij Oparin, Eustacia Zellmer, Jerald P. Radich, F. Carl Grumet, Karl G. Blume, Thomas R. Chauncey, Marie-Térèse Little
Journal: Blood (2004)
BEAMing Sheds Light on Drug Resistance
Authors: Josh Lauring, Ben Ho Park
Journal: Clinical Cancer Research (2011)

Targeted therapies against somatically altered genes are currently used for the treatment of many human cancers. The nascent technology known as BEAMing has the potential to increase the clinical utility of these agents because it allows for the detection of cancer mutations in peripheral blood, providing a rapid assessment of tumor mutation status.
Inhibition of Src Phosphorylation Alters Metastatic Potential of Osteosarcoma <i>In vitro</i> but not <i>In vivo</i>
Authors: Pooja Hingorani, Wendong Zhang, Richard Gorlick, E. Anders Kolb
Journal: Clinical Cancer Research (2009)

Pulmonary metastasis remains the major cause of mortality in osteosarcoma. Src tyrosine kinase is a key player involved in metastatic pathways in multiple human cancers. c-Src has been shown to be expressed and phosphorylated in osteosarcoma cell lines and inhibiting Src phosphorylation in these cells causes inhibition of the metastatic phenotype in vitro. We studied the effect of inhibition of Src phosphorylation in preventing the growth and development of pulmonary metastases in osteosarcoma.Dasatinib, a dual Src-Abl kinase inhibitor, was used to study the effect of Src kinase inhibition on proliferation, adhesion, and invasion of osteosarcoma cell lines in vitro and in preventing the development of pulmonary metastases in a spontaneously metastatic mouse model.In vitro, phosphorylation of Src and its downstream signaling molecules such as focal adhesion kinase, Crk-associated substrate, and c-Jun was inhibited at nanomolar concentrations of dasatinib. Dasatinib was not cytotoxic against the osteosarcoma cells with the IC(50) ranging from 10 to 20 micromol/L but effectively inhibited the adhesion and migration of osteosarcoma cells at 10 to 100 nmol/L. However, in vivo, dasatinib did not inhibit the development of pulmonary metastases despite complete inhibition of Src phosphorylation in the primary tumors. No effect was seen in the primary tumor growth and the degree of apoptosis.These results suggest that Src kinase activation might not be the primary pathway involved in the development of pulmonary metastases in osteosarcoma.
Peptide‐Directed Spatial Organization of Biomolecules in Dynamic Gradient Scaffolds
Authors: Lesley W. Chow, Astrid Armgarth, Jean‐Philippe St‐Pierre, Sergio Bertazzo, Cristina Gentilini, Claudia Aurisicchio, Seth D. McCullen, Joseph A. M. Steele, Molly M. Stevens
Journal: Advanced Healthcare Materials (2014)

Specific binding peptides are used to spatially organize biomolecule gradients within an electrospun fiber scaffold. Different biomolecule-binding peptide–polymer conjugates are sequentially co-electrospun with a fiber-forming host polymer to generate opposing gradients of peptide functionalization. The binding peptides specifically and non-covalently guide the spatial arrangement of biomolecules into dynamic gradients within the scaffold, mimicking biological gradients found in native tissues. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effects of anti-Ia sera on mitogenic responses. II. Differential expression of the Ia marker on phytohemagglutinin and concanavalin A-reactive T cells.
Authors: J E Niederhuber, J A Frelinger, M S Dine, P Shoffner, E Dugan, D C Shreffler
Journal: The Journal of Experimental Medicine (1976)

Genes mapping in the I region of the H-2 complex control a system of lymphocyte alloantigens (Ia) which are expressed on a subpopulation of T cells and on most B cells. Specific anti-Ia serum in the presence of rabbit complement removed the splenic T-cell subpopulation responsive to Con-A, but did not affect the response to phytohemagglutinin (PHA) or Leucoagglutinin. Antibodies specific for Ia, H-2K, or H-2D membrane antigens were used without complement to pretreat spleen cells. These antibody pretreated cells responded normally to Con-A and PHA.
Differential Regulation of Estrogen Receptor α Turnover and Transactivation by Mdm2 and Stress-Inducing Agents
Authors: Vanessa Duong, Nathalie Boulle, Sylvain Daujat, Jérôme Chauvet, Sandrine Bonnet, Henry Neel, Vincent Cavaillès
Journal: Cancer Research (2007)

Abstract In mammalian cells, the level of estrogen receptor α (ERα) is rapidly decreased upon estrogen treatment, and this regulation involves proteasome degradation. Using different approaches, we showed that the Mdm2 oncogenic ubiquitin-ligase directly interacts with ERα in a ternary complex with p53 and is involved in the regulation of ERα turnover (both in the absence or presence of estrogens). Several lines of evidence indicated that this effect of Mdm2 required its ubiquitin-ligase activity and involved the ubiquitin/proteasome pathway. Moreover, in MCF-7 human breast cancer cells, various p53-inducing agents (such as UV irradiation) or treatment with RITA (which inhibits the interaction of p53 with Mdm2) stabilized ERα and abolished its 17β-estradiol–dependent turnover. Interestingly, our data indicated that ligand-dependent receptor turnover was not required for efficient transactivation. Altogether, our results indicate that the Mdm2 oncoprotein and stress-inducing agents complexly and differentially regulate ERα stability and transcriptional activity in human cancer cells. [Cancer Res 2007;67(11):5513–21]
Diminished Glucose Tolerance and Immunoreactive Insulin Response in Patients with Nonischemic Cardiac Disease
Authors: PHILIP O. ETTINGER, HENRY A. OLDEWURTEL, ALLEN B. WEISSE, TIMOTHY J. REGAN, Marilyn A. Weber
Journal: Circulation (1968)

Intravenous infusion of glucose in patients with compensated nonischemic cardiovascular disease has demonstrated that the glucose disappearance slope, G K , is significantly lower than in normal subjects. Immunoassay of plasma insulin in 13 of these cardiac patients showed a reduced insulin response to hyperglycemia in the majority. All had a delayed decline of plasma insulin values. Plasma free fatty acids (FFA) were significantly elevated in the fasting state but were not significantly correlated with the reduced G K . During the acute hyperglycemia, plasma free fatty acid, potassium, and inorganic phosphate concentrations declined as in the normal subjects. Although cardiac index was reduced in most patients, a linear correlation with G K was not obtained. To examine the possible role of enhanced sympathetic stimulation seen in cardiac patients, norepinephrine was infused into normal subjects during a glucose-tolerance test (GTT). A decline in glucose tolerance and plasma insulin was observed to levels approximating those seen in the cardiac patients, suggesting a neurohumoral mechanism for the glucose intolerance in cardiac patients. It would therefore appear that the glucose intolerance in compensated cardiac subjects with a reduced cardiac output is frequently an acquired rather than a genetically determined metabolic disorder.
QUINSY AND RETROPHARYNGEAL ABSCESS
Authors: R. S. Stevenson
Journal: BMJ (1938)

The term " quinsy " had in the past a much less restricted application than it has to-day.To mediaeval surgeons cynanche meant any kind of a sore throat-including what appears to have been diphtheria-and even Morell Mackenzie (1880) used quinsy as a synonym for acute tonsillitis.To-day, however, we take it that a quinsy is a peritonsillar abscess-suppuration in the tissues of the soft palate outside the capsule of the tonsil.It does not originate in these tissues, but results from infection of the crypts of the intratonsillar fossa.The fossa, which is often inaccurately named, is confused with the supra- tonsillar fossa or sinus, above the tonsil and between the pillars of the fauces; it has been called by some author- ities the tonsillar recess, superior tonsillar fossa, or crypta magna, and is situLated in the upper pole of the tonsil, going right down to the capsule (see Fig. 1).It becomes
Fate of biomedical research protocols and publication bias in France: retrospective cohort study
Authors: Evelyne Decullier, Véronique Lhéritier, François Chapuis
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level. <b>Design</b> Retrospective cohort study. <b>Setting</b> Representative sample of 25/48 French research ethics committees in 1994. <b>Protocols</b> 649 research protocols approved by committees, with follow-up information. <b>Main outcome measures</b> Protocols9 initial characteristics (design, study size, investigator) abstracted from committees9 archives; follow-up information (rates of initiation, completion, and publication) obtained from mailed questionnaire to principal investigators. <b>Results</b> Completed questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%) studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were published. Studies with confirmatory results were more likely to be published as scientific papers than were studies with inconclusive results (adjusted odds ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with confirmatory results were published more quickly than studies with inconclusive results (hazard ratio 2.48, 1.36 to 4.55). <b>Conclusion</b> At a national level, too many research studies are not completed, and among those completed too many are not published. We suggest capitalising on research ethics committees to register and follow all authorised research on human participants on a systematic and prospective basis.
A Double‐Antibody Assay for Grass Pollen‐Specific IgG in Human Serum
Authors: P. Prahl, P. Skov, H. Løwenstein, A. Hjorter, U. Minuva, E. Nexø, S. Norn, P. Stahl Skov, B. Weeke, O. ØSterballe
Journal: Allergy (1981)

A double‐antibody radioimmunoassay for measurement of grass pollen antigen‐specific IgG in serum is described. Grass pollen antigens were used to show a correlation between the results obtained by this method and those obtained by measuring blocking antibodies by inhibition of antigen‐induced leukocyte histamine release. The new technique described is convenient, sensitive, specific and reproducible and can be recommended for clinical use.
Rapamycin Inhibits Ezrin-Mediated Metastatic Behavior in a Murine Model of Osteosarcoma
Authors: Xiaolin Wan, Arnulfo Mendoza, Chand Khanna, Lee J. Helman
Journal: Cancer Research (2005)

Abstract Osteosarcoma is the most frequent primary malignant tumor of bone with a high propensity for metastasis. We have previously showed that ezrin expression is necessary for metastatic behavior in a murine model of osteosarcoma (K7M2). In this study, we found that a mechanism of ezrin-related metastatic behavior is linked to an Akt-dependent mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (S6K1)/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) pathway. Suppression of ezrin expression either by antisense transfection or by small interfering RNAs or disruption of ezrin function by transfection of a dominant-negative ezrin-T567A mutant led to decreased expression and decreased phosphorylation of both S6K1 and 4E-BP1. Proteosomal inhibition by MG132 reversed antisense-mediated decrease of S6K1 and 4E-BP1 protein expression, but failed to affect the effect of ezrin on phosphorylation of S6K1 and 4E-BP1. Blockade of the mTOR pathway with rapamycin or its analog, cell cycle inhibitor-779 led to significant inhibition of experimental lung metastasis in vivo. These results suggest that blocking the mTOR/S6K1/4E-BP1 pathway may be an appropriate target for strategies to reduce tumor cell metastasis.
Validation of Nasal Pressure for the Identification of Apneas/Hypopneas during Sleep
Authors: Steven J. Heitman, Raj S. Atkar, Eric A. Hajduk, Richard A. Wanner, W. Ward Flemons
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The reference standard for identifying apneas and hypopneas is a pneumotachograph, but using this can disrupt sleep. Nasal airflow estimation by measuring nasal pressure via nasal prongs is better tolerated by patients. However, nasal pressure has not been validated, using an event-by-event analysis, for detecting apneas/hypopneas during sleep. Eleven patients undergoing polysomnography wore a nasal mask capable of measuring nasal airflow (via pneumotachograph) and nasal pressure simultaneously. Each study was screened for respiratory disturbances, and from these 550 were randomly selected and blindly scored as an apnea/hypopnea or no event each using the pneumotachograph, nasal pressure, square root nasal pressure, and respiratory inductance sum signals independently. Agreement was measured using Cohen's kappa statistic. Intermeasurement agreements between the pneumotachograph and nasal pressure, square root nasal pressure, and respiratory inductance plethysmography sum were 0.76, 0.73, and 0.50, respectively. Inter- and intrarater agreements were, respectively, 0.68 and 0.60 for the pneumotachograph, 0.66 and 0.82 for nasal pressure, 0.61 and 0.78 for square root nasal pressure, and 0.47 and 0.76 for respiratory inductance plethysmography sum. These results indicate that nasal pressure has excellent agreement compared with a pneumotachograph and very good inter-/intrarater agreement. Square root transformation of the nasal pressure signal does not improve these levels of agreement, indicating that it is unnecessary in routine clinical practice for scoring apneas/hypopneas.
A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing
Authors: Stephen E. Kimmel, Benjamin French, Scott E. Kasner, Julie A. Johnson, Jeffrey L. Anderson, Brian F. Gage, Yves D. Rosenberg, Charles S. Eby, Rosemary A. Madigan, Robert B. McBane, Sherif Z. Abdel-Rahman, Scott M. Stevens, Steven Yale, Emile R. Mohler, Margaret C. Fang, Vinay Shah, Richard B. Horenstein, Nita A. Limdi, James A.S. Muldowney, Jaspal Gujral, Patrice Delafontaine, Robert J. Desnick, Thomas L. Ortel, Henny H. Billett, Robert C. Pendleton, Nancy L. Geller, Jonathan L. Halperin, Samuel Z. Goldhaber, Michael D. Caldwell, Robert M. Califf, Jonas H. Ellenberg
Journal: New England Journal of Medicine (2013)

The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.
“Selfish Spermatogonial Selection”: A Novel Mechanism for the Association Between Advanced Paternal Age and Neurodevelopmental Disorders
Authors: Anne Goriely, John J. McGrath, Christina M. Hultman, Andrew O.M. Wilkie, Dolores Malaspina
Journal: American Journal of Psychiatry (2013)

There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. The authors present a novel mechanism that may contribute to this association. Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare disorders related to paternal age (e.g., Apert syndrome, achondroplasia), this process is known as "selfish spermatogonial selection." This mechanism favors propagation of germ cells carrying pathogenic mutations, increasingly skews the mutational profile of sperm as men age, and enriches de novo mutations in the offspring of older fathers that preferentially affect specific cellular signaling pathways. This mechanism not only offers a parsimonious explanation for the association between advanced paternal age and various neurodevelopmental disorders but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle), and some epidemiological features of these disorders. The authors outline hypotheses to test this model. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications.
The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases
Authors: Beckley K. Davis, Haitao Wen, Jenny P.-Y. Ting
Journal: Annual Review of Immunology (2011)

Inflammasome activation leads to caspase-1 activation, which causes the maturation and secretion of pro-IL-1β and pro-IL-18 among other substrates. A subgroup of the NLR (nucleotide-binding domain, leucine-rich repeat containing) proteins are key mediators of the inflammasome. Studies of gene-deficient mice and cells have implicated NLR inflammasomes in a host of responses to a wide range of microbial pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. Determining exactly how the inflammasome is activated in these diseases and disease models remains a challenge. This review presents and integrates recent progress in the field.
Muscle Dysfunction in Patients with Lung Diseases. A Growing Epidemic
Authors: Esther Barreiro, Jacob I. Sznajder, Gustavo A. Nader, G. R. Scott Budinger
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The lung is tasked with the provision of oxygen to fuel oxidative phosphorylation and with the removal of its byproduct carbon dioxide and is therefore a key player in organismal metabolism. When viewed from this perspective, it is unsurprising that lung dysfunction is associated with suboptimal function of other metabolic organs, most notably of skeletal muscle. A prevalent example is observed in patients with chronic obstructive pulmonary disease (COPD), which is a leading cause of death worldwide and one of the few major diseases for which mortality continues to climb (1). Skeletal muscle dysfunction, defined as the loss of either muscle strength or endurance, is a prominent comorbidity in patients with COPD that impairs their exercise capacity, quality of life, and disease prognosis (2–8). For example, quadriceps muscle dysfunction, which is primarily characterized by reduced muscle force generation, is observed in one-third of all patients with COPD even at very early stages of their disease, where it is associated with decreased exercise tolerance, a reduced quality of life, and increased mortality (2–8). In patients with COPD, other comorbidities, including muscle wasting, malnutrition, chronic heart failure, exacerbations, and reduced physical activity, can further impair muscle function (4, 7). Sarcopenia, the age-associated loss of skeletal muscle mass and function, is present in as many as 10% of older hospitalized adults (9, 10). Although limb muscle dysfunction is often the most clinically evident problem in patients with COPD, respiratory muscle dysfunction is also present and may contribute to the development and persistence of hypoventilatory respiratory failure in these patients (11, 12). Combined, the presence of respiratory and peripheral muscle dysfunction and underlying sarcopenia results in prolonged hospitalizations and reduced rates of physical activity, creating a vicious circle of progressive muscle dysfunction and morbidity.
Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection
Authors: J.W. Pape, S.S. Jean, J.L. Ho, A. Hafner, W.D. Johnson
Journal: The Lancet (1993)

SummaryTuberculosis occurring with human immunodeficiency virus (HIV) infection is a serious and growing public health problem. We have carried out a randomised clinical trial of a 12-month course of isoniazid plus vitamin B6 versus vitamin B6 alone in Port-au-Prince, Haiti, to assess the efficacy of isoniazid in preventing active tuberculosis in symptom-free HIV-infected individuals. The effect of prophylaxis on the development of HIV disease, AIDS, and death was also investigated.118 subjects were assigned treatment with isoniazid plus B6 (n=58) or B6 alone (n=60) between 1986 and 1989. The treatment groups were similar at study entry in demographic, clinical, and immunological characteristics. Interim analysis in 1990 revealed no significant difference in tuberculosis outcome measures. Follow-up was continued until 1992, at which time significant protection by isoniazid against the development of tuberculosis was apparent, both for the whole study population and for subjects positive for purified protein derivative of tuberculin (PPD). The incidence of tuberculosis was lower in isoniazid recipients than in patients who received B6 alone (2·2 vs 7·5 per 100 person-years). The relative risk of tuberculosis was 3·4 (95% CI 1·1-10·6) for B6 alone versus isoniazid plus B6 (p<0·05). Isoniazid also delayed progression to HIV disease and AIDS and death. Thus isoniazid effectively decreases the incidence of tuberculosis and delays the onset of HIV-related disease in symptom-free HIV-seropositive individuals. Isoniazid prophylaxis should be considered for HIV-seropositive, PPD-positive subjects, and may also be appropriate for PPD-negative patients in areas where tuberculosis is highly endemic.