tbuckley/cabot-search huggingface dataset:
Glycated haemoglobin A1c for diagnosing diabetes in Chinese population: cross sectional epidemiological survey
Authors: Y. Bao, X. Ma, H. Li, M. Zhou, C. Hu, H. Wu, J. Tang, X. Hou, K. Xiang, W. Jia
Journal: BMJ (2010)

<b>Objectives</b> To evaluate haemoglobin A1c (HbA<sub>1c</sub>) in diagnosing diabetes and identify the optimal HbA<sub>1c</sub> threshold to be used in Chinese adults. <b>Design</b> Multistage stratified cross sectional epidemiological survey. <b>Setting</b> Shanghai, China, 2007-8. <b>Participants</b> 4886 Chinese adults over 20 years of age with no history of diabetes. <b>Main outcome measures</b> Performance of HbA<sub>1c</sub> at increasing thresholds for diagnosing diabetes. <b>Results</b> The area under the receiver operating characteristics curve for detecting undiagnosed diabetes was 0.856 (95% confidence interval 0.828 to 0.883) for HbA<sub>1c</sub> alone and 0.920 (0.900 to 0.941) for fasting plasma glucose alone. Very high specificity (96.1%, 95% confidence interval 95.5% to 96.7%) was achieved at an HbA<sub>1c</sub> threshold of 6.3% (2 SD above the normal mean). Moreover, the corresponding sensitivity was 62.8% (57.1% to 68.3%), which was equivalent to that of a fasting plasma glucose threshold of 7.0 mmol/l (57.5%, 51.7% to 63.1%) in detecting undiagnosed diabetes. In participants at high risk of diabetes, the HbA<sub>1c</sub> threshold of 6.3% showed significantly higher sensitivity (66.9%, 61.0% to 72.5%) than both fasting plasma glucose ≥7.0 mmol/l (54.4%, 48.3% to 60.4%) and HbA<sub>1c</sub> ≥6.5% (53.7%, 47.6% to 59.7%) (P&lt;0.01). <b>Conclusions</b> An HbA<sub>1c</sub> threshold of 6.3% was highly specific for detecting undiagnosed diabetes in Chinese adults and had sensitivity similar to that of using a fasting plasma glucose threshold of 7.0 mmol/l. This optimal HbA<sub>1c</sub> threshold may be suitable as a diagnostic criterion for diabetes in Chinese adults when fasting plasma glucose and oral glucose tolerance tests are not available.
Pharmacokinetics of Dactinomycin in a Pediatric Patient Population: a United Kingdom Children's Cancer Study Group Study
Authors: Gareth J. Veal, Michael Cole, Julie Errington, Annie Parry, Juliet Hale, Andrew D.J. Pearson, Karen Howe, Julia C. Chisholm, Carol Beane, Bernadette Brennan, Fiona Waters, Adam Glaser, Sue Hemsworth, Heather McDowell, Yvonne Wright, Kathy Pritchard-Jones, Ross Pinkerton, Gail Jenner, James Nicholson, Ann M. Elsworth, Alan V. Boddy
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Dactinomycin (actinomycin D) is an antitumor antibiotic used routinely to treat certain pediatric and adult cancers. Despite concerns over the incidence of toxicity, little is known about the pharmacology of dactinomycin. A study was done to investigate dactinomycin pharmacokinetics in children. Experimental Design: Dactinomycin was administered to 31 patients by bolus i.v. infusion, at doses of 0.70 to 1.50 mg/m2. Plasma concentrations were determined by liquid chromatography-mass spectrometry up to 24 hours after drug administration and National Cancer Institute Common Toxicity Criteria was assessed. Results: Pharmacokinetic data analysis suggested that a three-compartment model most accurately reflected dactinomycin pharmacokinetics. However, there was insufficient data available to fully characterize this model. A median peak plasma concentration (Cmax) of 25.1 ng/mL (range, 3.2-99.2 ng/mL) was observed at 15 minutes after administration. The median exposure (AUC0-6), determined in 16 patients with sampling to 6 hours, was 2.67 mg/L.min (range, 1.12-4.90 mg/L.min). After adjusting for body size, AUC0-6 and Cmax were positively related to dose (P = 0.03 and P = 0.04, respectively). Patients who experienced any level of Common Toxicity Criteria grade had a 1.46-fold higher AUC0-6, 95% confidence interval (1.02-2.09). AUC0-6 was higher in patients &amp;lt;40 kg, possibly indicating a greater toxicity risk. Conclusions: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped.
Therapeutic Effect of Anti–TNF-α Antibodies in an Experimental Model of Anti-Neutrophil Cytoplasm Antibody–Associated Systemic Vasculitis
Authors: Mark A Little, Gurjeet Bhangal, C Lucy Smyth, Marian T Nakada, H Terence Cook, Sussan Nourshargh, Charles D Pusey
Journal: Journal of the American Society of Nephrology (2005)

<h3>Background</h3> Change of direction and kicking have been described as the main actions resulting in adductor longus injury. Video descriptions of inciting events are lacking. <h3>Objective</h3> Perform a standardised visual video analysis of a series of acute adductor longus injuries in football. <h3>Study design</h3> Cross-sectional. <h3>Methods</h3> Video footage was reviewed by players, and assessed independently by five sports medicine professionals. Inciting events were described and categorised using standardised scoring, including playing situation, player/opponent behaviour, movement and body positions. <h3>Results</h3> Videos of acute adductor longus injuries in 17 professional male football players were analysed. Most injuries occurred in non-contact situations (71%), following a quick reaction to a change in play (53%). Injury actions were: change of direction (35%), kicking (29%), reaching (24%) and jumping (12%). Change of direction and reaching injuries were categorised as closed chain movements (59%), characterised by hip extension and abduction with external rotation. Kicking and jumping injuries were categorised as open chain (41%), characterised by a change from hip extension to hip flexion, and hip abduction to adduction, with external rotation. <h3>Conclusion</h3> Acute adductor longus injuries in football occur in a variety of situations. Player actions can be categorised into closed (change of direction and reaching) and open (kicking and jumping) chain movements involving triplanar hip motion. A rapid muscle activation during a rapid muscle lengthening appears to be the fundamental injury mechanism for acute adductor longus injuries.
Error-Prone Candidates Vie for Somatic Mutation
Authors: Vladimir Poltoratsky, Myron F. Goodman, Matthew D. Scharff
Journal: The Journal of Experimental Medicine (2000)

Antibodies play a major role in the resistance of higher organisms to disease. This is made possible because mice, humans, and other species have evolved three unusual molecular mechanisms that allow the generation of an enormously diverse repertoire of antibodies from a relatively small amount of genetic material. First, each antibody-forming B cell assembles different combinations of variable (V), diversity (D), and joining (J) minigenes to create an antibody with a unique antigen-binding site. Second, to generate the high-affinity antibodies that are required for survival, B cells target many point mutations to the V(D)J regions of the H and VJ region of the L chain immunoglobulin (Ig) genes. Those B cells that are making higher affinity antibodies are selected for further growth and differentiation, resulting in the affinity maturation of the antibody response. Third, B cells rearrange the H chain V region to various downstream C regions that encode the different isotypes. This makes it possible for each of the many antigen-binding sites to mediate the effector functions that are encoded in the different C region genes and to be distributed throughout the body 1.
Pronephric Tubulogenesis Requires Daam1-Mediated Planar Cell Polarity Signaling
Authors: Rachel K. Miller, Sol Gomez de la Torre Canny, Chuan-Wei Jang, Kyucheol Cho, Hong Ji, Daniel S. Wagner, Elizabeth A. Jones, Raymond Habas, Pierre D. McCrea
Journal: Journal of the American Society of Nephrology (2011)

Canonical β-catenin-mediated Wnt signaling is essential for the induction of nephron development. Noncanonical Wnt/planar cell polarity (PCP) pathways contribute to processes such as cell polarization and cytoskeletal modulation in several tissues. Although PCP components likely establish the plane of polarization in kidney tubulogenesis, whether PCP effectors directly modulate the actin cytoskeleton in tubulogenesis is unknown. Here, we investigated the roles of Wnt PCP components in cytoskeletal assembly during kidney tubule morphogenesis in Xenopus laevis and zebrafish. We found that during tubulogenesis, the developing pronephric anlagen expresses Daam1 and its interacting Rho-GEF (WGEF), which compose one PCP/noncanonical Wnt pathway branch. Knockdown of Daam1 resulted in reduced expression of late pronephric epithelial markers with no apparent effect upon early markers of patterning and determination. Inhibiting various points in the Daam1 signaling pathway significantly reduced pronephric tubulogenesis. These data indicate that pronephric tubulogenesis requires the Daam1/WGEF/Rho PCP pathway.
Gene expression profiling gets to the root of human hair follicle stem cells
Authors: George Cotsarelis
Journal: Journal of Clinical Investigation (2005)

Hair follicle stem cells sustain growth and cycling of the hair follicle and are located in the permanent portion of the follicle known as the bulge. In this issue of the JCI, Ohyama et al. report the characterization of global gene expression patterns of human hair follicle stem cells after their isolation using sophisticated laser capture techniques to microdissect out bulge cells. They discovered a panel of cell surface markers useful for isolating living hair follicle stem cells, a finding with potential therapeutic implications since isolated stem cells in mice can generate new hair follicles when transplanted to other mice. The findings of Ohyama et al. validate the use of the mouse for studying hair follicle biology but also underscore critical differences between mouse and human stem cell markers. In particular, CD34, which delineates hair follicle stem cells in the mouse, is not expressed by human hair follicle stem cells, while CD200 is expressed by stem cells in both species. Ultimately, this information will assist efforts to develop cell-based and cell-targeted treatments for skin disease.
Early recurrence in standard-risk medulloblastoma patients with the common idic(17)(p11.2) rearrangement
Authors: G. A. Bien-Willner, D. Lopez-Terrada, M. B. Bhattacharjee, K. U. Patel, P. Stankiewicz, J. R. Lupski, J. D. Pfeifer, A. Perry
Journal: Neuro-Oncology (2012)

Medulloblastoma is diagnosed histologically; treatment depends on staging and age of onset. Whereas clinical factors identify a standard- and a high-risk population, these findings cannot differentiate which standard-risk patients will relapse and die. Outcome is thought to be influenced by tumor subtype and molecular alterations. Poor prognosis has been associated with isochromosome (i)17q in some but not all studies. In most instances, molecular investigations document that i17q is not a true isochromosome but rather an isodicentric chromosome, idic(17)(p11.2), with rearrangement breakpoints mapping within the REPA/REPB region on 17p11.2. This study explores the clinical utility of testing for idic(17)(p11.2) rearrangements using an assay based on fluorescent in situ hybridization (FISH). This test was applied to 58 consecutive standard- and high-risk medulloblastomas with a 5-year minimum of clinical follow-up. The presence of i17q (ie, including cases not involving the common breakpoint), idic(17)(p11.2), and histologic subtype was correlated with clinical outcome. Overall survival (OS) and disease-free survival (DFS) were consistent with literature reports. Fourteen patients (25%) had i17q, with 10 (18%) involving the common isodicentric rearrangement. The presence of i17q was associated with a poor prognosis. OS and DFS were poor in all cases with anaplasia (4), unresectable disease (7), and metastases at presentation (10); however, patients with standard-risk tumors fared better. Of these 44 cases, tumors with idic(17)(p11.2) were associated with significantly worse patient outcomes and shorter mean DFS. FISH detection of idic(17)(p11.2) may be useful for risk stratification in standard-risk patients. The presence of this abnormal chromosome is associated with early recurrence of medulloblastoma.
The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis
Authors: Hui Ling, Karen Pickard, Cristina Ivan, Claudio Isella, Mariko Ikuo, Richard Mitter, Riccardo Spizzo, Marc D Bullock, Cornelia Braicu, Valentina Pileczki, Kimberly Vincent, Martin Pichler, Verena Stiegelbauer, Gerald Hoefler, Maria I Almeida, Annie Hsiao, Xinna Zhang, John N Primrose, Graham K Packham, Kevin Liu, Krishna Bojja, Roberta Gafà, Lianchun Xiao, Simona Rossi, Jian H Song, Ivan Vannini, Francesca Fanini, Scott Kopetz, Patrick Zweidler-McKay, Xuemei Wang, Calin Ionescu, Alexandru Irimie, Muller Fabbri, Giovanni Lanza, Stanley R Hamilton, Ioana Berindan-Neagoe, Enzo Medico, Alex H Mirnezami, George A Calin, Milena S Nicoloso
Journal: Gut (2015)

<h3>Objective</h3> MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. <h3>Design</h3> We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atlas (TCGA) consortium and correlated with miR-224 status. We used the Kaplan–Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. <h3>Results</h3> MiR-224 expression increases consistently with tumour burden and microsatellite stable status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target and observed negative correlation (Spearman Rs=−0.44, p&lt;0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037, respectively), and shorter metastasis-free survival (HR 6.51, 95% CI 1.97 to 21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (HR 4.12, 95% CI 1.1 to 15.41, p=0.0175). <h3>Conclusions</h3> MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for survival of patients with CRC.
Effect of Dietary Protein Content on Weight Gain, Energy Expenditure, and Body Composition During Overeating
Authors: George A. Bray, Steven R. Smith, Lilian de Jonge, Hui Xie, Jennifer Rood, Corby K. Martin, Marlene Most, Courtney Brock, Susan Mancuso, Leanne M. Redman
Journal: JAMA (2012)

jor public health concern with more than 60% of adults in the United States categorized as overweight and more than 30% as obese. 1,2People who become obese have been in a positive energy balance for an extended period.Swinburn et al 3 have argued that this reflects an increase in food intake, but Church et al 4 have presented data showing that reduced occupational activity might account for the positive energy balance.Although a majority of people in the United States are overweight or obese, there is a significant number of people with normal weights who do not become overweight or obese.As obesity develops, a number of metabolic changes occur, which may not completely reverse when weight is lost. 5These differences may reflect differences in the way individuals handle the food they eat each day both during weight gain and weight loss.
Natural Image Statistics and Neural Representation
Authors: Eero P Simoncelli, Bruno A Olshausen
Journal: Annual Review of Neuroscience (2001)

▪ Abstract It has long been assumed that sensory neurons are adapted, through both evolutionary and developmental processes, to the statistical properties of the signals to which they are exposed. Attneave (1954) , Barlow (1961) proposed that information theory could provide a link between environmental statistics and neural responses through the concept of coding efficiency. Recent developments in statistical modeling, along with powerful computational tools, have enabled researchers to study more sophisticated statistical models for visual images, to validate these models empirically against large sets of data, and to begin experimentally testing the efficient coding hypothesis for both individual neurons and populations of neurons.
Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells.
Authors: N Inoue, K Hirata, M Yamada, Y Hamamori, Y Matsuda, H Akita, M Yokoyama
Journal: Circulation Research (1992)

Vascular endothelium, which produces endothelium-derived relaxing and constricting factors, plays an important role in regulating the vascular tone. We recently demonstrated that oxidized low density lipoprotein inhibited endothelium-dependent relaxation and that lysophosphatidylcholine accumulated during the oxidative modification of low density lipoprotein was the essential substance for the inhibition of endothelium-dependent relaxation. To clarify the mechanisms of the inhibitory effect of lysophosphatidylcholine, we used a bioassay system to investigate the effect of lysophosphatidylcholine on the production and/or release of endothelium-derived relaxing factor and its effect on the cytosolic Ca2+ level ([Ca2+]i) and phosphoinositide hydrolysis in cultured bovine aortic endothelial cells. [Ca2+]i was monitored by the fura 2 method, and the accumulation of inositol phosphates in cells labeled with myo-[2-3H]inositol was measured. Bioassay experiments showed that lysophosphatidylcholine inhibited the production and/or release of endothelium-derived relaxing factor from cultured endothelial cells. Lysophosphatidylcholine (5-20 micrograms/ml) induced a biphasic increase in [Ca2+]i, which consisted of a rapid increase followed by a sustained increase, and the initial component was a result of mobilization from intracellular Ca2+ stores without detectable synthesis of inositol 1,4,5-trisphosphates. Furthermore, lysophosphatidylcholine (5-20 micrograms/ml) dose-dependently inhibited both phosphoinositide hydrolysis and the increases in [Ca2+]i evoked by bradykinin. These results indicate that the impairment of endothelium-dependent relaxation induced by lysophosphatidylcholine is due to the inhibition of phosphoinositide hydrolysis and the subsequent increases in [Ca2+]i in endothelial cells. Lysophosphatidylcholine that accumulates in oxidized low density lipoprotein and atherosclerotic arteries may play an important role in the modification of endothelial function.
Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy
Authors: A.J.M. Ferreri, R. Dolcetti, M.-Q. Du, C. Doglioni, A. Giordano Resti, L.S. Politi, C. De Conciliis, J. Radford, F. Bertoni, E. Zucca, F. Cavalli, M. Ponzoni
Journal: Annals of Oncology (2007)
VARICOSE VEINS: THEIR MODERN TREATMENT BY SCLEROSING INJECTIONS: METHODS AND TECHNIQUE OF "SICARD AND GAUGIER" AS PRACTISED AT THE HOPITAL NECKER, PARIS
Authors: P. K. Murphy
Journal: BMJ (1929)

of Morgag-ii, and is preserved in the Patlhological Museum of the University' of Oxford.The patient made an uninterrupted recovery.This case has seemiied worthy of record ratlher on accoulnt of the rar-ity of the condition than of its clinical si^nifieance.I have failed to find aniy allusion to this lesion in the literature-of the subject, nor do a-y' cases appear to have been published recently, at least in this cousntry, America, or on the Continent.It wohlld be interesting to know whether pr-evious eases have been observed but not published.Thte description of the original colicLy pain w as suig- gestive of a uterine origin, andl was attriibuted to the ilncipient abortion, but the severe right-sidted( pain w-hich inicluced von-miting did not begin uintil the abortion was almiiost complete-that is, three weeks later-w*hen the uteruis colitained nothing but a fem necrotic fragments.It seems not improbable that this pain was dule to the stretching of the covering peritoneumiii produtced by the engorgemnent of the strangulated hyldatid.No cause wTas found for the torsion.The ovarian eysts were both simple follicular cysts following an old perio6phoritis, which had lproducecl on the right side a few incon.siderableadhesions; tlhe appendix presumably could have hiad nothilig to do witl the condition.
Forty-Year Psychiatric Outcomes Following Assessment for Internalizing Disorder in Adolescence
Authors: Ian Colman
Journal: American Journal of Psychiatry (2007)

Objective: The aim of this study was to define the long-term psychiatric outcomes of adolescent internalizing disorder in the general population, using data collected over 40 years from a national birth cohort. Method: A total of 3,279 members of the Medical Research Council National Survey of Health and Development (the 1946 British birth cohort) underwent assessments of psychiatric symptoms, primarily anxiety and depression, at ages 13 and 15. Adolescents who had internalizing disorder at both ages 13 and 15 and those who had internalizing disorder at one of the two ages were compared with mentally healthy adolescents on various psychiatric outcomes in adulthood (ages 26–53), including the prevalence of mental disorders, self-reported trouble with “nerves,” suicidal ideation, and treatment for psychiatric disorders. Results: About 70% of adolescents who had internalizing disorder at both ages 13 and 15 had mental disorder at age 36, 43, or 53, compared with about 25% of the mentally healthy adolescents. They were also more likely than healthy adolescents to have self-reported “nervous trouble” and to have been treated for psychiatric disorder during adulthood. None of these effects was apparent among subjects who had internalizing disorder at only one of the two adolescent assessments. Conclusions: The long-term psychiatric outcome for adolescents with persistent or recurrent internalizing disorder was poor, whereas the outcome for those who had a single episode was better than expected. The association between adolescent internalizing disorder and poor psychiatric outcomes in adulthood may be mediated by persistence or severity of symptoms in adolescence.