tbuckley/cabot-search huggingface dataset:
A Cohort Study of Thyroid Cancer and Other Thyroid Diseases After the Chornobyl Accident: Thyroid Cancer in Ukraine Detected During First Screening
Authors: Mykola D. Tronko, Geoffrey R. Howe, Tetyana I. Bogdanova, Andre C. Bouville, Ovsiy V. Epstein, Aaron B. Brill, Illya A. Likhtarev, Daniel J. Fink, Valentyn V. Markov, Ellen Greenebaum, Valery A. Olijnyk, Ihor J. Masnyk, Victor M. Shpak, Robert J. McConnell, Valery P. Tereshchenko, Jacob Robbins, Oleksandr V. Zvinchuk, Lydia B. Zablotska, Maureen Hatch, Nickolas K. Luckyanov, Elaine Ron, Terry L. Thomas, Paul G. Voillequé, Gilbert W. Beebe
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: The Chornobyl accident in 1986 exposed thousands of people to radioactive iodine isotopes, particularly 131 I; this exposure was followed by a large increase in thyroid cancer among those exposed as children and adolescents, particularly in Belarus, the Russian Federation, and Ukraine. Here we report the results of the first cohort study of thyroid cancer among those exposed as children and adolescents following the Chornobyl accident. Methods: A cohort of 32 385 individuals younger than 18 years of age and resident in the most heavily contaminated areas in Ukraine at the time of the accident was invited to be screened for any thyroid pathology by ultrasound and palpation between 1998 and 2000; 13 127 individuals (44%) were actually screened. Individual estimates of radiation dose to the thyroid were available for all screenees based on radioactivity measurements made shortly after the accident and on interview data. The excess relative risk per gray (Gy) was estimated using individual doses and a linear excess relative risk model. Results: Forty-five pathologically confirmed cases of thyroid cancer were found during the 1998–2000 screening. Thyroid cancer showed a strong, monotonic, and approximately linear relationship with individual thyroid dose estimate ( P <.001), yielding an estimated excess relative risk of 5.25 per Gy (95% confidence interval [CI] = 1.70 to 27.5). Greater age at exposure was associated with decreased risk of radiation-related thyroid cancer, although this interaction effect was not statistically significant. Conclusion: Exposure to radioactive iodine was strongly associated with increased risk of thyroid cancer among those exposed as children and adolescents. In the absence of Chornobyl radiation, 11.2 thyroid cancer cases would have been expected compared with the 45 observed, i.e., a reduction of 75% (95% CI = 50% to 93%). The study also provides quantitative risk estimates minimally confounded by any screening effects. Caution should be exercised in generalizing these results to any future similar accidents because of the potential differences in the nature of the radioactive iodines involved, the duration and temporal patterns of exposures, and the susceptibility of the exposed population.
Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity
Authors: J.-J. Yiin, B. Hu, M. J. Jarzynka, H. Feng, K.-W. Liu, J. Y. Wu, H.-I Ma, S.-Y. Cheng
Journal: Neuro-Oncology (2009)

Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and β-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2–Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2–Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.
Driving and Diabetes
Authors: Kenneth M. Adams
Journal: Diabetes Care (2003)

Cox et al. (1) alert us to an important issue for patients with diabetes, their families, and the motoring public. The data from this multicenter international study suggest that patients with type 1 diabetes are at what is potentially another order of risk for adverse events behind the wheel in comparison with type 2 diabetic patients and all patient spouses. It is noteworthy that there is an average 14-year age difference between the type 1 and type 2 diabetic groups, with the latter group more clearly middle-aged and subject to the decrements in vision (especially night vision), multitasking, and reaction time that characterize this time of life. This age difference could be seen as making the reported group differences on the survey all that more salient, or the difference might be a further confounding factor in interpreting this research. Statistical corrections cannot sufficiently dismiss the difference as an important issue (2,3).

The data here are consistent with what one might expect in terms of the essential feature of acute hypoglycemia that really defines the differences between the two types of diabetes in terms of driving risk. However, even this expectancy confirmation should be taken with caution, given that this is a study of self-reports conducted in the context of specialty medical care visits. It is also remarkable in that no subject …
Linkage Analysis of Candidate Loci for End-Stage Renal Disease due to Diabetic Nephropathy
Authors: Sudha K. Iyengar, Katherine A. Fox, Marlene Schachere, Fauzia Manzoor, Mary E. Slaughter, Adrian M. Covic, S. Mohammed Orloff, Patrick S. Hayden, Jane M. Olson, Jeffrey R. Schelling, John R. Sedor
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Diabetic nephropathy (DN), a major cause of ESRD, is undoubtedly multifactorial and is caused by environmental and genetic factors. To identify a genetic basis for DN susceptibility, we are collecting multiplex DN families in the Caucasian (CA) and African-American (AA) populations for whole genome scanning and candidate gene analysis. A candidate gene search of diabetic sibs discordantly affected, concordantly affected and concordantly unaffected for DN was performed with microsatellite markers in genomic regions suspected to harbor nephropathy susceptibility loci. Regions examined were at human chromosome 10p,10q (orthologous to the rat renal susceptibility Rf-1 locus), and at NPHS1 (nephrin), CD2AP, Wilms tumor (WT1), and NPHS2 (podocin) loci. Linkage analyses were conducted using model-free methods (SIBPAL, S.A.G.E.) for AA, CA, and the combined sample. Allele frequencies and the identity by descent sharing were estimated separately for AA and CA, and race was included as a covariate in the final linkage analysis. To date, we have collected 212 sib pairs from 46 CA and 50 AA families. The average age of diabetes onset was 46.8 yr versus 36.2 yr for CA and 39.5 yr versus 40.2 yr for AA, in males versus females respectively. Genotyping data were available for 106 sib pairs (43 CA, 63 AA) from 27 CA (44% male probands) and 38 AA families (43% male probands). Average AA and CA sibship size was 2.73. Singlepoint and multipoint linkage analyses indicate that marker D10S1654 on chromosome 10p is potentially linked to DN (CA only multipoint P = 4 × 10−3). Interestingly, the majority of the linkage evidence derives from the CA sib pairs. We are now adding sib pairs and increasing marker density on chromosome 10. We have excluded linkage with candidate regions for nephrin, CD2AP, WT1, and podocin in this sample. In conjunction with previous reports, our data support evidence for a DN susceptibility locus on chromosome 10. E-mail: [email protected]
A HapMap harvest of insights into the genetics of common disease
Authors: Teri A. Manolio, Lisa D. Brooks, Francis S. Collins
Journal: Journal of Clinical Investigation (2008)

The International HapMap Project was designed to create a genome-wide database of patterns of human genetic variation, with the expectation that these patterns would be useful for genetic association studies of common diseases. This expectation has been amply fulfilled with just the initial output of genome-wide association studies, identifying nearly 100 loci for nearly 40 common diseases and traits. These associations provided new insights into pathophysiology, suggesting previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. In addition, HapMap-based discoveries have shed new light on the impact of evolutionary pressures on the human genome, suggesting multiple loci important for adapting to disease-causing pathogens and new environments. In this review we examine the origin, development, and current status of the HapMap; its prospects for continued evolution; and its current and potential future impact on biomedical science.
Allele Frequency-Based and Polymorphism-Versus-Divergence Indices of Balancing Selection in a New Filtered Set of Polymorphic Genes in Plasmodium falciparum
Authors: L. I. Ochola, K. K. A. Tetteh, L. B. Stewart, V. Riitho, K. Marsh, D. J. Conway
Journal: Molecular Biology and Evolution (2010)

Signatures of balancing selection operating on specific gene loci in endemic pathogens can identify candidate targets of naturally acquired immunity. In malaria parasites, several leading vaccine candidates convincingly show such signatures when subjected to several tests of neutrality, but the discovery of new targets affected by selection to a similar extent has been slow. A small minority of all genes are under such selection, as indicated by a recent study of 26 Plasmodium falciparum merozoite-stage genes that were not previously prioritized as vaccine candidates, of which only one (locus PF10_0348) showed a strong signature. Therefore, to focus discovery efforts on genes that are polymorphic, we scanned all available shotgun genome sequence data from laboratory lines of P. falciparum and chose six loci with more than five single nucleotide polymorphisms per kilobase (including PF10_0348) for in-depth frequency–based analyses in a Kenyan population (allele sample sizes >50 for each locus) and comparison of Hudson–Kreitman–Aguade (HKA) ratios of population diversity (π) to interspecific divergence (K) from the chimpanzee parasite Plasmodium reichenowi. Three of these (the msp3/6-like genes PF10_0348 and PF10_0355 and the surf4.1 gene PFD1160w) showed exceptionally high positive values of Tajima's D and Fu and Li's F indices and have the highest HKA ratios, indicating that they are under balancing selection and should be prioritized for studies of their protein products as candidate targets of immunity. Combined with earlier results, there is now strong evidence that high HKA ratio (as well as the frequency-independent ratio of Watterson's θ/K) is predictive of high values of Tajima's D. Thus, the former offers value for use in genome-wide screening when numbers of genome sequences within a species are low or in combination with Tajima's D as a 2D test on large population genomic samples.
CD44 activation in mature B-cell malignancies by a novel recurrent IGH translocation
Authors: Xiao-Tong Hu, Yun-Wen Chen, Anthony C. T. Liang, Wing-Yan Au, Kai-Yau Wong, Thomas S. K. Wan, Michelle L. Y. Wong, Lijun Shen, Ka-Kui Chan, Tianhuan Guo, Kent-Man Chu, Qian Tao, Chor-Sang Chim, Florence Loong, William W. L. Choi, Liwei Lu, Chi-Chiu So, Li Chong Chan, Yok-Lam Kwong, Raymond H. S. Liang, Gopesh Srivastava
Journal: Blood (2010)
Revised Risk Classification for Pediatric Extracranial Germ Cell Tumors Based on 25 Years of Clinical Trial Data From the United Kingdom and United States
Authors: A. Lindsay Frazier, Juliet P. Hale, Carlos Rodriguez-Galindo, Ha Dang, Thomas Olson, Matthew J. Murray, James F. Amatruda, Claire Thornton, G. Suren Arul, Deborah Billmire, Furqan Shaikh, Farzana Pashankar, Sara Stoneham, Mark Krailo, James C. Nicholson
Journal: Journal of Clinical Oncology (2014)

Purpose To risk stratify malignant extracranial pediatric germ cell tumors (GCTs). Patients and Methods Data from seven GCT trials conducted by the Children's Oncology Group (United States) or the Children's Cancer and Leukemia Group (United Kingdom) between 1985 and 2009 were merged to create a data set of patients with stage II to IV disease treated with platinum-based therapy. A parametric cure model was used to evaluate the prognostic importance of age, tumor site, stage, histology, tumor markers, and treatment regimen and estimate the percentage of patients who achieved long-term disease-free (LTDF) survival in each subgroup of the final model. Validation of the model was conducted using the bootstrap method. Results In multivariable analysis of 519 patients with GCTs, stage IV disease (P = .001), age ≥ 11 years (P &lt; .001), and tumor site (P &lt; .001) were significant predictors of worse LTDF survival. Elevated alpha-fetoprotein (AFP) ≥ 10,000 ng/mL was associated with worse outcome, whereas pure yolk sac tumor (YST) was associated with better outcome, although neither met criteria for statistical significance. The analysis identified a group of patients age &gt; 11 years with either stage III to IV extragonadal tumors or stage IV ovarian tumors with predicted LTDF survival &lt; 70%. A bootstrap procedure showed retention of age, tumor site, and stage in &gt; 94%, AFP in 12%, and YST in 27% of the replications. Conclusion Clinical trial data from two large national pediatric clinical trial organizations have produced a new evidence-based risk stratification of malignant pediatric GCTs that identifies a poor-risk group warranting intensified therapy.
Parathyroid Hormone-Related Protein Induces Cachectic Syndromes without Directly Modulating the Expression of Hypothalamic Feeding-Regulating Peptides
Authors: Hirofumi Hashimoto, Yumiko Azuma, Makoto Kawasaki, Hiroaki Fujihara, Etsuro Onuma, Hisafumi Yamada-Okabe, Yoh Takuwa, Etsuro Ogata, Yoichi Ueta
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia of malignancy (HHM) and concurrent anorexia and wasting. Because changes in the expression of hypothalamic feeding-regulating peptides can directly affect appetites and thereby can cause anorexia and wasting, we addressed whether the cachectic syndromes induced by PTHrP rely on the action of hypothalamic feeding-regulating peptides. Experimental Design: Rats were inoculated with a LC-6 human cancer xenograft that secreted PTHrP, and the mRNA levels of the hypothalamic feeding-regulating peptide genes and serum leptin levels were examined before and after the development of HHM by in situ hybridization histochemistry and ELISA, respectively. Some rats were given the anti-PTHrP antibody. Results and Conclusion: The mRNA levels for the orexigenic peptides, such as the agouti-related protein and the neuropeptide Y in the arcuate nucleus (Arc), were significantly increased after the development of HHM, whereas the mRNA levels for the anorexigenic peptides, such as the proopiomelanocortin in the Arc, the cocaine and amphetamine-regulated transcript in the Arc, and the corticotropin-releasing factor in the paraventricular nucleus, were significantly decreased after the development of HHM. Plasma leptin levels were also reduced in cachectic rats, and the administration of anti-PTHrP antibody to the cachectic rats not only improved the cachectic symptoms but also restored the mRNA levels of these orexigenic and anorexigenic peptides, except for orexin. Thus, PTHrP induces HHM and concurrent cachectic syndromes by mechanisms other than directly modulating the leptin or hypothalamic feeding-regulated peptides.
Does the effectiveness of pulmonary rehabilitation vary in patients with different baseline severity of symptoms classified by MRC grade
Authors: Emma Tucker, Rachel Lardner, Joanne Riley, Maxine Hardinge
Journal: European Respiratory Journal (2013)

Introduction  Pulmonary rehabilitation (PR) as a treatment for chronic lung disease can result in clinically meaningful improvements in health related quality of life (HRQL), and exercise capacity. UK guidelines recommend referral of patients with MRC breathlessness grades 3 and over. However, patients with MRC grade 5 breathlessness are often housebound and less likely to be referred for PR. This study examined whether similar improvements in HRQL and exercise capacity were seen in patients with different MRC grades.  Methods  490 patients were enrolled in a 7 week PR programme between April 2011 and March 2012. All patients completed Incremental Shuttle Walk Test (ISWT) to measure exercise tolerance and St Georges Respiratory Questionnaire (SGRQ) to measure health related quality of life, pre and post PR. The percentage of patients achieving the minimally important clinical difference (MICD) for ISWT (47.5 metres) and SGRQ (4 points) were calculated for each MRC group.  Results  383 patients (78%) completed PR, 218 (57%) male: of these 179 (47%) had baseline MRC grade 3 (mean age 70.3), 173 (45%) MRC 4 (mean age 70), and 31 (8%) MRC 5 (mean age 75.3). Fewer patients in MRC grade 5 group (30%) achieved MICD for exercise capacity compared with MRC grade 3 (53%) and MRC grade 4 (61%): but a similar proportion of MRC grade 5 patients (48%) achieved MCID for HRQL measures (52% for both MRC grades 3 and 4).  Conclusion  Exercise capacity improves most after PR in patients with less breathlessness at baseline: however, even patients with severe breathlessness achieve similar clinically significant improvements in HRQL and should be referred for PR.
Oral and visual language are not processed in like fashion: Constraints on the products of the SOC
Authors: Christophe Parisse, Henri Cohen
Journal: Behavioral and Brain Sciences (2002)

The SOC framework does not take into account the fact that the oral modality consists of purely transient data, which is not the case for the other modalities. This, however, has important consequences on the nature of oral and written language, on language consciousness, on child language development, and on the history of linguistics.
Medical thoracoscopy - Patient and procedure characteristics
Authors: Arun Lakhanpal, Apollinaris Kwok, Sizheng Zhao, Christopher James Warburton, Biswajit Chakrabarti
Journal: European Respiratory Journal (2013)

Medical Thoracoscopy(MT) is a sensitive diagnostic and therapeutic tool for pleural disease1,2. Patient selection, premedication, analgesia and sedation are largely the operator’s choice1. We studied the case records of 169 patients who underwent rigid MT for diagnosis or pleurodesis at University Hospital Aintree between December 2003 and October 2012. Data was collected on Patient characteristics(Table1), Procedure details including doses of analgesia/sedation used and complications(Table2)

View this table:

Patient Characteristics





View this table:

Thoracoscopy details and complications





Conclusion-MT can be safely performed on patients with a wide range of Performance status and FEV1 as in our study population. Further studies are needed to define the patient and procedure characteristics to minimise failure rates and complications.

References:

1.Local Anaesthetic Thoracoscopy–BTS Pleural Disease Guideline 2010 . Najib M Rahman,Nabeel J Ali,Gail Brown,et al.

2.The role of thoracoscopy in the evaluation and management of pleural effusions.Boutin C,Astoul P,Seitz B.Lung.December 1990;Volume168,Issue 1 Suppl,pp1113-1121.
Computed tomographic emphysema distribution: relationship to clinical features in a cohort of smokers
Authors: G. Mair, J. J. Miller, D. McAllister, J. Maclay, M. Connell, J. T. Murchison, W. MacNee
Journal: European Respiratory Journal (2008)

Computed tomography (CT) scanning allows precise assessment of both the extent and distribution of emphysema. There has been little work on the relationship between the distribution of emphysema and clinical features of the disease. The current study investigated the association between clinical features and distribution of emphysema. A total of 129 patients with smoking-related chronic obstructive pulmonary disease underwent CT assessment of the extent and distribution of their emphysema (core/rind and upper/lower zone predominance). Emphysema was found predominantly in the upper/core zone and this distribution was related to the extent of disease. Core predominance was associated with lower forced expiratory volume in one second (FEV(1)), FEV(1)/forced vital capacity ratio and body mass index (BMI); and with higher BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) index and Medical Research Council dyspnoea score. Upper-zone predominance was associated with female sex and an increased total St George's Respiratory Questionnaire score. Using multiple linear regression age, sex and whole lung emphysema severity were independently associated with core/rind distribution, while sex and whole lung emphysema severity were independently related to upper/lower distribution. Distribution of emphysema related best to clinical features when divided into core/rind predominance. However, the effects were not independent of the extent of emphysema. Increased age and female sex were related to disease distribution independent of emphysema severity. These findings may be related to differences in development of emphysema.
The V beta complementarity determining region 1 of a major histocompatibility complex (MHC) class I-restricted T cell receptor is involved in the recognition of peptide/MHC I and superantigen/MHC II complex.
Authors: M Bellio, Y C Lone, O de la Calle-Martin, B Malissen, J P Abastado, P Kourilsky
Journal: The Journal of Experimental Medicine (1994)

We investigated the role of the complementarity determining region 1 (CDR1) of T cell receptor (TCR) beta chain both in antigen/major histocompatibility complex I (MHC I) and in superantigen (SAg)/MHC II complex recognition. Residues 26 to 31 of the V beta 10 domain of a TCR derived from an H-2Kd-restricted cytotoxic clone were individually changed to alanine, using site-directed mutagenesis, and the mutated TCR beta chains were transfected along with the wild-type TCR alpha chain into a TCR alpha-beta-T hydridoma. These mutations affected antigen/H-2Kd complex recognition, although to a different extent, as estimated by interleukin 2 production. Certain mutations also affected differently the recognition of two Staphylococcal toxins, exfoliative toxin and Staphylococcal enterotoxin C2, presented by HLA-DR1. Whereas mutation of residues D30 or T31 affect the recognition of both toxins, residues T26, L27, and H29 are critical for the recognition of only one of the SAgs. These observations demonstrate the participation of the CDR1 region in the recognition of peptide/MHC class I as well as SAg/MHC II complexes.