tbuckley/cabot-search huggingface dataset:
Radiation Therapy After Mastectomy Between 1991 and 1999 in Elderly Women: Response to Clinical Trial Information
Authors: Rinaa S. Punglia, Jane C. Weeks, Bridget A. Neville, Craig C. Earle
Journal: Journal of Clinical Oncology (2006)

No systematic study has analyzed the changing patterns of use of postmastectomy radiation therapy (PMRT) during the period of information dissemination regarding the benefit of radiation therapy in this setting. We sought to study the receipt of PMRT in elderly women in this period, using a population-based cohort of women with breast cancer.Using data from the linked Surveillance, Epidemiology, and End Results-Medicare database, we analyzed the use of radiation therapy between 1991 and 1999 in 19,699 women with stage I to III breast cancer who received mastectomy as definitive surgery. Multivariable logistic regression was used to investigate the association of diagnosis year and the use of PMRT, after controlling for clinical and sociodemographic factors.During the entire period studied, 2,160 (11.0%) patients treated with mastectomy received PMRT. The use of PMRT significantly increased in women diagnosed in 1996 (odds ratio [OR], 1.26; P = .04), 1997 (OR, 1.70; P < .0001), 1998 (OR, 1.57; P < .0001), and 1999 (OR, 1.77; P < .0001), relative to those diagnosed in 1991 after controlling for cancer, and sociodemographic and treatment characteristics. There were significant differences in the temporal trends of radiation use among different regions of the country (P < .0001), and between teaching versus nonteaching institutions (P = .04).The use of PMRT in elderly women increased significantly during the period of data dissemination about its efficacy; however, the trends in adoption varied among different practice settings.
Insulin Sensitivity in the Offspring of Women With Type 1 and Type 2 Diabetes
Authors: Wendy A. Hunter, Tim Cundy, Diana Rabone, Paul L. Hofman, Mark Harris, Fiona Regan, Elizabeth Robinson, Wayne S. Cutfield
Journal: Diabetes Care (2004)

To determine if insulin sensitivity is altered in prepubertal offspring exposed to a diabetic intrauterine environment.Fifteen control children, 17 offspring of type 1 diabetic women, and 10 offspring of type 2 diabetic women, aged between 5 and 10 years, underwent a frequently sampled intravenous glucose tolerance test (FSIGTT). Weight and height were measured, and body composition was calculated using bioelectrical impedance. Bergman's minimal model was applied to the glucose and insulin measurements to obtain values for insulin sensitivity (Si), acute insulin response (AIR), and glucose effectiveness (Sg).Si was lowest in the offspring of type 2 diabetic mothers, and AIR was highest in this group, although neither of these changes reached significance (Si, P = 0.2, and AIR, P = 0.3). Offspring of type 2 diabetic mothers had higher BMI SD scores (P = 0.004) and percentage fat mass (P = 0.002) than the children in the other two groups. The BMI SD score and percentage fat mass in the subjects, as well as maternal insulin dose, were negatively correlated with offspring insulin sensitivity.Intrauterine exposure to hyperglycemia by itself was not associated with alterations in glucose regulation in prepubertal offspring. Children of mothers with type 2 diabetes, however, were overweight, and they had a tendency for a reduced Si. The combined effect of genetic and postnatal environmental factors, rather than prenatal exposure to hyperglycemia, may place this group at risk for developing impaired glucose tolerance in later life.
A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development
Authors: Alyson Ashe, Daniel K Morgan, Nadia C Whitelaw, Timothy J Bruxner, Nicola K Vickaryous, Liza L Cox, Natalie C Butterfield, Carol Wicking, Marnie E Blewitt, Sarah J Wilkins, Gregory J Anderson, Timothy C Cox, Emma Whitelaw
Journal: Genome biology (2008)

Abstract Background Some years ago we established an N-ethyl-N-nitrosourea screen for modifiers of transgene variegation in the mouse and a preliminary description of the first six mutant lines, named MommeD1-D6 , has been published. We have reported the underlying genes in three cases: MommeD1 is a mutation in SMC hinge domain containing 1 ( Smchd1 ), a novel modifier of epigenetic gene silencing; MommeD2 is a mutation in DNA methyltransferase 1 ( Dnmt1 ); and MommeD4 is a mutation in Smarca 5 ( Snf2h ), a known chromatin remodeler. The identification of Dnmt1 and Smarca5 attest to the effectiveness of the screen design. Results We have now extended the screen and have identified four new modifiers, MommeD7 - D10 . Here we show that all ten MommeD s link to unique sites in the genome, that homozygosity for the mutations is associated with severe developmental abnormalities and that heterozygosity results in phenotypic abnormalities and reduced reproductive fitness in some cases. In addition, we have now identified the underlying genes for MommeD5 and MommeD10 . MommeD5 is a mutation in Hdac1 , which encodes histone deacetylase 1, and MommeD10 is a mutation in Baz1b (also known as Williams syndrome transcription factor ), which encodes a transcription factor containing a PHD-type zinc finger and a bromodomain. We show that reduction in the level of Baz1b in the mouse results in craniofacial features reminiscent of Williams syndrome. Conclusions These results demonstrate the importance of dosage-dependent epigenetic reprogramming in the development of the embryo and the power of the screen to provide mouse models to study this process.
Constraints on the evolution of plastid introns: the group II intron in the gene encoding tRNA-Val(UAC).
Authors: G H Learn, J S Shore, G R Furnier, G Zurawski, M T Clegg
Journal: Molecular Biology and Evolution (1992)

The evolution of the group II intron in the plastid gene encoding tRNA(Val)UAC (trnV) from seven plant taxa was studied by aligning secondary and other structural features. Levels of evolutionary divergence between six angiosperms and a liverwort, Marchantia polymorpha, were compared for the six domains commonly demonstrated for group II introns and were shown to be statistically heterogeneous. Evolutionary rates varied substantially among various domains and other features. Domain II showed the highest evolutionary rate, approaching the synonymous substitution rate reported for cpDNA-encoded genes, while domain VI and the helix and loop region bearing EBS1 evolved at rates similar to those for nonsynonymous substitutions of a number of cpDNA-encoded genes. The minimum free-energy structure of domain I varied among the seven taxa, suggesting that possible protein-RNA or tertiary interactions are important for intron processing.
Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3
Authors: German Ott, Tiemo Katzenberger, Andreas Lohr, Steffi Kindelberger, Thomas Rüdiger, Martin Wilhelm, Jörg Kalla, Andreas Rosenwald, Justus G. Müller, M. Michaela Ott, Hans Konrad Müller-Hermelink
Journal: Blood (2002)
Effect of cigarette smoking, pulmonary inflammation, and lung disease on concentrations of carcinoembryonic antigen in serum and secretions.
Authors: R A Stockley, J Shaw, A G Whitfield, T P Whitehead, C A Clarke, D Burnett
Journal: Thorax (1986)

A specific radioimmunoassay for carcinoembryonic antigen was used to investigate aspects of its measurement in lung disease. The results confirm that serum carcinoembryonic antigen concentrations are higher in healthy smokers and patients with chronic obstructive bronchitis than in healthy non smokers (p less than 0.01). Corticosteroid treatment reduced the concentration in nine patients with bronchitis (p less than 0.05). Other inflammatory lung diseases (bronchiectasis, pneumonia, fibrosing alveolitis) are not associated with a raised serum carcinoembryonic antigen concentration. The sputum concentrations were about 100 times those found in serum and there was a positive correlation (r = 0.611 2p less than 0.01) between the concentrations in sputum and serum in patients with bronchitis. No preferential rise in sputum concentration was found in current smokers or patients with lung carcinoma (n = 16). A higher ratio of carcinoembryonic antigen to albumin concentration (p less than 0.05) was, however, found in lavage fluid obtained from the tumour site than in fluid from "normal" lung in the same patients, suggesting an increase in carcinoembryonic antigen secretion in the vicinity of the tumour. Despite this "local" effect the sputum concentration does not, however, appear to be a useful marker of lung carcinoma and the measurement could not be used as a screening test.
Infection and irritability
Authors: R Lea
Journal: Gut (2002)

A proportion of patients with irritable bowel syndrome report an apparent association between the onset of symptoms and a dysenteric illness

Chaudhary and Truelove were amongst the first to recognise that a proportion of patients with irritable bowel syndrome (IBS) report an apparent association between the onset of symptoms and a dysenteric illness.1 The concept of “post-dysenteric IBS” (PD-IBS) has now been widely accepted with claims suggesting that it accounts for anything up to 25% of the totality of the condition. However, careful questioning of these patients sometimes, but not always, suggests that they may have had a “forme fruste” of the disorder before their infection, raising the possibility that there may be two forms of the illness, one being an exacerbation of a pre-existing disorder and another where the condition appears to arise de novo. Ultimately, issues surrounding the natural history of PD-IBS will only be resolved by detailed prospective and retrospective studies, such as the one reported by Neal and colleagues2 in this issue of Gut [see page 410] .

Given that dysentery leads to irritable bowel symptoms, what mechanisms might be responsible? Do the dysenteric organisms cause the problem directly, and if so, are some more noxious than others? Alternatively, does the resulting diarrhoea lead to a form of non-specific sensitisation? …
Phase III Study of Two Different Dosing Schedules of Erythropoietin in Anemic Patients With Cancer
Authors: David P. Steensma, Roy Molina, Jeff A. Sloan, Daniel A. Nikcevich, Paul L. Schaefer, Kendrith M. Rowland, Todor Dentchev, Paul J. Novotny, Loren K. Tschetter, Steven R. Alberts, Thomas F. Hogan, Amy Law, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2006)

Purpose To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia. Patients and Methods Eligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks. Results Three hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a ≥ 2 or ≥ 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent. Conclusion After three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.
Expansion and Intragenic Homogenization of Spider Silk Genes since the Triassic: Evidence from Mygalomorphae (Tarantulas and Their Kin) Spidroins
Authors: Jessica E. Garb, Teresa DiMauro, Randolph V. Lewis, Cheryl Y. Hayashi
Journal: Molecular Biology and Evolution (2007)

Spiders spin a diverse array of silk fibers that are predominately composed of repetitive proteins (spidroins) encoded by a gene family. Characterization of this gene family has focused on spidroins synthesized by the Araneomorphae (true spiders), whereas only a single sequence is known from the Mygalomorphae (tarantulas and their kin). To better understand the diversity and evolution of the spidroin gene family, we surveyed the silk gland transcriptomes of 4 divergent mygalomorph species. Through expressed sequence tag screening and probing of silk gland cDNA libraries, we discovered 6 novel mygalomorph spidroins and an ∼8-kb cDNA of the previously reported Euagrus chisoseus fibroin 1. Mygalomorph spidroin cDNAs encode tandem iterations of sequence repeats, followed by a nonrepetitive carboxy-terminal domain. Though highly homogenized at the nucleotide level within a cDNA (89–100% identical), these repeats exhibit extensive variation across spidroins, consistent with intragenic repeats evolving in concert. Extreme homogeneity of intragenic repeats is also characteristic of araneomorph spidroins, suggesting that modular architecture and its maintenance through concerted evolution have persisted since the mygalomorph/araneomorph split (≥240 MYA). Phylogenetic analyses of C-terminal sequences grouped all mygalomorph spidroins, except Aliatypus fibroin 1, in a clade. Aliatypus fibroin 1 was instead more closely related to a subset of araneomorph spidroins, including those used in prey wrapping. Our results suggest that spidroin paralogs existed prior to the divergence of mygalomorphs and araneomorphs, followed by a far greater expansion of this gene family in araneomorphs, paralleling the dramatic functional diversification of their silk gland anatomy.
Absence of an association between HLA-DRB1*04 and rheumatoid arthritis in newly diagnosed cases from the community.
Authors: W Thomson, L Pepper, A Payton, D Carthy, D Scott, W Ollier, A Silman, D Symmons
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine HLA-DR4 and DR1 allele frequencies in a series of patients with newly diagnosed early inflammatory arthritis. METHODS--HLA-DR1 and DR4 frequencies were determined by oligonucleotide typing of 208 patients classified as having either rheumatoid arthritis (RA) or undifferentiated inflammatory polyarthritis. RESULTS--The frequency of occurrence of DR4 in these patients with RA did not differ significantly from that in controls in the United Kingdom (42 v 37%). HLA-DR1 was increased in the group with inflammatory polyarthritis (25 v 18%). CONCLUSIONS--The frequency of DR4 is not increased in newly diagnosed community based patients with RA. This supports the hypothesis that DR4 is less important as a marker for susceptibility to RA than it is for disease persistence or severity.
Problem Adaptation Therapy for Older Adults With Major Depression and Cognitive Impairment
Authors: Dimitris N. Kiosses, Lisa D. Ravdin, James J. Gross, Patrick Raue, Nabil Kotbi, George S. Alexopoulos
Journal: JAMA Psychiatry (2014)

IMPORTANCE Problem adaptation therapy (PATH) is a treatment for older adults with major depression, cognitive impairment (from mild cognitive deficits to moderate dementia), and disability.Antidepressants have limited efficacy in this population and psychosocial interventions are inadequately investigated.OBJECTIVE To test the efficacy of 12-week PATH vs supportive therapy for cognitively impaired patients (ST-CI) in reducing depression and disability in 74 older adults with major depression, cognitive impairment, and disability. DESIGN, SETTING, AND PARTICIPANTSA randomized clinical trial at the Weill Cornell Institute of Geriatric Psychiatry from April 1, 2006, to September 31, 2011.Interventions were administered at the participants' homes.Participants included 74 older individuals (age Ն65 years) with major depression and cognitive impairment to the level of moderate dementia.They were recruited through collaborating community agencies of Weill Cornell Institute of Geriatric Psychiatry and were randomly assigned to 12 weekly sessions of PATH or ST-CI (14.8% attrition rate).INTERVENTIONS Home-delivered PATH vs home-delivered ST-CI.Problem adaptation therapy integrates a problem-solving approach with compensatory strategies, environmental adaptations, and caregiver participation to improve patients' emotion regulation.Supportive therapy for cognitively impaired patients focuses on expression of affect, understanding, and empathy.MAIN OUTCOMES AND MEASURES Mixed-effects models for longitudinal data compared the efficacy of PATH with that of ST-CI in reducing depression (Montgomery-Asberg Depression Rating Scale) and disability (World Health Organization Disability Assessment Schedule II) during 12 weeks of treatment.RESULTS Participants in PATH had significantly greater reduction in depression (Cohen d, 0.60; 95% CI, 0.13-1.06;treatment × time, F 1,179 = 8.03; P = .005)and disability (Cohen d, 0.67; 95% CI, 0.20-1.14;treatment × time, F 1,169 = 14.86;P = .001)than ST-CI participants during the 12-week period (primary outcomes).Furthermore, PATH participants had significantly greater depression remission rates than ST-CI participants (37.84% vs 13.51%; χ 2 = 5.74; P = .02;number needed to treat = 4.11) (secondary outcome). CONCLUSIONS AND RELEVANCEProblem adaptation therapy was more efficacious than ST-CI in reducing depression and disability.Problem adaptation therapy may provide relief to a large group of depressed and cognitively impaired older adults who have few treatment options.
Rapamycin Ameliorates PKD Resulting from Conditional Inactivation of Pkd1
Authors: Jonathan M. Shillingford, Klaus B. Piontek, Gregory G. Germino, Thomas Weimbs
Journal: Journal of the American Society of Nephrology (2010)

Aberrant activation of the mammalian target of rapamycin (mTOR) pathway occurs in polycystic kidney disease (PKD). mTOR inhibitors, such as rapamycin, are highly effective in several rodent models of PKD, but these models result from mutations in genes other than Pkd1 and Pkd2, which are the primary genes responsible for human autosomal dominant PKD. To address this limitation, we tested the efficacy of rapamycin in a mouse model that results from conditional inactivation of Pkd1. Mosaic deletion of Pkd1 resulted in PKD and replicated characteristic features of human PKD including aberrant mTOR activation, epithelial proliferation and apoptosis, and progressive fibrosis. Treatment with rapamycin was highly effective: It reduced cyst growth, preserved renal function, inhibited epithelial cell proliferation, increased apoptosis of cyst-lining cells, and inhibited fibrosis. These data provide in vivo evidence that rapamycin is effective in a human-orthologous mouse model of PKD.
Chart helps with calculation of dose of adrenaline for children
Authors: J. Stuart
Journal: BMJ (1995)

teaching, intraosseous access may be secured without difficulty and should be considered in any paediatric emergency in which intravenous access cannot be secured promptly.Bolus and infusion doses of adrenaline can be given safely by this route, as can other pharmacological agents recommended in anaphylaxis.In children with signs of upper airway ob- struction caused by laryngeal mucosal oedema, nebulised adrenaline may lead to prompt resolution of stridor.5It should be given as a dose of either 0 05 ml of a 2-25% (racemic) solution/kg diluted to 2 ml with normal saline or, more conveniently, as 0 5 ml of a 1/1000 solution/kg (to a maximum of 5 ml).The child whose clinical history prompted Fisher's review would probably have benefited from this treatment.Finally, in both his article and the summary in "This week in BMY" Fisher states that oxygen should be given in severe anaphylaxis.We prefer the recommendations of the Association of Anaes- thetists of Great Britain and Ireland that oxygen should be given in all cases ofanaphylaxis regardless of the initial severity.3Hypoxaemia will develop quickly if a patient suddenly develops airway obstruction as a late complication of an initially mild attack.
Imaging the Urokinase Plasminongen Activator Receptor in Preclinical Breast Cancer Models of Acquired Drug Resistance
Authors: Aaron M. LeBeau, Natalia Sevillano, Mandy L. King, Sai Duriseti, Stephanie T. Murphy, Charles S. Craik, Laura L. Murphy, Henry F. VanBrocklin
Journal: Theranostics (2014)

Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications.
Cholesterol lowering margarine may not be useful in healthy fat modified diet
Authors: C. van Heyningen
Journal: BMJ (1999)

EDITOR—A new margarine spread that reduces intestinal absorption of cholesterol was launched in the United Kingdom in April.1 Benecol contains stanol esters derived from wood pulp. National press advertisements indicate that it reduces serum concentrations of low density lipoprotein cholesterol by an average of 14% when taken as three servings daily …