tbuckley/cabot-search huggingface dataset:
Birds of a Feather: Pigeon Head Crest Findings Extend to Domesticated Doves
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2015)

Evolutionary biologist Michael Shapiro and his team made international headlines in 2013 when they found that a prominent change in pigeon plumage, head crests, could be traced to a mutation in a single gene. Now, in the new advanced online edition of Molecular Biology and Evolution (Vickrey et al. 2015), the research team has found an almost exact repeat in the evolutionary playbook. A mutation in the same gene, EphB2, has led to a similar result in domesticated ringneck doves. The mutation causes the feathers on the back of the head and neck to grow up toward the head in a striking look. Domesticated rock pigeons have more than 300 varieties that have been bred and chosen for their prized looks and vibrant feather colors. The head-crested birds had one version of the gene, a single mutation that made an aberrant protein (Arg758Cys) responsible for the feather difference between them and uncrested birds. The researchers performed DNA analyses from 50 crested and 75 uncrested ringneck doves and found a different mutation in the same gene, which led to a single Gly636Arg amino acid substitution. In both cases, a single DNA base change hinders normal protein function by changing an amino acid at a crucial spot, causing the feather to swoop up toward the head rather than tuck neatly down. “Crested birds from both species have mutations in the same gene, and even in the same functional part of the gene,” said Shapiro. “This suggests that only a limited number of genes—perhaps only genes in the EphB2 pathway—can cause crest formation without causing other problems that affect survival of the embryo or adult. Studying other species will help us understand if this same genetic mechanism is used repeatedly throughout crested bird species, or if it’s a mechanism that’s limited to the pigeon and dove family.” Given that the ringneck dove is a domesticated species that last shared a common ancestor with the rock pigeon 23–35 Ma, the study shows that the same gene can be implicated as a prime driver of feather variation in completely different species, separated over a great evolutionary distance. “We know that many genes are involved in feather development, so it’s rather remarkable that the same gene appears to control the same trait in two distantly related species,” said Shapiro. Next, armed with new DNA banks of bird species, Shapiro’s team will examine how far and wide this unique evolutionary twist may be found among other bird species and wild populations.
Evaluation of HER2, p53, bcl-2, topoisomerase II-α, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes
Authors: F. Cardoso, A. Di Leo, D. Larsimont, D. Gancberg, G. Rouas, S. Dolci, F. Ferreira, M. Paesmans, M. Piccart
Journal: Annals of Oncology (2001)
Specific IgE reactivity to Tri a 36 in children with wheat food allergy
Authors: Alexandra Baar, Sandra Pahr, Claudia Constantin, Stavroula Giavi, Alkisti Manoussaki, Nikolaos G. Papadopoulos, Christof Ebner, Adriano Mari, Susanne Vrtala, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2013)
<i>DNMT3A</i>Mutations in Acute Myeloid Leukemia
Authors: Timothy J. Ley, Li Ding, Matthew J. Walter, Michael D. McLellan, Tamara Lamprecht, David E. Larson, Cyriac Kandoth, Jacqueline E. Payton, Jack Baty, John Welch, Christopher C. Harris, Cheryl F. Lichti, R. Reid Townsend, Robert S. Fulton, David J. Dooling, Daniel C. Koboldt, Heather Schmidt, Qunyuan Zhang, John R. Osborne, Ling Lin, Michelle O'Laughlin, Joshua F. McMichael, Kim D. Delehaunty, Sean D. McGrath, Lucinda A. Fulton, Vincent J. Magrini, Tammi L. Vickery, Jasreet Hundal, Lisa L. Cook, Joshua J. Conyers, Gary W. Swift, Jerry P. Reed, Patricia A. Alldredge, Todd Wylie, Jason Walker, Joelle Kalicki, Mark A. Watson, Sharon Heath, William D. Shannon, Nobish Varghese, Rakesh Nagarajan, Peter Westervelt, Michael H. Tomasson, Daniel C. Link, Timothy A. Graubert, John F. DiPersio, Elaine R. Mardis, Richard K. Wilson
Journal: New England Journal of Medicine (2010)

The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown.Using massively parallel DNA sequencing, we identified a somatic mutation in DNMT3A, encoding a DNA methyltransferase, in the genome of cells from a patient with AML with a normal karyotype. We sequenced the exons of DNMT3A in 280 additional patients with de novo AML to define recurring mutations.A total of 62 of 281 patients (22.1%) had mutations in DNMT3A that were predicted to affect translation. We identified 18 different missense mutations, the most common of which was predicted to affect amino acid R882 (in 37 patients). We also identified six frameshift, six nonsense, and three splice-site mutations and a 1.5-Mbp deletion encompassing DNMT3A. These mutations were highly enriched in the group of patients with an intermediate-risk cytogenetic profile (56 of 166 patients, or 33.7%) but were absent in all 79 patients with a favorable-risk cytogenetic profile (P<0.001 for both comparisons). The median overall survival among patients with DNMT3A mutations was significantly shorter than that among patients without such mutations (12.3 months vs. 41.1 months, P<0.001). DNMT3A mutations were associated with adverse outcomes among patients with an intermediate-risk cytogenetic profile or FLT3 mutations, regardless of age, and were independently associated with a poor outcome in Cox proportional-hazards analysis.DNMT3A mutations are highly recurrent in patients with de novo AML with an intermediate-risk cytogenetic profile and are independently associated with a poor outcome. (Funded by the National Institutes of Health and others.).
Validation of the 12-Gene Colon Cancer Recurrence Score in NSABP C-07 As a Predictor of Recurrence in Patients With Stage II and III Colon Cancer Treated With Fluorouracil and Leucovorin (FU/LV) and FU/LV Plus Oxaliplatin
Authors: Greg Yothers, Michael J. O'Connell, Mark Lee, Margarita Lopatin, Kim M. Clark-Langone, Carl Millward, Soonmyung Paik, Saima Sharif, Steven Shak, Norman Wolmark
Journal: Journal of Clinical Oncology (2013)

Accurate assessments of recurrence risk and absolute treatment benefit are needed to inform colon cancer adjuvant therapy. The 12-gene Recurrence Score assay has been validated in patients with stage II colon cancer from the Cancer and Leukemia Group B 9581 and Quick and Simple and Reliable (QUASAR) trials. We conducted an independent, prospectively designed clinical validation study of Recurrence Score, with prespecified end points and analysis plan, in archival specimens from patients with stage II and III colon cancer randomly assigned to fluorouracil (FU) or FU plus oxaliplatin in National Surgical Adjuvant Breast and Bowel Project C-07.
Effect of Nonuniform Muscle Contraction on Sustainability and Frequency of Triggered Arrhythmias in Rat Cardiac Muscle
Authors: Masahito Miura, Taichi Nishio, Taiki Hattori, Naomi Murai, Bruno D. Stuyvers, Chiyohiko Shindoh, Penelope A. Boyden
Journal: Circulation (2010)

Arrhythmias are benign or lethal, depending on their sustainability and frequency. To determine why lethal arrhythmias are prone to occur in diseased hearts, usually characterized by nonuniform muscle contraction, we investigated the effect of nonuniformity on sustainability and frequency of triggered arrhythmias.Force, membrane potential, and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in 51 rat ventricular trabeculae. Nonuniform contraction was produced by exposing a restricted region of muscle to a jet of 20 mmol/L 2,3-butanedione monoxime (BDM) or 20 mumol/L blebbistatin. Sustained arrhythmias (>10 seconds) could be induced by stimulus trains for 7.5 seconds only with the BDM or blebbistatin jet (100 nmol/L isoproterenol, 1.0 mmol/L [Ca(2+)](o), 24 degrees C). During sustained arrhythmias, Ca(2+) surges preceded synchronous increases in [Ca(2+)](i), whereas the stoppage of the BDM jet made the Ca(2+) surges unclear and arrested sustained arrhythmias (n=6). With 200 nmol/L isoproterenol, 2.5 mmol/L [Ca(2+)](o), and the BDM jet, lengthening or shortening of the muscle during sustained arrhythmias accelerated or decelerated their cycle in both the absence (n=10) and presence (n=10) of 100 mumol/L streptomycin, a stretch-activated channel blocker, respectively. The maximum rate of force relaxation correlated inversely with the change in cycle lengths (n=14; P<0.01). Sustained arrhythmias with the BDM jet were significantly accelerated by 30 mumol/L SCH00013, a Ca(2+) sensitizer of myofilaments (n=10).These results suggest that nonuniformity of muscle contraction is an important determinant of the sustainability and frequency of triggered arrhythmias caused by the surge of Ca(2+) dissociated from myofilaments in cardiac muscle.
Randomized Trial of Laparoscopic-Assisted Resection of Colorectal Carcinoma: 3-Year Results of the UK MRC CLASICC Trial Group
Authors: David G. Jayne, Pierre J. Guillou, Helen Thorpe, Philip Quirke, Joanne Copeland, Adrian M.H. Smith, Richard M. Heath, Julia M. Brown
Journal: Journal of Clinical Oncology (2007)

The aim of the current study is to report the long-term outcomes after laparoscopic-assisted surgery compared with conventional open surgery within the context of the UK MRC CLASICC trial. Results from randomized trials have indicated that laparoscopic surgery for colon cancer is as effective as open surgery in the short term. Few data are available on rectal cancer, and long-term data on survival and recurrence are now required.The United Kingdom Medical Research Council Conventional versus Laparoscopic-Assisted Surgery in Colorectal Cancer (UK MRC CLASICC; clinical trials number ISRCTN 74883561) trial study comparing conventional versus laparoscopic-assisted surgery in patients with cancer of the colon and rectum. The randomization ratio was 2:1 in favor of laparoscopic surgery. Long-term outcomes (3-year overall survival [OS], disease-free survival [DFS], local recurrence, and quality of life [QoL]) have now been determined on an intention-to-treat basis.Seven hundred ninety-four patients were recruited (526 laparoscopic and 268 open). Overall, there were no differences in the long-term outcomes. The differences in survival rates were OS of 1.8% (95% CI, -5.2% to 8.8%; P = .55), DFS of -1.4% (95% CI, -9.5% to 6.7%; P = .70), local recurrence of -0.8% (95% CI, -5.7% to 4.2%; P = .76), and QoL (P > .01 for all scales). Higher positivity of the circumferential resection margin was reported after laparoscopic anterior resection (AR), but it did not translate into an increased incidence of local recurrence.Successful laparoscopic-assisted surgery for colon cancer is as effective as open surgery in terms of oncological outcomes and preservation of QoL. Long-term outcomes for patients with rectal cancer were similar in those undergoing abdominoperineal resection and AR, and support the continued use of laparoscopic surgery in these patients.
Systems-level approaches reveal conservation of trans-regulated genes in the rat and genetic determinants of blood pressure in humans
Authors: Sarah R. Langley, Leonardo Bottolo, Jaroslav Kunes, Josef Zicha, Vaclav Zidek, Norbert Hubner, Stuart A. Cook, Michal Pravenec, Timothy J. Aitman, Enrico Petretto
Journal: Cardiovascular Research (2012)

Human genome-wide association studies (GWAS) of hypertension identified only few susceptibility loci with large effect that were replicated across populations. The vast majority of genes detected by GWAS has small effect and the regulatory mechanisms through which these genetic variants cause disease remain mostly unclear. Here, we used comparative genomics between human and an established rat model of hypertension to explore the transcriptional mechanisms mediating the effect of genes identified in 15 hypertension GWAS. Time series analysis of radiotelemetric blood pressure (BP) was performed to assess 11 parameters of BP variation in recombinant inbred strains derived from the spontaneously hypertensive rat. BP data were integrated with ∼27 000 expression quantative trait loci (eQTLs) mapped across seven tissues, detecting >8000 significant associations between eQTL genes and BP variation in the rat. We then compiled a large catalogue of human genes from GWAS of hypertension and identified a subset of 2292 rat–human orthologous genes. Expression levels for 795 (34%) of these genes correlated with BP variation across rat tissues: 51 genes were cis-regulated, whereas 459 were trans-regulated and enriched for 'calcium signalling pathway' (P = 9.6 × 10−6) and 'ion channel' genes (P = 3.5 × 10−7), which are important determinants of hypertension. We identified 158 clusters of trans-eQTLs, annotated the underlying 'master regulator' genes and found significant over-representation in the human hypertension gene set (enrichment P = 5 × 10−4). We showed extensive conservation of trans-regulated genes and their master regulators between rat and human hypertension. These findings reveal that small-effect genes associated with hypertension by human GWAS are likely to exert their action through coordinate regulation of pathogenic pathways.
Prednisolone in the treatment of airflow obstruction in adults with cystic fibrosis.
Authors: C F Pantin, R J Stead, M E Hodson, J C Batten
Journal: Thorax (1986)

The effect of oral prednisolone on the lung function of 20 adult patients with cystic fibrosis who had severe stable airflow obstruction was assessed in a placebo controlled study, blind to the patients.Placebo tablets were followed by prednisolone given in a median dose of 0.48 mg/kg body weight/day (20 mg/day in 11 patients, 30 mg/day in nine patients), each for three weeks.No significant improvement was seen in lung function in the group after receiving prednisolone, and none of the individual patients had clinically useful improvements in lung function.Atopic subjects showed an improvement in evening recordings of peak expiratory flow rate (PEF) while taking prednisolone (p < 0.05).Significant deterioration in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) was seen after withdrawal of prednisolone.Two patients developed pneumothoraces while taking prednisolone.
Propranolol compared with propranolol plus isosorbide dinitrate in portal-hypertensive patients: Long-term hemodynamic and renal effects
Authors: Julio Vorobioff, Eduardo Picabea, Marcelo Gamen, Roberto Villavicencio, Juan Bordato, Fernando Bessone, Hugo Tanno, Jorge Palazzi, Hector Sarano, Luisa Pozzoli, Roberto Sanchez, Ricardo Giordano
Journal: Hepatology (1993)

The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
INTUSSUSCEPTION DUE TO POLYPUS
Authors: J. L. Stretton
Journal: BMJ (1908)

days.Tbese results scareely endorse the view so frequently advanced as to the great danger of operatiog between the second and fifth days.But even though all these cases recovered, yet the earlier the operation the better the recovery.In all the operations within twenty- four and in the majority of those wlthin forty-eight hours,.therecovery was exactly similar to that after an ts interval " operation, without any risk of a weak scar.In most of those on the tbird and fourth days drainage was neceesary, convalescence was more prolonged, and the chances of a weak scar greater.Of the nine deaths in the Ferles five had general perl- tonitis, two had diffuse peritonitis with gangrene of the caecum as welkas of the appendix, one a local abscess, and one a large abscess extending to the subpbrenic region.Sarely these fatalities may be justly ascribed to delay rather than to operation; the operation certainly failed to save, but It cannot be said to have materially hastened the inevitable end.The great reduction in the mortality after operations for acute appendicitis that has followed the policy of " inter- fering " at an earlier period poi'nts irre3tstibly to the con- clusion that were all cases submitted to operation in the early stages of the attack appendicitis would cease to be a fatal disease.
Imatinib mesylate (Gleevec®) in advanced breast cancer-expressing C-Kit or PDGFR-β: clinical activity and biological correlations
Authors: M. Cristofanilli, P. Morandi, S. Krishnamurthy, J.M. Reuben, B.-N. Lee, D. Francis, D.J. Booser, M.C. Green, B.K. Arun, L. Pusztai, A. Lopez, R. Islam, V. Valero, G.N. Hortobagyi
Journal: Annals of Oncology (2008)
Molecular Cues to Implantation
Authors: S. K. Dey, H. Lim, Sanjoy K. Das, Jeff Reese, B. C. Paria, Takiko Daikoku, Haibin Wang
Journal: Endocrine Reviews (2004)

Successful implantation is the result of reciprocal interactions between the implantation-competent blastocyst and receptive uterus. Although various cellular aspects and molecular pathways of this dialogue have been identified, a comprehensive understanding of the implantation process is still missing. The receptive state of the uterus, which lasts for a limited period, is defined as the time when the uterine environment is conducive to blastocyst acceptance and implantation. A better understanding of the molecular signals that regulate uterine receptivity and implantation competency of the blastocyst is of clinical relevance because unraveling the nature of these signals may lead to strategies to correct implantation failure and improve pregnancy rates. Gene expression studies and genetically engineered mouse models have provided valuable clues to the implantation process with respect to specific growth factors, cytokines, lipid mediators, adhesion molecules, and transcription factors. However, a staggering amount of information from microarray experiments is also being generated at a rapid pace. If properly annotated and explored, this information will expand our knowledge regarding yet-to-be-identified unique, complementary, and/or redundant molecular pathways in implantation. It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.
Immunoglobulin M and D antigen receptors are both capable of mediating B lymphocyte activation, deletion, or anergy after interaction with specific antigen.
Authors: R Brink, C C Goodnow, J Crosbie, E Adams, J Eris, D Y Mason, S B Hartley, A Basten
Journal: The Journal of Experimental Medicine (1992)

A series of immunoglobulin (Ig)-transgenic mice were generated to study the functional capabilities of the IgM and IgD classes of B lymphocyte antigen receptor in regulating both cellular development and responses to specific antigen. B cells from Ig-transgenic mice expressing either hen-egg lysozyme (HEL)-specific IgM or IgD alone were compared with B cells from mice that coexpressed IgM and IgD of the same anti-HEL specificity. In all three types of Ig-transgenic mice, conventional B cells specific for HEL exhibited exclusion of endogenous Ig expression and matured to populate the usual microenvironments in peripheral lymphoid tissues. These peripheral B cells could be stimulated by HEL through either IgM or IgD antigen receptors to generate T cell dependent antibody production in vivo or to enhance T cell independent proliferative responses to lipopolysaccharide in vitro. Conversely, when HEL was encountered in vivo as a self-antigen, B cells expressing HEL-specific IgM or IgD alone were both rendered tolerant. In each case this occurred by clonal anergy in response to soluble autologous HEL, and clonal deletion when HEL was recognized as a membrane-bound self-antigen. Taken together, these findings indicate that IgM and IgD antigen receptors expressed alone on conventional B cells can support normal differentiation, antigen-dependent activation, and induction of self-tolerance, the only overt difference lying in a greater degree of receptor downregulation for IgM relative to IgD after induction of clonal anergy by soluble HEL.
Ex vivo MR spectroscopic measure differentiates tumor from treatment effects in GBM
Authors: R. Srinivasan, J. J. Phillips, S. R. VandenBerg, M.-Y. C. Polley, G. Bourne, A. Au, A. Pirzkall, S. Cha, S. M. Chang, S. J. Nelson
Journal: Neuro-Oncology (2010)

The motivation of this study was to address the urgent clinical problem related to the inability of magnetic resonance (MR) imaging measures to differentiate tumor progression from treatment effects in patients with glioblastoma multiforme (GBM). While contrast enhancement on MR imaging (MRI) is routinely used for assessment of tumor burden, therapy response, and progression-free survival in GBM, it is well known that changes in enhancement following treatment are nonspecific to tumor. To address this issue, the objective of this study was to investigate whether MR spectroscopy can provide improved biomarker surrogates for tumor following treatment. High-resolution metabolic profiles of tissue samples obtained from patients with GBM were directly correlated with their pathological assessment to determine metabolic markers that correspond to pathological indications of tumor or treatment effects. Acquisition of tissue samples with image guidance enabled the association of ex vivo biochemical and pathological properties of the tissue samples with in vivo MR anatomical and structural properties derived from presurgical MR images. Using this approach, we found that metabolic concentration levels of [Myo-inositol/total choline (MCI)] in tissue samples are able to differentiate tumor from nontumor and treatment-induced reactive astrocytosis with high significance (P < .001) in newly diagnosed and recurrent GBM. The MCI index has a sensitivity of 93% to tumor in recurrent GBM and delineates the contribution of cellularity that originates from tumor and astrocytic proliferation following treatment. Low levels of MCI for tumor were associated with a reduced apparent diffusion coefficient and elevated choline-N-acetyl-aspartate index derived from in vivo MR images.
Systematic Review and Meta-analysis of Studies Reporting Oncologic Outcome After Robot-assisted Radical Prostatectomy
Authors: Giacomo Novara, Vincenzo Ficarra, Simone Mocellin, Thomas E. Ahlering, Peter R. Carroll, Markus Graefen, Giorgio Guazzoni, Mani Menon, Vipul R. Patel, Shahrokh F. Shariat, Ashutosh K. Tewari, Hendrik Van Poppel, Filiberto Zattoni, Francesco Montorsi, Alexandre Mottrie, Raymond C. Rosen, Timothy G. Wilson
Journal: European Urology (2012)