tbuckley/cabot-search huggingface dataset:
Evolution of legume seed storage proteins--a domain common to legumins and vicilins is duplicated in vicilins.
Authors: P E Gibbs, K B Strongin, A McPherson
Journal: Molecular Biology and Evolution (1989)

We examined the primary sequence of canavalin, the major storage protein of jack beans, and found that an ancient sequence duplication accounts for 80% of the amino acid residues. Evidence for such a duplication was also found in the orthologous proteins phaseolin and pea vicilin. This sequence duplication presumably accounts for a structural duplication in the canavalin monomer observed by crystallographic analysis. One copy of this repeat was found in a second storage-protein family, the legumins, where it encompasses almost the entire B-chain of the mature molecule. We propose that the vicilin and legumin families of legume seed proteins evolved from a common precursor, which consisted of one copy of the repeat in the vicilins.
Deformable Medical Image Registration: Setting the State of the Art with Discrete Methods
Authors: Ben Glocker, Aristeidis Sotiras, Nikos Komodakis, Nikos Paragios
Journal: Annual Review of Biomedical Engineering (2011)

This review introduces a novel deformable image registration paradigm that exploits Markov random field formulation and powerful discrete optimization algorithms. We express deformable registration as a minimal cost graph problem, where nodes correspond to the deformation grid, a node's connectivity corresponds to regularization constraints, and labels correspond to 3D deformations. To cope with both iconic and geometric (landmark-based) registration, we introduce two graphical models, one for each subproblem. The two graphs share interconnected variables, leading to a modular, powerful, and flexible formulation that can account for arbitrary image-matching criteria, various local deformation models, and regularization constraints. To cope with the corresponding optimization problem, we adopt two optimization strategies: a computationally efficient one and a tight relaxation alternative. Promising results demonstrate the potential of this approach. Discrete methods are an important new trend in medical image registration, as they provide several improvements over the more traditional continuous methods. This is illustrated with several key examples where the presented framework outperforms existing general-purpose registration methods in terms of both performance and computational complexity. Our methods become of particular interest in applications where computation time is a critical issue, as in intraoperative imaging, or where the huge variation in data demands complex and application-specific matching criteria, as in large-scale multimodal population studies. The proposed registration framework, along with a graphical interface and corresponding publications, is available for download for research purposes (for Windows and Linux platforms) from http://www.mrf-registration.net.
NCoR controls glioblastoma tumor cell characteristics
Authors: Nina Heldring, Ulrika Nyman, Peter Lönnerberg, Sofie Önnestam, Anna Herland, Johan Holmberg,, Ola Hermanson
Journal: Neuro-Oncology (2013)

We have previously shown that the transcriptional coregulator NCoR represses astrocytic differentiation of neural stem cells, suggesting that NCoR could be a plausible target for differentiation therapy of glioblastoma. To study a putative role for NCoR in regulating glioblastoma cell characteristics, we used RNA-mediated knockdown followed by analysis of gene expression, proliferation and cell growth, autophagy, invasiveness in vitro, and tumor formation in vitro and in vivo. We further performed chromatin immunoprecipitation of NCoR followed by genome-wide sequencing in the human glioblastoma cell line U87 in order to reveal NCoR-occupied loci. RNA knockdown of NCoR resulted in a moderate increase in differentiation accompanied by a significant decrease in proliferation in adherent U87 human glioblastoma cells. chromatin immunoprecipitation sequencing approach revealed alternative mechanisms underlying the decrease in proliferation, as NCoR was enriched at promoters of genes associated with autophagy such as ULK3. Indeed, signs of an autophagy response in adherent glioblastoma cells included an increased expression of autophagy genes, such as Beclin1, and increased lipidation and nuclear puncta of LC3. Intriguingly, in parallel to the effects in the adherent cells, NCoR knockdown resulted in a significant increase in anchorage-independent growth, and this glioblastoma cell population showed dramatic increases in invasive properties in vitro and tumor formation capacity in vitro and in vivo along with an increased proliferation rate. Our results unveil unexpected aspects of NCoR regulation of tumor characteristics in glioblastoma cells and highlight the need for caution when transposing developmental concepts directly to cancer therapy.
Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) for treatment of early-stage gastric diffuse large B-cell lymphoma
Authors: S. Wöhrer, A. Püspök, J. Drach, M. Hejna, A. Chott, M. Raderer
Journal: Annals of Oncology (2004)
Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study
Authors: A Pedersen
Journal: Gut (2003)

There may be a weak association between total alcohol intake and colorectal cancer but the effect of different types of alcohol and effect on colon subsites have not been investigated satisfactorily.To investigate the relationship between amount and type of alcohol and the risk of colon and rectal cancer.A population based cohort study with baseline assessment of weekly intake of beer, wine, and spirits, smoking habits, body mass index, educational level, and leisure time physical activity in Copenhagen, Denmark. The study included a random sample of 15 491 men and 13 641 women, aged 23-95 years. Incident cases of colorectal cancer were identified in the nationwide Danish Cancer Register.During a mean follow up of 14.7 years, we observed 411 colon cancers and 202 rectal cancers. We observed a dose-response relationship between alcohol and rectal cancer. Drinkers of more than 41 drinks a week had a relative risk of rectal cancer of 2.2 (95% confidence limits 1.0-4.6) compared with non-drinkers. Drinkers of more than 14 drinks of beer and spirits a week, but not wine, had a risk of 3.5 (1.8-6.9) of rectal cancer compared with non-drinkers, while those who drank the same amount of alcohol but including more than 30% of wine had a risk of 1.8 (1.0-3.2) of rectal cancer. No relation between alcohol and colon cancer was found when investigating the effects of total alcohol, beer, wine, and spirits, and percentage of wine of total alcohol intake.Alcohol intake is associated with a significantly increased risk of rectal cancer but the risk seems to be reduced when wine is included in the alcohol intake.
EphA2 Targeted Chemotherapy Using an Antibody Drug Conjugate in Endometrial Carcinoma
Authors: Jeong-Won Lee, Rebecca L. Stone, Sun Joo Lee, Eun Ji Nam, Ju-Won Roh, Alpa M. Nick, Hee-Dong Han, Mian M.K. Shahzad, Hye-Sun Kim, Lingegowda S. Mangala, Nicholas B. Jennings, Shenlan Mao, John Gooya, Dowdy Jackson, Robert L. Coleman, Anil K. Sood
Journal: Clinical Cancer Research (2010)

EphA2 overexpression is frequently observed in endometrial cancers and is predictive of poor clinical outcome. Here, we use an antibody drug conjugate (MEDI-547) composed of a fully human monoclonal antibody against both human and murine EphA2 (1C1) and the tubulin polymerization inhibitor monomethylauristatin F.EphA2 expression was examined in endometrial cancer cell lines by Western blot. Specificity of MEDI-547 was examined by antibody degradation and internalization assays. Viability and apoptosis were investigated in endometrial cancer cell lines and orthotopic tumor models.EphA2 was expressed in the Hec-1A and Ishikawa cells but was absent in the SPEC-2 cells. Antibody degradation and internalization assays showed that the antibody drug conjugate decreased EphA2 protein levels and was internalized in EphA2-positive cells (Hec-1A and Ishikawa). Moreover, in vitro cytotoxicity and apoptosis assays showed that the antibody drug conjugate decreased viability and increased apoptosis of Hec-1A and Ishikawa cells. In vivo therapy experiments in mouse orthotopic models with this antibody drug conjugate resulted in 86% to 88% growth inhibition (P < 0.001) in the orthotopic Hec-1A and Ishikawa models compared with controls. Moreover, the mice treated with this antibody drug conjugate had a lower incidence of distant metastasis compared with controls. The antitumor effects of the therapy were related to decreased proliferation and increased apoptosis of tumor and associated endothelial cells.The preclinical data for endometrial cancer treatment using MEDI-547 show substantial antitumor activity.
Empirical Evidence for Selective Reporting of Outcomes in Randomized Trials
Authors: An-Wen Chan, Asbjørn Hróbjartsson, Mette T. Haahr, Peter C. Gøtzsche, Douglas G. Altman
Journal: JAMA (2004)

Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.
LED Fluorescence Microscopy for the Diagnosis of Pulmonary Tuberculosis: A Multi-Country Cross-Sectional Evaluation
Authors: Luis Eduardo Cuevas, Najla Al-Sonboli, Lovett Lawson, Mohammed Ahmed Yassin, Isabel Arbide, Nasher Al-Aghbari, Jeevan Bahadur Sherchand, Amin Al-Absi, Emmanuel Nnamdi Emenyonu, Yared Merid, Mosis Ifenyi Okobi, Juliana Olubunmi Onuoha, Melkamsew Aschalew, Abraham Aseffa, Greg Harper, Rachel Mary Anderson de Cuevas, Sally Jane Theobald, Carl-Michael Nathanson, Jean Joly, Brian Faragher, Stephen Bertel Squire, Andrew Ramsay
Journal: PLoS Medicine (2011)

The diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection.Adults with cough ≥2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., "on the spot") the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%-76.5%) and 65.8% (348/529, 95% CI 61.6%-69.8%) sensitive (p<0.001) and 90.9% (1,660/1,826, 95% CI 89.5%-92.2%) and 98% (1,790/1,826, 95% CI 97.3%-98.6%) specific (p<0.001). Using three LED-FM or three ZN smears per patient was 77% (408/529, 95% CI 73.3%-80.6%) and 70.5% (373/529, 95% CI 66.4%-74.4%, p<0.001) sensitive and 88.1% (95% CI 86.5%-89.6%) and 96.5% (95% CI 96.8%-98.2%, p<0.001) specific. The sensitivity/specificity of ZN smear microscopy and LED-FM did not vary between SMS and SSM.LED-FM had higher sensitivity but, in this study, lower specificity than ZN smear microscopy for diagnosis of pulmonary TB. Performance was independent of the scheme used for collecting specimens. The introduction of LED-FM needs to be accompanied by appropriate training, quality management, and monitoring of performance in the field.Current Controlled Trials ISRCTN53339491. Please see later in the article for the Editors' Summary.
Long-Term Outcome and Quality of Life of Patients With Endometrial Carcinoma Treated With or Without Pelvic Radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) Trial
Authors: Remi A. Nout, Lonneke V. van de Poll-Franse, Marnix L.M. Lybeert, Carla C. Wárlám-Rodenhuis, Jan J. Jobsen, Jan Willem M. Mens, Ludy C.H.W. Lutgens, Betty Pras, Wim L.J. van Putten, Carien L. Creutzberg
Journal: Journal of Clinical Oncology (2011)

To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial.Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat.Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P < .001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P < .01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P < .001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and "role-physical" (P = .003).EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low- and intermediate-risk EC.
Environmental exposures and mutational patterns of cancer genomes
Authors: Gerd P Pfeifer
Journal: Genome Medicine (2010)

The etiology of most human cancers is unknown. Genetic inheritance and environmental factors are thought to have major roles, and for some types of cancer, exposure to carcinogens is a proven mechanism leading to tumorigenesis. Sequencing of entire cancer genomes has not only begun to provide clues regarding functionally relevant mutations, but has also paved the way towards understanding the initial exposures leading to DNA damage, repair and eventually to mutation of specific sequences within a cancer genome. Two recent studies of melanoma and small cell lung cancer exemplify what type of information can be gained from cancer genome sequencing.
Toward the identification of genetic determinants of breast cancer immune responsiveness
Authors: Ines Simeone, Wouter Hendrickx, Lance Miller, Halima Bensmail, Ena Wang, Francesco Marincola, Michele Ceccarelli, Davide Bedognetti
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Overlapping immune signatures are observed among cancers with a better prognostic connotation and those with an increased likelihood to respond to immunotherapeutic approaches [[1][1], [2][2]]. Such signatures qualitatively overlap with those detected during other conditions of
DISTRIBUTION OF BLOOD IN THE FUNCTIONAL KIDNEY
Authors: A. N. Weaver, C. T. McCarver, H. G. Swann
Journal: The Journal of Experimental Medicine (1956)

An attempt to measure the distribution of blood in the functional kidney of dogs was made. The method involved the injection of liquid latex rubber into the vascular system at physiologic pressures, fixation of the rubber in situ, and then, after corroding away all tissue, measurement of the volume of the rubber casts. The kidney contains, in its functionally distended state, 14 per cent blood. Of this, 4.5 per cent is apparently in the arteries and some 7 per cent in the veins. The functional engorgement of the cortical interlobular veins (about 4 per cent) is particularly striking, for they form a dense palisade of 40 to 300 micro vessels. These are not seen at the usual autopsy since they have drained out and collapsed. It is pointed out that attempts to describe the blood distribution in the kidney after it has been drained of blood are of dubious value. In the light of these data, also, the nature of the measurement of "intrarenal pressure," accomplished by inserting a needle into the renal parenchyma, may be better understood: it is suggested to be primarily a measure of interlobular venous pressure.
Endovascular Treatment of Abdominal Aortic Aneurysms
Authors: Gerald S. Treiman, Victor M. Bernhard, MD
Journal: Annual Review of Medicine (1998)

Abdominal aortic aneurysms (AAA) may now be treated by endovascular placement of an arterial graft. These grafts are inserted through the femoral artery and then secured to the aorta above and below the aneurysm. The procedure reduces the risk of many perioperative complications and reduces hospital costs and length of stay. Several FDA-approved clinical trials are currently in progress with a variety of different devices. None is available for general use at this time. Overall, more than 800 grafts have now been placed, with a primary success rate of greater than 80%. Several complications have been reported, but the incidence of complications has generally decreased as proficiency has improved. The most troublesome problem has been leak of blood around the graft with continued risk of aneurysm rupture; therefore, follow-up CT scans and clinical examinations are mandatory to allow for appropriate treatment. Future modifications of current devices and techniques for delivery can be expected to reduce the incidence of currently identified problems. Endovascular grafting for AAA offers important potential advantages over conventional repair and may become increasingly important in the management of patients who have an abdominal aortic aneurysm.
Preventing Ventilator-Associated Pneumonia
Authors: Naomi P. O’Grady, Patrick R. Murray, Nancy Ames
Journal: JAMA (2012)

Ventilator-associated pneumonia (VAP) is among the most common infections in patients requiring endotracheal tubes with mechanical ventilation. Ventilator-associated pneumonia is associated with increased hospital costs, a greater number of days in the intensive care unit, longer duration of mechanical ventilation, and higher mortality. Despite widely accepted recommendations for interventions designed to reduce rates of VAP, few studies have assessed the ability of these interventions to improve patient outcomes. As the understanding of VAP advances and new technologies to reduce VAP become available, studies should directly assess patient outcomes before the health care community implements specific prevention approaches in clinical practice.
Targeting Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Kinase in the Mutant (V600E) B-Raf Signaling Cascade Effectively Inhibits Melanoma Lung Metastases
Authors: Arati Sharma, Melissa A. Tran, Shile Liang, Arun K. Sharma, Shantu Amin, Charles D. Smith, Cheng Dong, Gavin P. Robertson
Journal: Cancer Research (2006)

Abstract Malignant melanoma has a high propensity for metastatic spread, making it the most deadly form of skin cancer. B-RAF has been identified as the most mutated gene in these invasive cells and therefore an attractive therapeutic target. However, for uncertain reasons, chemotherapy inhibiting B-Raf has not been clinically effective. This has raised questions whether this pathway is important in melanoma metastasis or whether targeting a protein other than B-Raf in the signaling cascade could more effectively inhibit this pathway to reduce lung metastases. Here, we investigated the role played by V600EB-Raf in melanoma metastasis and showed that targeting this signaling cascade significantly reduces lung metastases. Small interfering RNA (siRNA)–mediated inhibition was used in mice to reduce expression (activity) of each member of the signaling cascade and effects on metastasis development were measured. Targeting any member of the signaling cascade reduced metastasis but inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase (Mek) 1 and Mek 2 almost completely prevented lung tumor development. Mechanistically, metastatic inhibition was mediated through reduction of melanoma cell extravasation through the endothelium and decreased proliferative capacity. Targeting B-Raf with the pharmacologic inhibitor BAY 43-9006, which was found ineffective in clinical trials and seems to act primarily as an angiogenesis inhibitor, did not decrease metastasis, whereas inhibition of Mek using U0126 decreased cellular proliferative capacity, thereby effectively reducing number and size of lung metastases. In summary, this study provides a mechanistic basis for targeting Mek and not B-Raf in the mutant V600EB-Raf signaling cascade to inhibit melanoma metastases. (Cancer Res 2006; 66(16): 8200-9)