tbuckley/cabot-search huggingface dataset:
A hidden reservoir of integrative elements is the major source of recently acquired foreign genes and ORFans in archaeal and bacterial genomes
Authors: Diego Cortez, Patrick Forterre, Simonetta Gribaldo
Journal: Genome biology (2009)

Archaeal and bacterial genomes contain a number of genes of foreign origin that arose from recent horizontal gene transfer, but the role of integrative elements (IEs), such as viruses, plasmids, and transposable elements, in this process has not been extensively quantified. Moreover, it is not known whether IEs play an important role in the origin of ORFans (open reading frames without matches in current sequence databases), whose proportion remains stable despite the growing number of complete sequenced genomes.We have performed a large-scale survey of potential recently acquired IEs in 119 archaeal and bacterial genomes. We developed an accurate in silico Markov model-based strategy to identify clusters of genes that show atypical sequence composition (clusters of atypical genes or CAGs) and are thus likely to be recently integrated foreign elements, including IEs. Our method identified a high number of new CAGs. Probabilistic analysis of gene content indicates that 56% of these new CAGs are likely IEs, whereas only 7% likely originated via horizontal gene transfer from distant cellular sources. Thirty-four percent of CAGs remain unassigned, what may reflect a still poor sampling of IEs associated with bacterial and archaeal diversity. Moreover, our study contributes to the issue of the origin of ORFans, because 39% of these are found inside CAGs, many of which likely represent recently acquired IEs.Our results strongly indicate that archaeal and bacterial genomes contain an impressive proportion of recently acquired foreign genes (including ORFans) coming from a still largely unexplored reservoir of IEs.
Potentiation of Kinesin Spindle Protein Inhibitor–Induced Cell Death by Modulation of Mitochondrial and Death Receptor Apoptotic Pathways
Authors: Ulka Vijapurkar, Wei Wang, Ronald Herbst
Journal: Cancer Research (2007)

Abstract Targeting the mitotic motor kinesin kinesin spindle protein (KSP) is a new strategy for cancer therapy. We have examined the molecular events induced by KSP inhibition and explored possible mechanisms of resistance and sensitization of tumor cells to KSP inhibitors. We found that KSP inhibition induced cell death primarily via activation of the mitochondrial death pathway. In HeLa cells, inhibition of KSP by small-molecule inhibitor monastrol resulted in mitotic arrest and rapid caspase activation. BclXL phosphorylation and loss of mitochondrial membrane potential was detected before significant caspase activation, which was required to trigger the subsequent apoptotic pathway. In A549 cells, however, KSP inhibition did not induce mitochondrial damage, significant caspase activity, or cell death. A549 cells aberrantly exited mitosis, following a prolonged drug-induced arrest, and arrested in a G1-like state with 4N DNA content in a p53-dependent manner. Overexpression of BclXL provided a protective mechanism, and its depletion rescued the apoptotic response to monastrol. In addition, Fas receptor was up-regulated in A549 cells in response to monastrol. Treatment with Fas receptor agonists sensitized the cells to monastrol-induced cell death, following exit from mitosis. Thus, activation of the death receptor pathway offered another mechanism to enhance KSP inhibitor–induced apoptosis. This study has elucidated cellular responses induced by KSP inhibitors, and the results provide insights for a more effective cancer treatment with these agents. [Cancer Res 2007;67(1):237–45]
The complotype: dictating risk for inflammation and infection
Authors: Claire L. Harris, Meike Heurich, Santiago Rodriguez de Cordoba, B. Paul Morgan
Journal: Trends in Immunology (2012)

Complement is a key component of immune defence against infection; it potently drives inflammation at sites of pathology and is essential for killing of pathogens. Genetic linkage of common complement polymorphisms to disease has advanced the concept that subtle changes in complement activity significantly affect disease risk. Functional analyses of disease-linked polymorphic variants demonstrate that, although individual polymorphisms cause only small changes in activity, when combined, the aggregate effects are large. The inherited set of common variants, the complotype, thus has a major impact on susceptibility to inflammatory and infectious diseases. Assessing the complotype of an individual will aid prediction of disease risk and inform intervention to reduce or eliminate risk.
EFFECTIVE EXERCISE BASED TRAINING INTERVENTIONS TARGETING INJURY PREVENTION IN TEAM-BASED SPORTS: A SYSTEMATIC REVIEW
Authors: E O'Malley, J Murphy, C Gissane, U McCarthy-Persson, C Blake
Journal: British Journal of Sports Medicine (2014)

Background Exercise-based training is proposed to aid injury prevention through enhanced neuromuscular-control and muscle strength. Objective To assess the effects of exercise-based interventions on injury incidence in team sports. Design Systematic review. Setting 5 electronic databases were searched (12/01/13) returning 275 unique articles. Participants 23 randomised controlled trials (RCTs) involving 21,479 participants were included. Interventions Multifaceted exercise programmes were tested against controls (normal practice) in 12 studies, 7 studies used a balance board, 3 studies targeted hamstring strength and 1 study examined eccentric training of the Achilles and patellar tendons. Main outcome measurements RCTs reporting overall or lower-limb injury incidence were included. Methodological quality of each trial was assessed using a tool developed by the Cochrane Bone, Joint and Muscle Trauma group (Goldman and Jones 2010). Meta-analysis was performed on homogenous studies using RevMan 5.1 software. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using the Mantel-Haenszel method in a random effects model. Results Pooled-analysis of multifaceted exercise programmes demonstrated a reduction in overall (RR=0.65, 95% CI=0.44–0.96, P=.03), knee (RR=0.79, 95% CI=0.63–0.99, P=.04), ACL (RR=0.51, 95% CI=0.28–0.93, P=.03) and ankle injury risk (RR=0.72, 95% CI=0.58–0.90, P=.003). Balance board interventions were shown to reduce hamstring (RR=0.22, 95% CI=0.05–1.02, P=.05) and ankle injury (RR=0.64, 95% CI=0.49–0.83, P=.001). Hamstring muscle training had no significant effect (RR=0.46, 95% CI=0.19–1.11, P=.09). Eccentric training of the Achilles and patellar tendons demonstrated an increased injury risk (RR=2.5, 95% CI=1.35- 4.61, P=.003). Conclusions Exercise-based interventions can reduce injury risk in team sports. Strategies are required to translate this evidence into practice.
Endothelial Cell Apoptosis in Angiogenesis and Vessel Regression
Authors: Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation Research (2000)

Abstract —The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. In the past few years, compelling evidence accumulated that dysregulation of apoptosis can lead to embryonal death and is involved in the pathophysiology of various inflammatory and degenerative diseases. Specifically, the occurrence of endothelial cell apoptosis has deleterious effects on the development of the cardiovascular system leading to embryonal death. Moreover, endothelial cell apoptosis counteracts neovascularization in the adult organism. On the basis of these findings, one may consider the regulation of endothelial cell apoptosis as a potential therapeutic target. The induction of endothelial cell apoptosis may limit unwanted neovascularization of tumors. In contrast, the prevention of endothelial cell apoptosis may improve angiogenesis and vasculogenesis in patients with ischemia. The present work critically reviews the existing data that supports a role of endothelial cell apoptosis for vascular growth and remodeling and provides insights into the mechanisms and the potential therapeutic consequences.
VLDL, Apolipoproteins B, CIII, and E, and Risk of Recurrent Coronary Events in the Cholesterol and Recurrent Events (CARE) Trial
Authors: Frank M. Sacks, Petar Alaupovic, Lemuel A. Moye, Thomas G. Cole, Bruce Sussex, Meir J. Stampfer, Marc A. Pfeffer, Eugene Braunwald
Journal: Circulation (2000)

Background —Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. Methods and Results —We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL–apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P =0.04), apoCIII in VLDL+LDL (RR 2.3, P =0.04), and apoE in HDL (RR 1.8, P =0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P =0.03), was not related to coronary events (RR 1.3, P =0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. Conclusions —The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.
Inhaled colistin in elderly patients with bronchiectasis and chronic bronchial infection with pseudomonas
Authors: Eva Tabernero, Ramon Alkiza, Pilar Gil, Javier Garros, David Cantero, Juan L. Artola, Luciano Ramos
Journal: European Respiratory Journal (2012)

Bronchiectasis is the end result of several different illnesses and a frequent cause of admission in hospitals for elderly people and chronic diseases. Although many guidelines recommend treatment with inhaled antibiotics in non cystic fibrosis (CF) bronchiectasis in chronic bronchial infection with pseudomonas aeruginosa, there is limited evidence for elderly patients

Aims: To assess the effectiveness of inhaled colistin in elderly patients with non CF bronchiectasis and chronic bronchial pseudomonas infection

Methods : Prospective, controlled, randomized and open. We included patients with HRCT diagnosed bronchiectasis, after an acute exacerbation admission and appropriate antimicrobial therapy. We collected data on demographics, clinical and functional characteristics, admissions and sputum microbiology. We followed the patients for one year, evaluating microbiological results, functional tests, readmissions and exitus.

Results: We included 25 patients, 13 treated with inhaled colistin and 12 in control group. Four patients stopped the treatment because of adverse effects. Main results are shown in table 1

View this table:



Conclusions: Significant more patients in the treatment group achieved Pseudomonas eradication, but we could not demonstrate clinical or functional benefits in our elderly patients. These results may be due to small sample size.

Side effects were frequent.
Individualized, Non–Age-Based Glycemic Control in Elderly Veterans With Diabetes
Authors: Drew A. Helmer, Usha Sambamoorthi, Mangala Rajan, Chin-Lin Tseng, Leonard M. Pogach
Journal: Diabetes Care (2008)

To examine the role of age and endocrinology care in glycemic testing and control in elderly veterans with diabetes.In this retrospective study of Veterans Health Administration clinic users aged > or = 65 years with diabetes, we compared glycemic testing and poor glycemic control (A1C > 9%) between older (> or = 75 years) and younger (65-74 years) veterans in the year 2000.Without adjustment, rates for glycemic testing were 70.2% in older and 71.1% in younger veterans, and those for poor control were 9.4% in older and 12.8% in younger veterans. After adjustment, older veterans had 1.8% lower probability of glycemic testing and 2.9% lower probability of poor control than younger veterans. Endocrinology care was associated with a higher probability of both glycemic testing (9.7%) and poor control (1.0%), regardless of age.Glycemic testing and control and effect of endocrinology care were comparable in older and younger veterans with diabetes.
Novel techniques and targets in cardiovascular microRNA research
Authors: S. Dangwal, C. Bang, T. Thum
Journal: Cardiovascular Research (2011)

MicroRNAs (miRNAs) are highly conserved, tiny (∼22 nucleotides) non-coding RNAs that have emerged as potent regulators of mRNA translation. miRNAs exhibit fine-tuning of the control of proteins involved in cell signalling (AE) pathways and in vital cellular and developmental processes. miRNAs are expressed in cardiovascular tissues, and multiple functional aspects of miRNAs underscore their key role in cardiovascular (patho)physiology. The development and increasing use of novel molecular biology tools have contributed to the recent success in miRNA research. In the present review, we discuss current updates on important and novel miRNA techniques, including: (i) miRNA screening tools; (ii) bioanalytical target prediction tools; (iii) target validation tools; and (iv) manipulative miRNA expression tools. We also present an update about recently identified miRNA targets that play a key role in cardiovascular development and disorders.
KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival
Authors: Raheleh Hatami, Anieta M. Sieuwerts, Sudeh Izadmehr, Zhong Yao, Rui Fang Qiao, Luena Papa, Maxime P. Look, Marcel Smid, Jessica Ohlssen, Alice C. Levine, Doris Germain, David Burstein, Alexander Kirschenbaum, Analisa DiFeo, John A. Foekens, Goutham Narla
Journal: Science Translational Medicine (2013)

The KLF6-SV1 splice variant is associated with poor prognosis in early-stage human breast cancer and drives metastasis through the regulation of an EMT-like program in culture and in vivo.
Chemotherapy‐induced peripheral neurotoxicity: A critical analysis
Authors: Susanna B. Park, David Goldstein, Arun V. Krishnan, Cindy S‐Y Lin, Michael L. Friedlander, James Cassidy, Martin Koltzenburg, Matthew C. Kiernan
Journal: CA A Cancer Journal for Clinicians (2013)

With a 3‐fold increase in the number of cancer survivors noted since the 1970s, there are now over 28 million cancer survivors worldwide. Accordingly, there is a heightened awareness of long‐term toxicities and the impact on quality of life following treatment in cancer survivors. This review will address the increasing importance and challenge of chemotherapy‐induced neurotoxicity, with a focus on neuropathy associated with the treatment of breast cancer, colorectal cancer, testicular cancer, and hematological cancers. An overview of the diagnosis, symptomatology, and pathophysiology of chemotherapy‐induced peripheral neuropathy will be provided, with a critical analysis of assessment strategies, neuroprotective approaches, and potential treatments. The review will concentrate on neuropathy associated with taxanes, platinum compounds, vinca alkaloids, thalidomide, and bortezomib, providing clinical information specific to these chemotherapies. CA Cancer J Clin 2013;63:419‐437. © 2013 American Cancer Society, Inc.
CURRENT STATUS OF THE SURGICAL TREATMENT OF PATIENTS WITH CAROTID ARTERY DISEASE: The Surgical Management of Carotid Atherosclerosis
Authors: C. M. Wittgen, MD, D. C. Brewster, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Patients with carotid atherosclerotic disease present with a history of a neurologic event or with the presence of a bruit on physical examination. Recently, large randomized prospective studies have examined this group of patients to determine the optimal course of medical and surgical management. The data from these studies, together with the natural history of carotid disease and factors associated with stroke risk, are reviewed.
Development of a Suicide Gene as a Novel Approach to Killing <i>Mycobacterium tuberculosis</i>
Authors: WILLIAM N. ROM, TING-AN YIE, KAM-MENG TCHOU-WONG
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The increase in multidrug-resistant tuberculosis and high mortality among those co-infected with HIV-1 necessitates new therapeutic approaches directed at Mycobacterium tuberculosis. We hypothesized that a dominant-negative mutation in the DNA-dependent RNA polymerase gene would inhibit transcription of all genes by blocking access of the wild-type enzyme to promoters. An evolutionarily invariant lysine was substituted with arginine by site-directed mutagenesis in the rpoB gene. The dominant-negative rpoB gene product inhibited a transposon-derived kanamycin-resistance gene in both M. smegmatis and M. tuberculosis H37Rv, leading to growth inhibition of the mycobacteria on solid media containing kanamycin. The dominant-negative mutant rpoB gene is a potential suicide gene especially for the treatment of multidrug-resistant tuberculosis once a delivery strategy is also developed.
Dvl2 Promotes Intestinal Length and Neoplasia in the <i>Apc</i> <i>Min</i> Mouse Model for Colorectal Cancer
Authors: Ciara Metcalfe, Ashraf E.K. Ibrahim, Michael Graeb, Marc de la Roche, Thomas Schwarz-Romond, Marc Fiedler, Douglas J. Winton, Anthony Corfield, Mariann Bienz
Journal: Cancer Research (2010)

APC mutations cause activation of Wnt/beta-catenin signaling, which invariably leads to colorectal cancer. Similarly, overexpressed Dvl proteins are potent activators of beta-catenin signaling. Screening a large tissue microarray of different staged colorectal tumors by immunohistochemistry, we found that Dvl2 has a strong tendency to be overexpressed in colorectal adenomas and carcinomas, in parallel to nuclear beta-catenin and Axin2 (a universal transcriptional target of Wnt/beta-catenin signaling). Furthermore, deletion of Dvl2 reduced the intestinal tumor numbers in a dose-dependent way in the Apc(Min) model for colorectal cancer. Interestingly, the small intestines of Dvl2 mutants are shortened, reflecting in part a reduction of their crypt diameter and cell size. Consistent with this, mammalian target of rapamycin (mTOR) signaling is highly active in normal intestinal crypts in which Wnt/beta-catenin signaling is active, and activated mTOR signaling (as revealed by staining for phosphorylated 4E-BP1) serves as a diagnostic marker of Apc(Min) mutant adenomas. Inhibition of mTOR signaling in Apc(Min) mutant mice by RAD001 (everolimus) reduces their intestinal tumor load, similarly to Dvl2 deletion. mTOR signaling is also consistently active in human hyperplastic polyps and has a significant tendency for being active in adenomas and carcinomas. Our results implicate Dvl2 and mTOR in the progression of colorectal neoplasia and highlight their potential as therapeutic targets in colorectal cancer.
Early development of shared intentionality with peers
Authors: Celia A. Brownell, Sara Nichols, Margarita Svetlova
Journal: Behavioral and Brain Sciences (2005)

In their account of the origins of human collaborative abilities, Tomasello et al. rely heavily on reasoning and evidence from adult–child collaborations. Peer collaborations are not discussed, but early peer collaborations differ from early adult–child collaborations. Describing and explaining the similarities and differences in shared intentionality with peers and adults will bring us closer to understanding the developmental mechanisms.
Establishment and Validation of Circulating Tumor Cell–Based Prognostic Nomograms in First-Line Metastatic Breast Cancer Patients
Authors: Antonio Giordano, Brian L. Egleston, David Hajage, Joseph Bland, Gabriel N. Hortobagyi, James M. Reuben, Jean-Yves Pierga, Massimo Cristofanilli, Francois-Clement Bidard
Journal: Clinical Cancer Research (2013)

Circulating tumor cells (CTC) represent a new outcome-associated biomarker independent from known prognostic factors in metastatic breast cancer (MBC). The objective here was to develop and validate nomograms that combined baseline CTC counts and the other prognostic factors to assess the outcome of individual patients starting first-line treatment for MBC.We used a training set of 236 patients with MBCs starting a first-line treatment from the M.D. Anderson Cancer Center (Houston, TX) to establish nomograms that calculated the predicted probability of survival at different time points: 1, 2, and 5 years for overall survival (OS) and 6 months and 1 and 2 years for progression-free survival (PFS).The covariates computed in the model were age, disease subtype, visceral metastases, performance status, and CTC counts by CellSearch. Nomograms were independently validated with 210 patients with MBCs from the Institut Curie (Paris, France) who underwent first-line chemotherapy. The discriminatory ability and accuracy of the models were assessed using Harrell c-statistic and calibration plots at different time points in both training and validation datasets.Median follow-up was of 23 and 29 months in the MD Anderson and Institut Curie cohorts, respectively. Nomograms showed good c-statistics: 0.74 for OS and 0.65 for PFS and discriminated OS prediction at 1, 2, and 5 years, and PFS prediction at 6 months and 1 and 2 years.Nomograms, which relied on CTC counts as a continuous covariate, easily facilitated the use of a web-based tool for estimating survival, supporting treatment decisions and clinical trial stratification in first-line MBCs.
OVARIAN CYST COMPLICATING LABOUR
Authors: C. J. G. Taylor
Journal: BMJ (1924)

CASE iii.-Fall of ant Infantt frown a Height of 45 ft.writhout fi*jur y.A baby 11 months old was taken to the Royal Infirmarv haiving, it was stated, fallen from a fifth-story window.The infant suffered from shock, but the only injury that could be found was a slightly bruised buttock.She was detained for observation; all that was noticed was that instead of being a lively child she was very quiet.After three days she was discharged as no serious injury could be found.The absence of injury was so striking that it seemed probable that the history and the distance fallen had been much exaggerated.In view of this I visited the scene of the accident and interviewed the eye-witnesses.The mother stated that whilst she was working about the house the baby had crawled on to a low stool beside an open window, the lower edge of which was only about 2k feet from the floor.