tbuckley/cabot-search huggingface dataset:
Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors
Authors: Xuri Li, Marc Tjwa, Lieve Moons, Pierre Fons, Agnes Noel, Annelii Ny, Jian Min Zhou, Johan Lennartsson, Hong Li, Aernout Luttun, Annica Pontén, Laetitia Devy, Ann Bouché, Hideyasu Oh, Ann Manderveld, Silvia Blacher, David Communi, Pierre Savi, Françoise Bono, Mieke Dewerchin, Jean-Michel Foidart, Monica Autiero, Jean-Marc Herbert, Désiré Collen, Carl-Henrik Heldin, Ulf Eriksson, Peter Carmeliet
Journal: Journal of Clinical Investigation (2004)

The angiogenic mechanism and therapeutic potential of PDGF-CC, a recently discovered member of the VEGF/PDGF superfamily, remain incompletely characterized. Here we report that PDGF-CC mobilized endothelial progenitor cells in ischemic conditions; induced differentiation of bone marrow cells into ECs; and stimulated migration of ECs. Furthermore, PDGF-CC induced the differentiation of bone marrow cells into smooth muscle cells and stimulated their growth during vessel sprouting. Moreover, delivery of PDGF-CC enhanced postischemic revascularization of the heart and limb. Modulating the activity of PDGF-CC may provide novel opportunities for treating ischemic diseases.
Evaluation and Management of Laryngopharyngeal Reflux
Authors: Charles N. Ford
Journal: JAMA (2005)

Laryngopharyngeal reflux (LPR) is a major cause of laryngeal inflammation and presents with a constellation of symptoms different from classic gastroesophageal reflux disease.To provide a practical approach to evaluating and managing cases of LPR.The PubMed database and the Ovid Database of Systematic Reviews were systematically searched for laryngopharyngeal reflux, laryngopharyngeal reflux fundoplication, laryngopharyngeal reflux PPI treatment, and gastroesophageal reflux AND laryngitis. Pertinent subject matter journals and reference lists of key research articles were also hand-searched for articles relevant to the analysis.Reflux of gastric contents is a major cause of laryngeal pathology. The pathophysiology and symptom complex of LPR differs from gastroesophageal reflux disease. Laryngeal pathology results from small amounts of refluxate--typically occurring while upright during the daytime--causing damage to laryngeal tissues and producing localized symptoms. Unlike classic gastroesophageal reflux, LPR is not usually associated with esophagitis, heartburn, or complaints of regurgitation. There is no pathognomonic symptom or finding, but characteristic symptoms and laryngoscopic findings provide the basis for validated assessment instruments (the Reflux Symptom Index and Reflux Finding Score) useful in initial diagnosis. There are 3 approaches to confirming the diagnosis of LPR: (1) response of symptoms to behavioral and empirical medical treatment, (2) endoscopic observation of mucosal injury, and (3) demonstration of reflux events by impedance and pH-monitoring studies and barium swallow esophagram. While pH monitoring remains the standard for confirming the diagnosis of gastroesophageal reflux, the addition of multichannel intraluminal impedance technology improves diagnostic accuracy for describing LPR events. Ambulatory multichannel intraluminal impedance assessment allows for identification of gaseous as well as liquid refluxate and detection of nonacid reflux events that are likely significant in confirming LPR. Although some patients respond to conservative behavioral and medical management, as is the case with gastroesophageal reflux, most require more aggressive and prolonged treatment to achieve regression of symptoms and laryngeal tissue changes. Surgical intervention such as laparoscopic fundoplication is useful in selected recalcitrant cases with laxity of the gastroesophageal sphincter.Laryngopharyngeal reflux should be suspected when the history and laryngoscopy findings are suggestive of the diagnosis. Failure to respond to a 3-month trial of behavioral change and gastric acid suppression by adequate doses of proton pump inhibitor medication dictates need for confirmatory studies. Multichannel intraluminal impedance and pH-monitoring studies are most useful in confirming LPR and assessing the magnitude of the problem.
Intermittent Hypoxia-induced Changes in Tumor-associated Macrophages and Tumor Malignancy in a Mouse Model of Sleep Apnea
Authors: Isaac Almendros, Yang Wang, Lev Becker, Frances E. Lennon, Jiamao Zheng, Brittney R. Coats, Kelly S. Schoenfelt, Alba Carreras, Fahed Hakim, Shelley X. Zhang, Ramon Farré, David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

An increased cancer aggressiveness and mortality have been recently reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, enhances melanoma growth and metastasis in mice.
Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model
Authors: Liesbet Van Praet, Filip E Van den Bosch, Peggy Jacques, Philippe Carron, Lennart Jans, Roos Colman, Elien Glorieus, Harald Peeters, Herman Mielants, Martine De Vos, Claude Cuvelier, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To assess the rates and explore predictors of microscopic gut inflammation in a cohort of patients with axial and peripheral spondyloarthritis (SpA). <h3>Methods</h3> Ileocolonoscopy was performed in 65 patients with axial and peripheral SpA from the Gent Inflammatory Arthritis and spoNdylitis cohorT. Histopathological analysis and scoring were performed by an experienced pathologist. <h3>Results</h3> Overall, 46.2% of the patients with SpA showed microscopic gut inflammation. In axial SpA, the following parameters were independently associated with gut involvement: male sex (OR=8.9, p=0.035); high disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (OR=2.05, p=0.032); restricted spinal mobility measured by the Bath Ankylosing Spondylitis Metrology Index (OR=1.94, p=0.009); and younger age (OR=0.85, p=0.013). No clear association was found for human leucocyte antigen-B27 status, presence of peripheral arthritis, enthesitis, uveitis, psoriasis, intake of non-steroidal anti-inflammatory drugs and family history of SpA. The prevalence of gut inflammation in non-radiographic axial SpA and ankylosing spondylitis was comparable. <h3>Conclusions</h3> The prevalence of microscopic gut inflammation in SpA remains unaltered over time. Younger age (shorter symptom duration), progressive disease, male sex and higher disease activity are independently associated with microscopic gut inflammation in axial SpA.
Discordant Sexual Identity in Some Genetic Males with Cloacal Exstrophy Assigned to Female Sex at Birth
Authors: William G. Reiner, John P. Gearhart
Journal: New England Journal of Medicine (2004)

Cloacal exstrophy is a rare, complex defect of the entire pelvis and its contents that occurs during embryogenesis and is associated with severe phallic inadequacy or phallic absence in genetic males. For about 25 years, neonatal assignment to female sex has been advocated for affected males to overcome the issue of phallic inadequacy, but data on outcome remain sparse.We assessed all 16 genetic males in our cloacal-exstrophy clinic at the ages of 5 to 16 years. Fourteen underwent neonatal assignment to female sex socially, legally, and surgically; the parents of the remaining two refused to do so. Detailed questionnaires extensively evaluated the development of sexual role and identity, as defined by the subjects' persistent declarations of their sex.Eight of the 14 subjects assigned to female sex declared themselves male during the course of this study, whereas the 2 raised as males remained male. Subjects could be grouped according to their stated sexual identity. Five subjects were living as females; three were living with unclear sexual identity, although two of the three had declared themselves male; and eight were living as males, six of whom had reassigned themselves to male sex. All 16 subjects had moderate-to-marked interests and attitudes that were considered typical of males. Follow-up ranged from 34 to 98 months.Routine neonatal assignment of genetic males to female sex because of severe phallic inadequacy can result in unpredictable sexual identification. Clinical interventions in such children should be reexamined in the light of these findings.
Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study
Authors: Niall C. Tebbutt, Kate Wilson, Val J. Gebski, Michelle M. Cummins, Diana Zannino, Guy A. van Hazel, Bridget Robinson, Adam Broad, Vinod Ganju, Stephen P. Ackland, Garry Forgeson, David Cunningham, Mark P. Saunders, Martin R. Stockler, YuJo Chua, John R. Zalcberg, R. John Simes, Timothy J. Price
Journal: Journal of Clinical Oncology (2010)

To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial.Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL).Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups.Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.
Synopsis of the National Institute for Health and Clinical Excellence Guideline for Management of Transient Loss of Consciousness
Authors: Paul N. Cooper, Maggie Westby, David W. Pitcher, Ian Bullock
Journal: Annals of Internal Medicine (2011)

Description: Transient loss of consciousness (TLoC) is common and often leads to incorrect diagnosis, unnecessary investigation, or inappropriate choice of specialist referral. In August 2010, the National Institute for Health and Clinical Excellence published a guideline that addressed the initial assessment of and most appropriate specialist referral for persons who have experienced TLoC. The guideline focused on correct diagnosis and relevant specialist referral and did not make treatment recommendations. This synopsis describes the principal recommendations concerning assessment and referral of a patient with TLoC. Methods: The National Clinical Guideline Centre developed the guidelines by using the standard methodology of the National Institute for Health and Clinical Excellence. A multidisciplinary guideline panel generated review questions, discussed evidence, and formulated recommendations. The panel included a technical team from the National Clinical Guideline Centre, who reviewed and graded all relevant evidence identified from literature searches published in English up to November 2009 and performed health-economic modeling. Both guideline development and final modifications were informed by comments from stakeholders and the public. Recommendations: The panel made clear recommendations regarding the assessment of a person after TLoC, which emphasized the importance of clinical reasoning in diagnosis. Persons with uncomplicated faint, situational syncope, or orthostatic hypotension should receive electrocardiography but do not otherwise require immediate further investigation or specialist referral. Persons with features that suggest epilepsy should be referred for specialist neurologic assessment; brief seizure-like activity was recognized as a common occurrence during syncope that should not be regarded as indicating epilepsy. Persons with a suspected cardiac cause for TLoC or in whom TLoC is unexplained after initial assessment should receive specialist cardiovascular assessment. Guidance was provided on the appropriate choices of cardiovascular investigation, according to the presenting clinical circumstances.
Use of insertional inactivation to facilitate studies of biological properties of pneumococcal surface protein A (PspA).
Authors: L S McDaniel, J Yother, M Vijayakumar, L McGarry, W R Guild, D E Briles
Journal: The Journal of Experimental Medicine (1987)

PspA is a cell surface protein of Streptococcus pneumoniae that is present on a number of clinical isolates as well as the nonencapsulated laboratory strain Rx1. In a previous report we have shown that mAbs directed against PspA can protect mice from at least some of the pneumococcal strains bearing this protein. In our present report we have produced insertional inactivation mutants that lack PspA and have used these mutants to demonstrate that PspA can play a role in pneumococcal virulence and that anti-PspA immunity can lead to protection against pneumococcal infection. PspA- mutants were obtained using derivatives of plasmid pVA891 carrying chromosomal fragments from Rx1. From one of the mutants, we cloned a 550 bp fragment of the pneumococcal gene into pVA891 and transferred this chimeric plasmid, designated pKSD300, into Escherichia coli. After transformation of pKSD300 into Rx1, PspA production is not detected. In colony hybridization experiments, the 550 bp fragment hybridizes specifically to pneumococcal isolates in a pattern consistent with the hypothesis that the fragment is a portion of the pspA structural gene that is different from the portions coding for the antigenic determinants detected by mAbs Xi64 or Xi126. When X-linked immunodeficient (xid) CBA/N mice were immunized with wild-type Rx1, they were resistant to challenge with type 3 strain WU2. However, when these mice were immunized with a PspA- mutant of Rx1, they failed to survive the subsequent challenge, indicating that immunity to PspA can contribute to the resistance to pneumococcal infection. Using pKSD300 we insertionally inactivated pspA in D39, a virulent strain of S. pneumoniae. When injected intravenously there was a 10-fold greater reduction of the mutant pneumococci in the blood, as compared to the wild-type D39.
Health-Related Quality of Life Among Long-Term Rectal Cancer Survivors With an Ostomy: Manifestations by Sex
Authors: Robert S. Krouse, Lisa J. Herrinton, Marcia Grant, Christopher S. Wendel, Sylvan B. Green, M. Jane Mohler, Carol M. Baldwin, Carmit K. McMullen, Susan M. Rawl, Eric Matayoshi, Stephen Joel Coons, Mark C. Hornbrook
Journal: Journal of Clinical Oncology (2009)

Purpose Intestinal stomas can pose significant challenges for long-term (≥ 5 years) rectal cancer (RC) survivors. Specifying common challenges and sociodemographic or clinical differences will further the development of tailored interventions to improve health-related quality of life (HRQOL). Patients and Methods This was a matched cross-sectional study of long-term RC survivors conducted in three Kaiser Permanente regions. The mailed questionnaire included the modified City of Hope Quality of Life-Ostomy (mCOH-QOL-Ostomy) and Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2). Groups surveyed were permanent ostomates (cases) and those who did not require an ostomy (controls). RC survivors were matched on sex, age, and time since diagnosis. Comparisons between groups used regression analysis with adjustment for age, comorbidity score, history of radiation therapy, income, and work status. Results Response rate was 54% (491 of 909). Cases and controls had similar demographic characteristics. On the basis of the mCOH-QOL-Ostomy, both male and female cases had significantly worse social well-being compared with controls, while only female cases reported significantly worse overall HRQOL and psychological well-being. For younger females (&lt; age 75 years), ostomy had a greater impact on physical well-being compared with older females. Based on the SF-36v2, statistically significant and meaningful differences between female cases and controls were observed for seven of the eight scales and on the physical and mental component summary scores. Conclusion Men and women report a different profile of challenges, suggesting the need for targeted or sex-specific interventions to improve HRQOL in this population. This may include focus on physical HRQOL for female ostomy survivors younger than age 75.
Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009
Authors: Sung-Yun Pai, Brent R. Logan, Linda M. Griffith, Rebecca H. Buckley, Roberta E. Parrott, Christopher C. Dvorak, Neena Kapoor, Imelda C. Hanson, Alexandra H. Filipovich, Soma Jyonouchi, Kathleen E. Sullivan, Trudy N. Small, Lauri Burroughs, Suzanne Skoda-Smith, Ann E. Haight, Audrey Grizzle, Michael A. Pulsipher, Ka Wah Chan, Ramsay L. Fuleihan, Elie Haddad, Brett Loechelt, Victor M. Aquino, Alfred Gillio, Jeffrey Davis, Alan Knutsen, Angela R. Smith, Theodore B. Moore, Marlis L. Schroeder, Frederick D. Goldman, James A. Connelly, Matthew H. Porteus, Qun Xiang, William T. Shearer, Thomas A. Fleisher, Donald B. Kohn, Jennifer M. Puck, Luigi D. Notarangelo, Morton J. Cowan, Richard J. O'Reilly
Journal: New England Journal of Medicine (2014)

The Primary Immune Deficiency Treatment Consortium was formed to analyze the results of hematopoietic-cell transplantation in children with severe combined immunodeficiency (SCID) and other primary immunodeficiencies. Factors associated with a good transplantation outcome need to be identified in order to design safer and more effective curative therapy, particularly for children with SCID diagnosed at birth.
P57 The London TB Metrics: are targets achievable in a local district hospital clinic?
Authors: L. S. C. Lok, L. Ridge, J. Barrett, D. J. F. Mack, D. D. Creer
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Tuberculosis (TB) has re-emerged as an important public health problem in the UK. Subsequent to the publication of ‘Stopping Tuberculosis in England: An Action Plan from the Chief Medical Officer’ in 2004, the London TB Metrics was produced, against which the performance of local TB services can be measured. This audit recorded relevant aspects of diagnosis and management of all adult TB patients in a local district hospital TB clinic, and compared them against the Metric targets. <h3>Methods</h3> Eight of the nine Metric indices were selected (neonatal BCG vaccination coverage excluded). Data were collected on all adult patients seen in an outpatient TB clinic in 2008 and compared against targets set in the London TB Metrics. <h3>Results</h3> 73 adults (35 males, 38 females) were diagnosed, of which 38 (49.4%) were pulmonary cases. 69 patients (94.5%) were offered an HIV test; 63 patients attended for testing, with two patients testing positive for HIV. Abstract P57 Table 1 summarises results achieved. <h3>Discussion</h3> We have audited performance of a local TB clinic against targets set in the London TB Metrics. Achieving a microbiological diagnosis in 65% is difficult as patients are often already on treatment before referred into the service. Changes were instituted in laboratory workflow patterns to improve sputum smear result availability within one working day, increasing to 93.8% in the first 2 months of 2010. <h3>Conclusion</h3> The London TB Metrics targets are achievable (seven of eight targets met) and provide an audit tool that may facilitate improvements in the standard of TB care.
Habitat Variability Correlates with Duplicate Content of Drosophila Genomes
Authors: Takashi Makino, Masakado Kawata
Journal: Molecular Biology and Evolution (2012)

The factors limiting the habitat range of species are crucial in understanding their biodiversity and response to environmental change. Yet the genetic and genomic architectures that produce genetic variation to enable environmental adaptation have remained poorly understood. Here we show that the proportion of duplicated genes (PD) in the whole genomes of fully sequenced Drosophila species is significantly correlated with environmental variability within the habitats measured by the climatic envelope and habitat diversity. Furthermore, species with a low PD tend to lose the duplicated genes owing to their faster evolution. These results indicate that the rapid relaxation of functional constraints on duplicated genes resulted in a low PD for species with lower habitat diversity, and suggest that the maintenance of duplicated genes gives organisms an ecological advantage during evolution. We therefore propose that the PD in a genome is related to adaptation to environmental variation.
Regulation of Vascular Tone
Authors: Gabor Kaley
Journal: Circulation Research (2000)

ayliss 1 first suggested that distention (stretch) of the vascular wall, elicited by increases in intravascular pressure, acts as a facilitating stimulus on the vascular smooth muscle (VSM) to intensify its activity, eliciting constriction of blood vessels.Since this original hypothesis was offered, it has been recognized that this pressuresensitive response, a constriction to elevation and a dilation to reduction of transmural pressure, originates from the smooth muscle layer of blood vessels and is independent of neural, hormonal, and metabolic influences. 2 Although it is most pronounced in arterioles, it can also be demonstrated frequently in all types of blood vessels and lymphatics.The myogenic response contributes to autoregulation of blood flow and is believed to be one of the primary mechanisms responsible for the basal tone of small blood vessels.Consequently, it also influences capillary hydrostatic pressure.Although there is no general agreement as to the nature of the transduction mechanisms mediating the myogenic response, there is a consensus that stretch of the VSM membrane results in membrane depolarization, leading to augmented Ca 2ϩ influx through increased voltage-gated Ca 2ϩ channel activity and contraction of VSM via Ca 2ϩ -calmodulin-induced myosin light chain kinase phosphorylation.Among the mediators that have been proposed to be involved in the mechanotransduction of the stretch signal are activation of phospholipase C and A 2 , the adenylate cyclase/cAMP/ protein kinase A signaling pathway, protein kinase C-and tyrosine kinase-mediated mechanisms, and a variety of ion channels, as well as integrins and elements of the cytoskeleton of VSM. 3,4n this issue of Circulation Research, Gebremedhin et al, 5 in continuation of a long series of studies, report evidence of a role for 20-HETE in the myogenic response of cerebral arterioles.These authors have shown previously that 20-HETE, a nonendothelium-derived product of the cytochrome P450 4A pathway of arachidonic acid metabolism, 6 constricts arterioles at a threshold concentration of Ͻ10 -10 mol/L and that blockade of the endogenous formation of 20-HETE in VSM cells activates large-conductance calcium-activated potassium (K Ca ) channels, an activation that is reversed by